CPG Management of Atrial Fibrillation PDF

MOH/P/PAK/259.
12(GU)
STATEMENT OF INTENT
This guideline is meant to be a guide for clinical practice, based on the best
available evidence at the time of development. Adherence to this guideline may
not necessarily guarantee the best outcome in every case. Every health care
provider is responsible for the management of his/her unique patient based on
the clinical picture presented by the patient and the management options
available locally.
This guideline was issued in 2011 and will be reviewed in 2016 or sooner if
new evidence becomes available
CPG Secretariat
c/o Health Technology Assessment Unit
Medical Development Division
Ministry of Health Malaysia
4th floor, Block E1, Parcel E
62590, Putrajaya.
Electronic version available on the following website:
http://www.malaysianheart.org
http:// www.moh.gov.my
http://www.acadmed.org.my
i
ii
FOREWORD BY PRESIDENT OF NATIONAL HEART ASSOCIATION
OF MALAYSIA (NHAM)
THE PUBLICATION of the Clinical Practice Guidelines for Atrial Fibrillation

marked a milestone in the evolution of clinical practice guidelines and the delivery
of care in cardiology. Specifically, these guidelines assist physicians in clinical
decision making by describing a range of generally acceptable approaches
for the diagnosis, management, and prevention of AF. Clinical Issues eg: AF
assessment, best treatment strategy for acute AF & reduce risk of adverse
outcomes from AF, best long term treatment strategy, management of AF in
specific special groups have been addressed in the CPG.
In a broader sense, these guidelines emphasized that AF is a worldwide public

health problem with increasing incidence and prevalence, high cost, and poor
outcomes. Importantly, this AF CPG has provided the framework for a public
health approach to improve the quality of care and outcomes of all individuals with
AF. This is a major paradigm shift from the focus on AF treatment and care that
has dominated the practice to IMPORTANT STRATEGIES eg: risk stratification,
appropriate antithrombotic therapy, safety consideration of antiarrhythmic agents
emphasized in rhythm strategy.
This latest version has undergone extensive revision in response to comments

during the public review. While considerable effort has gone into their preparation
over the past 2 years, and every attention has been paid to their detail and scientific
rigor, no set of guidelines, no matter how well developed, achieves its purpose
unless it is implemented and translated into clinical practice. Implementation is an
integral component of the process and accounts for the success of the guidelines.
The Work Group is now developing implementation tools essential to the success
of this AFCPG.
In a voluntary and multidisciplinary undertaking of this magnitude, many individuals

make contributions to the final product now in your hands. It is impossible to
acknowledge them individually here, but to each and every one of them we extend
our sincerest appreciation, especially to the members of the Writing Panel, an
effort subsequently reinforced by the review of these final guidelines by the
external reviewers. Thank you one and all for Making Lives Better for patients with
AF throughout Malaysia. A special debt of gratitude is due to the members of the
Work Group, their chair, Dr Ahmad Nizar. It is their commitment and dedication
that has made it all possible.
Professor Dr. Sim Kui Hian FNHAM

NHAM President
iii
ABOUT THE GUIDELINE
GUIDELINE DEVELOPMENT PROCESS
This is the first Clinical Practice Guideline (CPG) for Atrial Fibrillation (AF). A
committee was appointed by the National Heart Association of Malaysia (NHAM),
Ministry of Health (MOH) and the Academy of Medicine Malaysia (AMM) to draw up
this CPG. It comprises of sixteen members including cardiologists, a neurologist,
a haematologist, a cardiac surgeon, an obstetrician, a gynaecologist, general
physicians, an intensivist, a family medicine specialist and an emergency medicine
specialist from the government, private sector and the public universities.
Objectives
This CPG is intended to assist health care providers in clinical decision making
by describing a range of generally acceptable approaches for the diagnosis,
management, and prevention of AF.
Rigour of Development
Evidence was obtained by systematic review of current medical literature on Atrial

Fibrillation using the usual search engines – Guidelines International Network
(G-I-N), Pubmed/Medline, Cochrane Database of Systemic Reviews (CDSR),
Database of Abstracts of Reviews of Effectiveness (DARE), Journal full text via
OVID search engine, International Health Technology Assessment websites (refer
to Appendix A for Search Terms). In addition, the reference lists of all retrieved
articles were searched to identify relevant studies. Search was limited to literature
published in English. All searches were officially conducted between 15 January
2010 and 10 December 2011. We suggest that future CPG updates will consider
evidence published after this cut-off date. The details of the search strategy can
be obtained upon request from the CPG secretariat.
Reference was also made to other guidelines on Atrial Fibrillation, Guidelines

for the Management of Atrial Fibrillation published by The Task Force for the
Management of Atrial Fibrillation of the European Society of Cardiology (ESC)
2010, The National Institute for Health and Clinical Excellence Atrial Fibrillation
Guideline 2006, Evidence-based Best Practice Guideline of New Zealand on
Atrial Fibrillation 2005 and the ACC/AHA/ESC Guidelines for the Management
of Patients With Atrial Fibrillation 2006 were also studied. These CPGs were
evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE)
prior being used as references.
Forty-three clinical questions were developed and divided into eight major sections
and members of the development panel were assigned individual questions within
these subtopics (refer to Appendix B for Clinical Questions). The group members
met a total 18 times throughout the development of the guideline. All retrieved
literature were appraised by at least two members and subsequently presented
for discussion during development group meetings.
iv
All statements and recommendations formulated were agreed collectively by
members of the Development Panel. Where the evidence was insufficient the
recommendations were derived by consensus of the Panel. These CPG are
based largely on the findings of systematic reviews, meta-analyses and clinical
trials, with local practices taken into consideration.
On completion, the draft guidelines was sent for review by external reviewers. It
was posted on the Ministry of Health of Malaysia official website for comment and
feedback from any interested parties. These guidelines had also been presented
to the Technical Advisory Committee for CPG, and the HTA and CPG Council,
Ministry of Health of Malaysia for review and approval.
The level of recommendation and the grading of evidence used in this guideline
were adapted from the American Heart Association and the European Society of
Cardiology (AHA/ESC) and outlined on page xi. In the text, this is written in black
and boxed on the left hand margin.
Sources of Funding
Sanofi Aventis (M) Sdn. Bhd. supported the development of the CPG on
Management of Atrial Fibrillation financially. However, the views of the funding
body have not influenced the content of the guideline.
Disclosure statement
The development panel members had completed disclosure forms. None held
shares in pharmaceutical firms or acted as consultants to such firms. (Details are
available upon request from the CPG Secretariat)
Clinical Issues Addressed
1. How do you assess a patient suspected of having atrial fibrillation?

2. What is the best strategy to treat patients with atrial fibrillation in the acute
setting?
3. What is the best strategy to reduce the risk of adverse outcomes from atrial
fibrillation?
4. What is the best long-term management strategy?
5. How to manage atrial fibrillation in specific special groups?  
Target Group
This CPG is directed at all healthcare providers treating patients with AF –

allied professionals, family and general physicians, medical officers, emergency
physicians, intensivists and cardiologists.
Target Population
It is developed to assist clinical decision making for all adults and pregnant
women with AF.
v
Period of Validity of the Guidelines
This guideline needs to be revised at least every 5 years to keep abreast with
recent developments and knowledge.
Implementation of the Guidelines
To ensure successful implementation of this CPG we suggest:
1. Constant checks and feedback on whether the guideline is relevant.
2. Identify implementation leaders
Identification of multiple leaders to share the implementation work and ensure

seamless care. These leaders are likely to be prominent figures who will
champion the guideline and inspire others.
3. Identify an implementation group
Support from medical associations such as the Private Medical Practitioners

Society (PMPS), Society of Pacing and Electrophysiology (SOPACE)
and Malaysian Medical Association (MMA) will help dissemination of the
guidelines.
4. Carrying out a baseline assessment
This involves comparing current practice with the recommendations. The audit
criteria will help this baseline assessment.
5. Developing an action plan
The baseline assessment will have identified which recommendations are

not currently being carried out. These recommendations could be put into an
action plan.
6. Key areas for implementation
We have identified several goals for implementation based on the key priorities
for implementation identified in the guideline
vi
GUIDELINE WORKING GROUP
Chairperson
Dr Ahmad Nizar b Jamaluddin
Consultant Cardiologist & Electrophysiologist
Sime Darby Medical Centre
Selangor
Dr Anita bt Alias
Intensivist
Hospital Melaka
Melaka
Datuk Dr Hj Azhari b Rosman,

Consultant Cardiologist & Electrophysiologist
National Heart Institute
Kuala Lumpur
Dato’ Dr Chang Kian Meng

Consultant Heamatologist & Head of Department
Department of Haematology
Hospital Ampang
Kuala Lumpur
Dr Ernest Ng Wee Oon

Consultant Cardiologist and Electrophysiologist
Pantai Hospital KL
Kuala Lumpur
Dr Hashim b Tahir
Consultant Obstetrician & Gynaecologist
Universiti Technologi MARA
Selangor
Associate Professor Dr Imran b Zainal Abidin

Associate Professor of Medicine & Consultant Cardiologist
University Malaya Medical Centre
Kuala Lumpur
Dr Jeswant Dillon
Consultant Cardiothoracic Surgeon
National Heart Institute
Kuala Lumpur
vii
Professor Dato’ Dr Khalid b Haji Yusoff,
Professor of Medicine and Senior Consultant Cardiologist
Universiti Teknologi MARA
Selangor
Dr Lai Voon Ming

Consultant Cardiologist and Electrophysiologist
Sri Kota Medical Centre
Selangor
Dr Ngau Yen Yew

Consultant Physician
Hospital Kuala Lumpur
Kuala Lumpur
Dato’ Dr Omar b Ismail,

Consultant Cardiologist & Head of Department
Department of Cardiology
Hospital Pulau Pinang
Prof. Madya Dr Oteh b Maskon

Consultant Cardiologist & Head of Department
Hospital Universiti Kebangsaan Malaysia
Kuala Lumpur
Datuk Dr Raihanah bt Abdul Khalid

Consultant Neurologist
Pantai Hospital KL
Kuala Lumpur
Dr Ridzuan b Dato Mohd Isa

Emergency Medicine Specialist & Head of Department
Department of Accident & Emergency
Hospital Ampang
Kuala Lumpur
Dr V Paranthaman
Family Medicine Specialist & Head of Department
Klinik Kesihatan Jelapang
Perak
viii
EXTERNAL REVIEWERS
1) Dato’ Dr Ravindran Jegasothy

Senior Consultant & Head of Department
Obstetrics & Gynaecology
Hospital Kuala Lumpur
2) Datuk Dr Razali b Omar

Deputy Head, Consultant Cardiologist & Electrophysiologist
Director of Clinical Electrophysiology & Pacemaker Service
3) Professor Dr Sim Kui Hian

Visiting Senior Consultant Cardiologist
Sarawak General Hospital Heart Centre
Adjunct Professor
Faculty of Medicine & Health Sciences
University Malaysia Sarawak (UNIMAS)
4) Dato’ Dr. Sree Raman

Senior Consultant Physician
Hospital Tuanku Jaafar
Seremban
5) Dr Tai Li Ling
Consultant Intensivist
Department of Anaesthesia and Intensive Care
Hospital Kuala Lumpur.
ix
SUMMARY
KEY MESSAGES
1 An electrocardiogram (ECG) should be performed in all patients, whether

symptomatic or not, in whom AF is suspected because an irregular pulse
has been detected.
2 The stroke risk stratification algorithms, CHADS2 and CHA2DS2VASc,

should be used in patients with AF to assess their risk of stroke and
thrombo-embolism, while the HAS-BLED score should be used to assess
their risk of bleeding.
3 Antithrombotic therapy should be based upon the absolute risks of stroke/

thrombo-embolism and bleeding, and the relative risk and benet for a
given patient.
4 When choosing either an initial rate-control or rhythm-control strategy, the

indications for each option should not be regarded as mutually exclusive
and the potential advantages and disadvantages of each strategy should be
explained to patients before agreeing which to adopt. Any comorbidities that
might indicate one approach rather than the other should be taken into
account . Irrespective of whether a rate-control or a rhythm-control strategy
is adopted in patients with persistent or paroxysmal AF, appropriate
antithrombotic therapy should be used.
5 When choosing an antiarrhythmic agent for rhythm control strategy, safety

rather than efficacy considerations should primarily guide the choice of
antiarrhythmic agent.
6 In patients with permanent AF, who need treatment for rate control, beta-
blockers or rate-limiting calcium antagonists should be the preferred initial
monotherapy in all patients while digoxin should only be considered as
monotherapy in predominantly sedentary patients.
x
The management cascade for patients with AF. ACEI = angiotensin-converting enzyme inhibitor; AF = atrial
fibrillation; ARB = angiotensin receptor blocker; PUFA = polyunsaturated fatty acid; TE = thrombo-embolism.
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart
Journal 2010; doi:10.1093/eurheartj/ehq278)
xi
<<ATRIAL
<<ATRIAL
FIBRILLATION
FIBRILLATION
MANAGEMENT
MANAGEMENT
CASCADE>>
CASCADE>>
Grading
Grading
System
System
The
The
format
format
used
used
forfor
Classification
Classification
of of
Recommendations
Recommendations andand
Level
Level
of of
Evidence
Evidence
was
was
adapted
adapted
from
from
thethe
American
American Heart
Heart
Association
Association
andand
thethe
European
EuropeanSociety
Society
of of
Cardiology.
Cardiology.
GRADES
GRADES
OFOF
RECOMMENDATIONS
RECOMMENDATIONS
AND
AND
LEVELS
LEVELS
OFOF
EVIDENCE
EVIDENCE
GRADES OFOF
GRADES RECOMMENDATION
RECOMMENDATION
Conditions
Conditions forfor which
which there
there is evidence
is evidence and/or
and/or general
general agreement
agreement
I I thatthat a given
a given procedure/therapy
procedure/therapy is beneficial,
is beneficial, useful
useful and/or
and/or
effective.
effective.
Conditions forfor
Conditions which there
which is conflicting
there evidence
is conflicting and/or
evidence and/or
II II divergence
divergenceof opinion about
of opinion aboutthethe
usefulness/efficacy of aof a
usefulness/efficacy
procedure/therapy.
procedure/therapy.
II-aII-a Weight
Weightof evidence/opinion is in
of evidence/opinion is favor of its
in favor usefulness/efficacy.
of its usefulness/efficacy.
II-bII-b Usefulness/efficacy is less

Usefulness/efficacy well
is less established
well by by
established evidence/opinion
evidence/opinion
Conditions
Conditionsforfor
which there
which is evidence
there is evidenceand/or general
and/or agreement
general agreement
III III thatthat
a procedure/therapy
a procedure/therapyis not useful/effective
is not andand
useful/effective in some
in some
cases may
cases maybe be
harmful.
harmful.
LEVELS OFOF
LEVELS EVIDENCE
EVIDENCE
Data derived
Data from
derived multiple
from randomised
multiple randomised clinical trials
clinical or meta
trials or meta
A A
analyses
analyses
Data derived
Data from
derived a single
from randomised
a single randomised clinical trialtrial
clinical or large nonnon
or large
B B
randomised
randomised studies
studies
Only consensus
Only consensusof opinions of experts,
of opinions case
of experts, casestudies
studies or standard
or standard
C C
of care
of care
Adapted from the American Heart Association/American College of Cardiology (AHA/

ACC) and the European Society of Cardiology (ESC)
xii
TABLE OF CONTENTS
Statement of Intent
Foreword
About the Guideline
Guideline Development Process
Guideline Working Group
External Reviewer
Summary
Key Messages
Atrial Fibrillation Management Cascade
Grading System
Table of Content
I. Introduction
1.1 Definition
1.2 Types of Atrial Fibrillation
1.3 AF Natural Time Course
1.4 Epidemiology and Prognosis
2. Pathophysiology
2.1. Clinical Aspects
2.1.1. Causes and Associated Conditions
3. Initial Management
3.1. Clinical History and Physical Examination and Investigations
3.1.1. Detection
3.1.1.1. Electrocardiogram
3.1 Diagnostic Evaluation
3.2 Echocardiogram
3.3 Clinical Follow-up
4 Management Principles
4.1 General Principles
4.2 Thromboembolic Prophylaxis
4.3 Heart Rate vs Rhythm Control
5 Management – Acute-onset AF
5.1 Acute AF In Hemodynamically Unstable Patients
5.1.1 Acute Rate Control
5.1.2 Pharmacological Cardioversion
5.1.2.1 Pill-in-the-pocket Approach
5.1.3 Direct Current Cardioversion
5.1.3.1 Procedure
5.1.3.2 Complications
5.1.3.3 Cardioversion In Patients With Implanted
Pacemakers And Defibrillators
5.1.3.4 Recurrence After Cardioversion
5.1.4 Antithrombotic Therapy For Acute-onset AF
6 Management - Prevention of Thromboembolism
xiii
6.1 Risk Stratification For Stroke
6.2 Strategies for Thromboembolic Prophylaxis
6.3 Antithrombotic Therapy
6.3.1 Anticoagulation With Vitamin K Antagonists
6.3.2 Optimal International Normalized Ratio
6.3.2.1 Point-of-care testing and self-monitoring of
anticoagulation
6.3.3 Anticoagulation With Direct Thrombin Inhibitors
6.3.4 Investigational Agents
6.3.5 Antiplatelet Agent Aspirin
6.3.6 Aspirin And Clopidogrel Combination
6.4 Anticoagulation In Special Circumstances
6.4.1 Peri-operative Anticoagulation
6.4.2 Acute Stroke
6.4.3 Anticoagulant and Antiplatelet Therapy Use in Patients With
Atrial Fibrillation Undergoing Percutaneous Coronary
Intervention
6.4.4 Non-ST Elevation Myocardial Infarction
6.4.5 Cardioversion
6.5 Non-pharmacological Methods To Prevent Strokes
6.6 Risk of Long-term Anticoagulation
6.6.1 Assessment Of Risk Of Bleeding
6.6.2 Risk Score For Bleeding
7 Management – Long-term Rate Control
7.1 Pharmacological Rate Control
7.1.1 Combination Therapy
7.2 Non-Pharmacological Rate Control
7.2.1 AV Nodal Ablation And Pacing
8 Management – Long-term Rhythm Control
8.1 Efficacy Of Antiarrhythmic Drugs In Preventing Recurrent AF
8.2 Choice Of Antiarrhythmic drugs
8.2.1 Patients With Lone AF
8.2.2 Patients With Underlying Heart Disease
8.2.2.1 Patients With Left Ventricular Hypertrophy
8.2.2.2 Patients With Coronary Artery Disease
8.2.2.3 Patients With Heart Failure
8.3 Non-Pharmacological Therapy
8.3.1 Left Atrial Catheter Ablation
8.3.2 Surgical Ablation
8.3.3 Suppression of AF Through Pacing
8.4 Upstream Therapy
8.4.1 Angiotensin-converting Enzyme Inhibitors and Angiotensin
Receptor Blockers
8.4.2 Statins
8.4.3 Polyunsaturated Fatty Acids and Aldosterone Antagonist
9 Management – Special Populations
xiv
9.1 Post-Operative AF
9.1.1 Prevention Of Post-operative AF
9.1.2 Treatment of Post-operative AF
9.2 Acute Coronary Syndrome
9.3 Wolff-Parkinson-White (WPW) Pre-excitation Syndromes
9.3.1 Sudden Death And Risk Stratification
9.4 Hyperthyroidism
9.5 Pregnancy
9.6 Hypertrophic Cardiomyopathy
9.7 Pulmonary Diseases
9.8 Heart Failure
9.9 Athletes
9.10 Valvular Heart Disease
10 Referrals
11 Audit and Evaluation
Appendixes
Glossary
References
xv
1 INTRODUCTION
1.1 DEFINITION
Atrial fibrillation (AF) is an atrial tachyarrhythmia characterized by uncoordinated

atrial activation with consequent deterioration of atrial mechanical function. The
surface ECG is characterized by ‘absolutely’ irregular RR intervals and the
absence of any distinct P waves. The P waves are replaced by fibrillary (F)
waves.
Atrial Flutter (AFl) in the typical form is characterized by a saw-tooth pattern of

regular atrial activation called flutter (F) waves on the ECG. AFl commonly
occurs with 2:1 AV block, resulting in a regular or irregular ventricular rate of 120
to 160 beats per minute (most characteristically about 150 beats per minute).
1.2 TYPES OF ATRIAL FIBRILLATION
Clinically, five types of AF are recognized based on the presentation and the
duration of the episode. These categories are set out below. (See Table 1 and
Figure 2)
<<Table 1 >>
Table 1. Classification of AF subtypes
The term ‘lone AF’ applies to young
Terminology individuals
Clinical Patternwithout
Features (under 60 years of age)
clinical or(first
Initial event echocardiographic
Symptomaticevidence of cardiopulmonary disease, May or mayincluding
not recur
hypertension.
detected episode) These Asymptomatic
patients have a favourable prognosis with respect to
Onset unknown
thromboembolism
Paroxysmal
andSpontaneous
mortality. termination <7 days and most often < Recurrent
48 hours
‘Silent AF’ being asymptomatic
Persistent is detected by an opportunistic
Not self terminating ECG or may
Recurrent
Lasting >7 days or requiring cardioversion for
present as an AF-related complication such as ischemic stroke.
termination
Long standing persistent AF that has lasted for Recurrent
This classication is useful
1 yearfor clinical
when management
it is decided of AF
to adopt a rhythm patients (Figure 1),
control
strategysymptoms are also considered.
especially when AF-related
Permanent Not terminated Established
<<Figure 1>> Terminated but relapsed
No cardioversion attempt
1.3 AF NATURAL TIME COURSE
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010
AF is a naturally
Version) (Europeanprogressive disease
heart Journal 2010;except for a small proportion of patients (2-
doi:10.1093/eurheartj/ehq278)
3%), who are free of AF-promoting conditions (see section 2.1.1, page 5), may
remain in paroxysmal AF over several decades.1 AF progresses from short rare
episodes, to longer and more frequent attacks (See Figure 2). With time, often
years, many patients will develop sustained forms of AF. Paroxysm of AF
episodes also occurs in cluster and ”AF burden” can vary markedly over months
or years.2
1
duration of the episode. These categories are set out below. (See Table 1 and
Figure 2)
<<Table 1 >>
The term ‘lone AF’ applies to young individuals (under 60 years of age) without
clinical or echocardiographic evidence of cardiopulmonary disease, including
hypertension. These patients have a favourable prognosis with respect to
thromboembolism and mortality.
‘Silent AF’ being asymptomatic is detected by an opportunistic ECG or may

1present as an AF-related complication such as ischemic stroke.
INTRODUCTION
1 INTRODUCTION
ThisDEFINITION
1.1 classication is useful for clinical management of AF patients (Figure 1),
1.1 DEFINITION
especially when AF-related symptoms are also considered.
Atrial fibrillation (AF) is an atrial tachyarrhythmia characterized by uncoordinated
Atrial fibrillation
<<Figure
atrial 1>> (AF)
activation is an atrial tachyarrhythmia
with consequent deterioration of characterized
atrial mechanicalby uncoordinated
function. The
atrial
surface activation
ECG iswith consequentby
characterized deterioration
‘absolutely’ofirregular
atrial mechanical function.
RR intervals and The
the
surface ECG
1.3 AF NATURAL
absence of any is distinct
characterized
TIME COURSE
P waves. by The
‘absolutely’
P waves irregular RR intervals
are replaced and the
by fibrillary (F)
absence
waves. of any distinct P waves. The P waves are replaced by fibrillary (F)
waves.
AF is a naturally progressive disease except for a small proportion of patients (2-
3%), who
Atrial Flutter are(AFl)
free in
of the
AF-promoting
typical formconditions (see section
is characterized 2.1.1, page
by a saw-tooth 5), may
pattern of
Atrial
remainFlutter
regular in (AFl)
paroxysmal
atrial in the
activation typical
AFcalled form is(F)
over several
flutter characterized
waves1 AF
decades. by aECG.
saw-tooth
on progresses
the pattern
from commonly
AFl of
short rare
regular
episodes,
occurs atrial
withto2:1 activation
longer called
and more
AV block, flutter
frequent
resulting (F) waves
attacksor(See
in a regular on the
Figure
irregular ECG. AFl commonly
2). With rate
ventricular time,ofoften
120
occurs
years,
to with
many
160 beats 2:1
per AV block,
patients
minute willresulting
(mostdevelop in sustained
a regular or
characteristically irregular
forms
about ventricular
of beats
150 AF. rate of
Paroxysm
per minute).of 120
AF
to 160 beats
episodes alsoper minute
occurs in (most
clustercharacteristically
and ”AF burden”about 150 beats
can vary per minute).
markedly over months
2
or years.
Clinically,
duration offive
thetypes of AF
episode. are recognized
These categories based
are seton
outthe presentation
below. and1the
(See Table and
duration
Figure 2)of the episode. These categories are set out below. (See Table 1 and
Figure 2)
<<Table 1 >>
<<Table 1 >>
The term ‘lone AF’ applies to young individuals (under 60 years of age) without
The term
clinical or‘lone AF’ applies to young
echocardiographic individuals
evidence (under 60 years
of cardiopulmonary of age)including
disease, without
clinical or echocardiographic
hypertension. These patients evidence
have a of cardiopulmonary
favourable prognosisdisease, including
with respect to
hypertension.
thromboembolism These
and patients
mortality. have a favourable prognosis with respect to
thromboembolism and mortality.
‘Silent AF’ being asymptomatic is detected by an opportunistic ECG or may
‘Silent
presentAF’ being
as an asymptomatic
AF-related is detected
complication such asby an opportunistic
ischemic stroke. ECG or may
present as an AF-related complication such as ischemic stroke.
Figure
This 1: Different types is
classication of AF. AF =for
useful atrial fibrillation;
clinical CV = cardioversion.
management of AFThe arrhythmia
patients tends to
(Figure 1),progress
This
from classication
paroxysmal
especially when is useful for
(self-terminating,
AF-related clinical,48management
usually
symptoms of AF
h) to persistent
are longer
also considered. patients (Figureor1),requiring
[non-self-terminating
cardioversion (CV)], long-standing persistent (lasting than 1 year) and eventually to permanent
especially when AF-related symptoms are also considered.
(accepted) AF. First-onset AF may be the first of recurrent attacks or already be deemed permanent.
<<Figure
Adapted from 1>>
the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart
<<Figure 1>>
AF is a naturally progressive disease except for a small proportion of patients (2-
AF
3%),is who
a naturally progressive
are free diseaseconditions
of AF-promoting except for(see
a small proportion
section 2.1.1, of patients
page (2-
5), may
3%),
remain who are free of AF-promoting
in paroxysmal AF over severalconditions
decades.(see
1
AFsection 2.1.1,from
progresses pageshort
5), may
rare
1
remain
episodes,in paroxysmal
to longer andAFmore
over frequent
several decades. AF progresses
attacks (See fromtime,
Figure 2). With shortoften
rare
episodes,
years, many to longer andwill
patients more frequent
develop attacks (See
sustained formsFigure
of AF.2).Paroxysm
With time,ofoften
AF
years, many
episodes also patients
occurs inwill develop
cluster sustained
and ”AF burden”forms of AF.
can vary Paroxysm
markedly of AF
over months
episodes
or years. also occurs in cluster and ”AF burden” can vary markedly over months
2
or years.2
Asymptomatic AF is common even in symptomatic patients, irrespective of
whether the initial presentation was persistent or paroxysmal. This has important
implications for strategies aimed at preventing AF-related complications.
<<Figure 2>> 2
Figure22: :‘Natural’
Figure ‘Natural’time
timecourse
courseof of AF.
AF. AF
AF == atrial
atrial fibrillation.
fibrillation. The dark blue boxes show aa typical
typical sequence
sequence of of
periodsininAF
periods AF against
against aa background
background of of sinus
sinus rhythm,
rhythm, and and illustrate the progression of
of AF
AF from
from silent
silent and
and
undiagnosedtotoparoxysmal
undiagnosed paroxysmal and and chronic
chronic forms,
forms, atat times
times symptomatic. The upper bars bars indicate
indicate therapeutic
therapeutic
measures that
measures that could
could be be pursued.
pursued. LightLight blue
blue boxes
boxes indicate
indicate therapies that have proven
proven effects
effects on
on ‘hard
‘hard
Asymptomatic
outcomes’ininAF,
outcomes’ AF,such
such AF asstroke
as is common
stroke or acute
or even
acute heart
heart in Red
failure.
failure. symptomatic
Red boxes indicatepatients, irrespective
therapies that
that are
are currently of
currently used
used
whether
forsymptom
for symptom the initial
relief,
relief, but may
but presentation
may in the
in futurewas
the future persistent
contribute
contribute or paroxysmal.
to reduction
to reduction This has important
of AF-related complications.
complications. Rate
Rate control
control
(greybox)
(grey box)isisvaluable
implications valuable forsymptom
for symptomaimed
for strategies relief and
relief and may
atmay improve cardiovascular
improve
preventing AF-related outcomes.
complications.
<<Figure
Journal 2010;2>>
1.4 EPIDEMIOLOGY AND PROGNOSIS
AF is the commonest sustained cardiac arrhythmia. Information on AF in

Malaysia is scarce. Hospital practice data may give a biased view of the clinical
epidemiology of AF, since only one-third of patients with AF may actually have
been admitted to hospital.
Data from predominantly western populations suggest the estimated prevalence

of AF is 0.4% to 1% in the general population. The prevalence of AF doubles with
each decade of age, from 0.5% at age 50-59 years to almost 9% at age 80-89
years.3-4
The mortality rate of patients with AF is about double that of patients in sinus
rhythm.2,5
AF is associated with a prothrombotic state, intra-atrial stasis, structural heart

disease or blood vessel abnormalities and abnormal platelets haemostasis,
leading to a predisposition to thrombus formation. This prothrombotic state leads
to stroke and thromboembolism in AF (See Table 1, Page 1). Only antithrombotic
therapy has been shown to reduce AF-related deaths.6
<<Table 2 >>
3
Stroke in AF is often severe and results in long-term disability or death.
Approximately 20% of stroke is due to AF and undiagnosed ‘silent AF’ is a likely
Table 2: Clinical events (outcomes) affected by AF
Relative change in AF
Outcome parameter patients
Asymptomatic AF is common even in symptomatic patients, irrespective of
1. Death Death
whether the initial presentation was persistent or rate doubled.
paroxysmal. This has important
implications for strategies aimed at preventing AF-related complications.
2. Stroke (includes Stroke risk increased; AF is
haemorrhagic
<<Figure 2>> stroke and associated with more severe
cerebral bleeds) stroke.
Hospitalizations are frequent in

3. EPIDEMIOLOGY
1.4 AND PROGNOSIS AF patients and may contribute
Hospitalizations
to reduced quality of life.
AF is the commonest sustained cardiac arrhythmia. Information on AF in
Malaysia is scarce. Hospital practice data may give a biased view of the clinical
epidemiology of AF, since only one-thirdWide variation,
of patients with AFfrom
may no effect
actually have
been admitted to hospital. to major reduction.
4. Quality of life and exercise
AF can cause marked distress
Data capacity
from predominantly western populations suggest the estimated prevalence
through palpitations and other
of AF is 0.4% to 1% in the general population. The prevalence of AF doubles with
AF-related
each decade of age, from 0.5% at age 50-59 years tosymptoms.
almost 9% at age 80-89
years.3-4
5. Left ventricular function Wide variation, from no change
The mortality rate of patients with AF isto
about double that of patients with
tachycardiomyopathy in sinus
rhythm.2,5
acute heart failure.
AF is associated with a prothrombotic state, intra-atrial stasis, structural heart
disease or fibrillation.
AF = atrial blood vessel abnormalities and abnormal platelets haemostasis,
leading
Outcomesto a are
predisposition to thrombus order
listed in hierarchical formation. This prothrombotic
modified state leads
from a suggestion put
to stroke in
forward and thromboembolism
a recent in AF (See 2Table
consensus document. The prevention Only
1, Page 1). of antithrombotic
these outcomes
therapy has been shown to reduce AF-related deaths.6
is the main therapeutic goal in AF patients.
<<Table 2 >>
Stroke in AF is often severe and results in long-term disability or death.

Approximately 20% of stroke is due to AF and undiagnosed ‘silent AF’ is a likely
cause of some ‘cryptogenic’ strokes.2,7 Paroxysmal AF carries the same stroke
risk as permanent or persistent AF.8
AF also account for one-third of all admissions for cardiac arrhythmias. Acute
Coronary Syndrome (ACS), aggravation of heart failure, thrombo-embolic
complications, and acute arrhythmia management are the main causes.
Quality of life and exercise capacity are degraded in patients with AF.9 This may
be related to impaired left ventricular (LV) function that accompanies the
irregular, fast ventricular rate, loss of atrial contractile function and increased
end-diastolic LV lling pressure.
4
2. PATHOPHYSIOLOGY
Understanding the pathophysiology of atrial brillation (AF) requires integration

of information from clinical, histological, electrophysiological and
echocardiographic sources. There is no single cause or mechanism that results
in AF, and it may present in a multitude of ways.
2.1 CLINICAL ASPECTS
There are many risk factors for developing AF. In the Framingham study the
development of AF was associated with increasing age, diabetes, hypertension
and valve disease. It is also commonly associated with, and complicated by HF
and strokes.
2.1.1 CAUSES AND ASSOCIATED CONDITIONS
AF is often associated with co-existing medical conditions. The underlying

conditions and factors predisposing patients to AF are listed in Table 3.
<<Table 3 >>
Table 3: Common cardiac and non-cardiac risk factors of AF.

Some of the conditions predisposing to AF may be reversible such as acute
Elevated Atrial Pressure
infections, alcohol excess, surgery, pericarditis, myocarditis, pulmonary
Systemic Hypertension
pathology and thyrotoxicosis. Therefore, long-term therapy of AF may not be
Pulmonary Hypertension
indicated once (cardiomyopathy
Myocardial disease the reversible causes
with systolic and/orhave
diastolicbeen addressed. When AF is
dysfunction)
Mitral or tricuspid valve disease
associated withvalve
Aortic or pulmonary other supraventricular arrhythmias, treatment of the primary
disease
arrhythmia reduces or eliminates the recurrence of AF.
Intracardiac tumours
Sleep apnoea
Atrial ischemia
Coronary artery disease
Approximately 30 – 40%
Inflammatory or infiltrative of cases of paroxysmal AF
atrial disease and 20 – 25% of persistent
AF occur orinpericarditis
Myocarditis young patients without demonstrable underlying disease. These
Amyloidosis
cases are often
Age-induced referred to as ‘lone AF’.
atrial fibrosis
Primary or metastatic cancer in/or adjacent to the atrial wall
Drugs
Alcohol
Caffeine
Endocrine disorders
Hyperthyroidism
Phaeochromocytoma
Changes in autonomic tone
Increased sympathetic tone
Increased parasympathetic tone
Postoperative
Cardiothoracic surgery
Oesophageal surgery
Neurogenic
Subarchnoid haemorrhage
Haemorrhagic stroke
Ischemic stroke
Idiopathic
Lone AF
Familial AF
Other
Congenital heart disease
Chronic renal disease
Obesity
5
2.1.1 CAUSES AND ASSOCIATED CONDITIONS
AF is often associated with co-existing medical conditions. The underlying

conditions and factors predisposing patients to AF are listed in Table 3.
<<Table 3 >>
Some of the conditions predisposing to AF may be reversible such as acute

infections, alcohol excess, surgery, pericarditis, myocarditis, pulmonary
pathology and thyrotoxicosis. Therefore, long-term therapy of AF may not be
indicated once the reversible causes have been addressed. When AF is
associated with other supraventricular arrhythmias, treatment of the primary
arrhythmia reduces or eliminates the recurrence of AF.
Approximately 30 – 40% of cases of paroxysmal AF and 20 – 25% of persistent

AF occur in young patients without demonstrable underlying disease. These
cases are often referred to as ‘lone AF’.
3 INITIAL MANAGEMENT
3.1 CLINICAL HISTORY, PHYSICAL EXAMINATION AND INVESTIGATIONS
The acute management of AF patients should concentrate on

Relief of symptoms
Assessment of AF-associated risk
Determination of the European Heart Rhythm Association (EHRA) score
(Table 5, page 7)
Estimation of stroke risk (see Section 6.1, page 26)
Search for conditions that predispose to AF (see Section 2.1.1, page 5) and
Search for complications of the arrhythmia (see Section 1.4, page 3)
With the above in mind, a thorough medical history should be obtained from the
patient with suspected or known AF (see Table 4).
Table 4:
4: Relevant
Relevant questions
Table
<<Table 4>> questions toto be
be put
put to
to a
a patient
patient with
with suspected
suspected or
or known
known AF
AF
Does the heart rhythm during the episode feel regular or irregular?
The EHRA any

Is there symptom score (seefactor
precipitating Tablesuch
5) provides a simpleemotion,
as exercise, clinical tool
or for
assessing symptoms during AF. The score only considers symptoms that are
alcohol intake?
attributable to AF and reverse or reduce upon restoration of sinus rhythm or with
effective rate control.
Are symptoms during the episodes moderate or severe—the severity
may be5 expressed
<<Table >> using the EHRA score,3 which is similar to the
CCS-SAF score.41
Are the episodes frequent or infrequent, and are they long or short
3.1.1 DETECTION
lasting?
Those with undiagnosed AF can receive treatment sooner if an opportunistic
Is there a history of concomitant disease such as hypertension,
case finding is undertaken. Routine palpation of the radial pulse (not less than 20
coronaryduring
seconds) heartscreening
disease, heart pressure
of blood failure, will
peripheral vascular
be a good disease,
opportunity to pick up
cerebrovascular
undiagnosed disease, stroke, diabetes, or chronic pulmonary
atrial fibrillation.
disease?
In patients presenting with any of the following:
breathlessness/dyspnoea,
Is xthere an alcohol abuse habit?
x palpitations,
syncope/dizziness,
Is xthere a family history of AF?
x chest discomfort or stroke/TIA,
manual
AF
AF == atrial pulse palpation
atrial fibrillation;
fibrillation; CCS-SAF
CCS-SAF ==should
Canadianbe
Canadian performedSociety
Cardiovascular
Cardiovascular to assess
Society Severity for
Severity in
in theFibrillation;
Atrial
Atrial presence
Fibrillation; of== an
EHRA
EHRA
irregular
European Heart
European pulse
Heart thatAssociation.
Rhythm
Rhythm may indicate AF.
Association.
6
patient with suspected or known AF (see Table 4).
<<Table 4>>
3 INITIAL MANAGEMENT
The EHRA symptom score (see Table 5) provides a simple clinical tool for
3.1 CLINICAL HISTORY, PHYSICAL EXAMINATION AND INVESTIGATIONS
assessing symptoms during AF. The score only considers symptoms that are
The acute management of AF patients should concentrate on
effective rate control.
Relief of symptoms
Assessment of AF-associated risk
<<Table 5 >>
Determination of the European Heart Rhythm Association (EHRA) score
Table 5 : EHRA score of AF-related symptoms
(Table 5, page 7)
Estimation of stroke risk (see Section 6.1, page 26)
Search for conditions of
Classification that predisposesymptoms
AF-related to AF (see Section
(EHRA2.1.1, page 5) and
score)
3.1.1 DETECTION
Search for complications of the arrhythmia (see Section 1.4, page 3)
EHRAwithclass Explanation
Those undiagnosed AF can receive treatment sooner if an opportunistic
patient
EHRA with
I suspected
‘No or known AF (see Table 4).
symptoms’
seconds) during screening of blood pressure will be a good opportunity to pick up
undiagnosed atrial fibrillation.
<<Table
EHRA 4>>II ‘Mild symptoms’; normal daily activity not affected
EHRA III
x breathlessness/dyspnoea,‘Severe symptoms’; normal daily activity affected
Thex EHRA palpitations,
symptom score (see Table 5) provides a simple clinical tool for
EHRA
assessing IVsymptoms‘Disabling
x syncope/dizziness, symptoms’; normal daily activity
during AF. The score only considers symptoms that are
x chest discontinued
discomfort or stroke/TIA,
manual
effectivepulse palpation should be performed to assess for the presence of an
rate control.
irregular pulse that may indicate AF.
AF = atrial fibrillation; EHRA = European Heart Rhythm Association.
<<Table 5 >>
3.1.1 DETECTION
Those with undiagnosed AF can receive treatment sooner if an opportunistic

seconds) during screening of blood pressure will be a good opportunity to pick up
undiagnosed atrial fibrillation.

x breathlessness/dyspnoea,
x palpitations,
x syncope/dizziness,
x chest discomfort or stroke/TIA,
manual pulse palpation should be performed to assess for the presence of an
irregular pulse that may indicate AF.
3.1.1.1 ELECTROCARDIOGRAM
The diagnosis of AF requires confirmation by ECG, sometimes in the form

of bedside telemetry, ambulatory Holter recordings and event loop
recordings. 2, 10
If AF is present at the time of recording, a standard 12-lead ECG is sufficient to

confirm the diagnosis. In paroxysmal AF, 7-days Holter ECG recording or daily
and symptom-activated event recordings may document the arrhythmia in 70% of
AF patients.2
The search for AF should be intensified;

7 including prolonged monitoring, when
patients
of bedside telemetry, ambulatory Holter recordings and event loop
recordings. 2, 10
If AF is present at the time of recording, a standard 12-lead ECG is sufficient to

confirm the diagnosis. In paroxysmal AF, 7-days Holter ECG recording or daily
and symptom-activated event recordings may document the arrhythmia in 70% of
AF patients.2
The search for AF should be intensified; including prolonged monitoring, when

patients
Are highly symptomatic (EHRA III & IV)
Present with recurrent syncope and
After a cryptogenic stroke.11, 12
In stroke survivors, a step-wise addition of ve daily short-term ECGs, one 24 h

Holter ECG, and another 7-day Holter ECG will each increase the detection rate
of AF by a similar extent.11
3.2 DIAGNOSTIC EVALUATION
The initial diagnostic work-up is driven by the initial presentation.
The time of onset of AF should be established to dene the type of AF (Figure 2).
Patients with AF and signs of acute heart failure require urgent rate control and
often cardioversion. An urgent transthoracic echocardiogram (TTE) should be
performed in haemodynamically-compromised patients to assess LV and valvular
function and right ventricular pressure. If AF duration is >48 h or there is doubt
about its duration, transesophageal echocardiogram (TOE) should be used to
rule out intracardiac thrombus prior to cardioversion.13
Patients with stroke or TIA require immediate stroke diagnosis, usually via
emergency computed tomography (CT).
Patients should be assessed for risk of stroke. Most patients with acute AF will
require anticoagulation unless they are at low risk of thromboembolic
complications (no stroke risk factors) and no cardioversion is necessary (e.g. AF
terminates within 24 – 48 h).
After the initial management of symptoms and complications, underlying causes

of AF should be sought. A TTE is useful to detect ventricular, valvular, and atrial
disease as well as rare congenital heart disease. Thyroid function tests, a full
blood count, a serum creatinine measurement and analysis for proteinuria,
measurement of blood pressure, and a test for diabetes mellitus are useful. A
serum test for hepatic function may be considered in selected patients. A stress
test is reasonable in patients with signs or risk factors for coronary artery
disease. Patients with persistent signs of LV dysfunction and/or signs of
myocardial ischemia are candidates for coronary angiography
Table 6 lists the clinical evaluation that may be necessary in patients with AF.
<<Table 6 >>
3.3 ECHOCARDIOGRAPHY
TTE should be performed in patients with AF:

o For whom a baseline echocardiogram is important for long-term
management.
o For whom a rhythm-control strategy that includes cardioversion
(electrical or pharmacological) is being considered.
o In whom there is a high risk or a suspicion of underlying
structural/functional heart disease
8 (such as heart failure or heart
murmur) that influences their subsequent management (for
Table 6 : Clinical Evaluation in Patients With AF
Minimum evaluation
1. Electrocardiogram, to identify
Rhythm (verify AF)
LV hypertrophy
P-wave duration and morphology or fibrillatory waves
Preexcitation
Bundle-branch block
Prior MI
Other atrial arrhythmias
To measure and follow the R-R, QRS, and QT intervals in conjunction with
antiarrhythmic drug therapy
2. Transthoracic echocardiogram, to identify
Valvular heart disease
LA and RA size
LV size and function
Peak RV pressure (pulmonary hypertension)
LV hypertrophy
LA thrombus (low sensitivity)
Pericardial disease
3. Blood tests of thyroid, renal, and hepatic function
For a first episode of AF, when the ventricular rate is difficult to control
Additional testing
One or several tests may be necessary.
1. Six-minute walk test
If the adequacy of rate control is in question
2. Exercise testing
If the adequacy of rate control is in question (permanent AF)
To reproduce exercise-induced AF
To exclude ischemia before treatment of selected patients with a type IC
antiarrhythmic drug
3. Holter monitoring or event recording
If diagnosis of the type of arrhythmia is in question
As a means of evaluating rate control
4. Transesophageal echocardiography
To identify LA thrombus (in the LA appendage)
To guide cardioversion
5. Electrophysiological study
To clarify the mechanism of wide-QRS-complex tachycardia
To identify a predisposing arrhythmia such as atrial flutter or paroxysmal
supraventricular tachycardia
To seek sites for curative ablation or AV conduction block/modification
6. Chest radiograph, to evaluate
Lung parenchyma, when clinical findings suggest an abnormality
Pulmonary vasculature, when clinical findings suggest an abnormality
Type IC refers to the Vaughan Williams classification of antiarrhythmic drugs (see Appendix D). AF = atrial
fibrillation; AV = atrioventricular; LA = left atrial; LV = left ventricular; MI = myocardial infarction; RA = right
atrial; RV = right ventricular.
9
disease. Patients with persistent signs of LV dysfunction and/or signs of
myocardial ischemia are candidates for coronary angiography
Table 6 lists the clinical evaluation that may be necessary in patients with AF.
<<Table 6 >>
3.3 ECHOCARDIOGRAPHY
TTE should be performed in patients with AF:

o For whom a baseline echocardiogram is important for long-term
management.
o For whom a rhythm-control strategy that includes cardioversion
(electrical or pharmacological) is being considered.
o In whom there is a high risk or a suspicion of underlying
structural/functional heart disease (such as heart failure or heart
murmur) that influences their subsequent management (for
example, choice of antiarrhythmic drug)
o In whom refinement of clinical risk stratification for antithrombotic
therapy is needed.
In patients with AF who require anticoagulation therapy based on relevant clinical

criteria, TTE need not be routinely performed.
TOE should be performed in patients with AF:

o Where TTE is technically difficult and/or of questionable quality and
where there is a need to exclude cardiac abnormalities
o For whom TOE-guided cardioversion is being considered. (See
section 6.4.5, page 38)
3.4 CLINICAL FOLLOW-UP
The specialist caring for the AF patient should not only perform the baseline
assessment and institute the appropriate treatment, but also suggest a structured
plan for follow-up.
Important considerations during follow-up of the AF patient are listed below:
x Has the risk prole changed (e.g. new diabetes or hypertension), especially
with regard to the indication for anticoagulation?
x Is anticoagulation now necessary—have new risk factors developed, or
has the need for anticoagulation passed, e.g. postcardioversion in a
patient with low thrombo-embolic risk?
x Have the patient’s symptoms improved on therapy; if not, should other

therapy be considered?
x Are there signs of proarrhythmia or risk of proarrhythmia; if so, should the

dose of an antiarrhythmic drug be reduced or a change made to another
therapy?
x Has paroxysmal AF progressed to a persistent/permanent form, in spite of

antiarrhythmic drugs; in such a case, should another therapy be
considered?
x Is the rate control approach working properly; has the target for heart rate
at rest and during exercise been reached?
The diagnosis of AF requires documentation by ECG.2,10

10
In patients with suspected AF, an attempt to record an ECG should be made
dose of an antiarrhythmic drug be reduced or a change made to another
therapy?
x Has paroxysmal AF progressed to a persistent/permanent form, in spite of

antiarrhythmic drugs; in such a case, should another therapy be
considered?
x Is the rate control approach working properly; has the target for heart rate
Keypoints at rest and during exercise been reached?
I BIB The diagnosis of AF requires documentation by ECG.2,10
I BIB In patients with suspected AF, an attempt to record an ECG should be made
when symptoms suggestive of AF occur.2,14
A simple symptom score (EHRA class) is recommended to quantify AF-related

I BIB
symptoms.2,15
All patients with AF should undergo a thorough physical examination, and a

I CIC cardiac- and arrhythmia-related history should be taken.
I BIB In patients with severe symptoms, documented or suspected heart disease, or

risk factors, an echocardiogram is recommended.2,16,17
In patients treated with antiarrhythmic drugs, a 12-lead ECG should be recorded

I CIC at regular intervals during follow-up.
IIaB In patients with suspected symptomatic AF, additional ECG monitoring should be
IIa B considered in order to document the arrhythmia.2,18
IIaB Additional ECG monitoring should be considered for detection of ‘silent’ AF in

IIa B
patients who may have sustained an AF-related complication. 2,19
In patients with AF treated with rate control, Holter ECG monitoring should be
IIaC
IIa C considered for assessment of rate control or bradycardia.
IIa C
IIaC In young active patients with AF treated with rate control, exercise testing should
be considered in order to assess ventricular rate control.
In patients with documented or suspected AF, an echocardiogram should be

IIaC
IIa C considered.
IIaC Patients with symptomatic AF or AF-related complications should be considered

IIa C for referral to a cardiologist.
IIaC A structured follow-up plan prepared by a specialist is useful for follow-up by a

IIa C general or primary care physician.
IIbB In patients treated with rhythm control, repeated ECG monitoring may be
IIb B
considered to assess the efficacy of treatment.2,20,21
IIbC Most patients with AF may benet from specialist follow-up at regular intervals.
IIb C
<<Figure 3>>
11
12
Figure 3: Choice of rate and rhythm control strategies. Rate control is needed for most patients with AF unless the heart rate during AF is naturally slow. Rhythm
control may be added to rate control if the patient is symptomatic despite adequate rate control, or if a rhythm control strategy is selected because of factors such
as the degree of symptoms, younger age, or higher activity levels. Permanent AF is managed by rate control unless it is deemed possible to restore sinus rhythm
when the AF category is re-designated as ‘long-standing persistent’. Paroxysmal AF is more often managed with a rhythm control strategy, especially if it is
symptomatic and there is little or no associated underlying heart disease. Solid lines indicate the first-line management strategy. Dashed lines represent fall-back
objectives and dotted lines indicate alternative approaches which may be used in selected patients.
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal 2010; doi:10.1093/eurheartj/ehq278)
4. MANAGEMENT PRINCIPLES
4.1 GENERAL PRINCIPLES
In patients with AF or AFI, the aims of treatment involve the following five
objectives.
I Relief of symptoms, such as palpitations, dizziness, fatigue and dyspnoea,

is paramount to the patient.
II. The prevention of serious complications, such as thromboembolism

(particularly ischaemic stroke) and heart failure, is equally important.
III. Optimal management of concomitant cardiovascular disease.
IV. Rate control.
V. Correction of rhythm disturbance.
These goals are not mutually exclusive and may be pursued simultaneously. The
initial strategy may differ from the long-term therapeutic goal.
A fundamental question to be answered for every patient with AF or AFI is

whether to obtain and maintain sinus rhythm by pharmacological or
nonpharmacological means (a rhythm-control strategy), or whether to aim
primarily to control heart rate rather than the rhythm (a rate-control strategy).
For patients with symptomatic AF lasting many weeks, initial therapy may be
anticoagulation and rate control while the long-term goal is to restore sinus
rhythm.
If rate control offers inadequate symptomatic relief, restoration of sinus rhythm

becomes a clear long-term goal. When cardioversion is contemplated and the
duration of AF is unknown or exceeds 48 h, anticoagulation will be necessary.
Early cardioversion may be necessary if AF causes hypotension or worsening

heart failure. In contrast, amelioration of symptoms by rate control in older
patients may steer the clinician away from attempts to restore sinus rhythm. In
some circumstances, when the initiating pathophysiology of AF is reversible, as
for instance in the setting of thyrotoxicosis or after cardiac surgery, no long-term
therapy may be necessary.
Regardless of the approach, the need for anticoagulation is based on stroke risk
and not on whether sinus rhythm is maintained.
For rate and rhythm control, drugs remain the first choice. Radiofrequency
ablation may be considered in symptomatic AF and in lone AF to avoid long-term
drug therapy. In selected individuals undergoing cardiac surgery, surgical maze
procedure may be a therapeutic option.
4.2 THROMBOEMBOLIC PROPHYLAXIS
Antithrombotic therapy must be considered in all patients with AF. Strategies that
may reduce thromboembolic risk include the following treatments:
13
• Anticoagulants such as Vitamin K Antagonist,
For rate and rhythm control, drugs remain the first choice. Radiofrequency
ablation may be considered in symptomatic AF and in lone AF to avoid long-term
drug therapy. In selected individuals undergoing cardiac surgery, surgical maze
procedure may be a therapeutic option.
4.2 THROMBOEMBOLIC PROPHYLAXIS
Antithrombotic therapy must be considered in all patients with AF. Strategies that
may reduce thromboembolic risk include the following treatments:
• Anticoagulants such as Vitamin K Antagonist,

• Antiplatelet agents, such as aspirin and clopidogrel
• Intravenous (IV) heparin or low molecular weight heparin (LMWH)
• Left atrial appendage (LAA) occlusion, either surgically or percutaneously.
The decision regarding the method of reduction in the risk of stroke, should take
into account both the person’s risk of thromboembolism and their risk of bleeding.
It is important to remember that vitamin K antagonist such as Warfarin is very
effective and reduces the risk of stroke overall by two thirds. (For details see
Section 6, page 26)
4.3. HEART RATE CONTROL VERSUS RHYTHM CONTROL
Rate control involves the use of chronotropic drugs or electrophysiological or

surgical interventions to reduce the rapid heart rate (ventricular rate) often found
in patients with AF. Although the atria continue to fibrillate with this strategy, it is
nonetheless thought to be an effective treatment as it improves symptoms and
reduces the risk of associated morbidity. However, the persistence of the
arrhythmia continues the risk of stroke and thromboembolic events occurring.
Administering antithrombotic drugs reduces this risk. (See Figure 3, page 12)
Rhythm control involves the use of electrical or pharmacological cardioversion or

electrophysiological or surgical interventions to convert the arrhythmia associated
with AF to normal sinus rhythm. Patients who have been successfully
cardioverted are generally administered antiarrhythmic drugs for the long term to
help prevent the recurrence of AF. The rhythm control strategies also require the
appropriate administration of antithrombotic therapy to reduce the risk of stroke
and thromboembolic events occurring.
Randomized trials comparing outcomes of rhythm versus rate control strategies

in patients with AF are summarized in Table 7 and 8.22-28
<<Table 7>>
<<Table 8>>
14
Table 7: General characteristic s of rhythm control and rate control trials in patients with AF
Trial Ref Patients Mean Mean Inclusion criteria Primary outcome parameter Patients reaching primary
(n) age follow-up outcome (n)
(years) (years) Rate Rhythm P
control control
Persistent AF 76/125 70/127
PIAF (2000) 22 252 61.0 1.0 Symptomatic improvement 0.32
(7–360 days) (60.8%) (55.1%)
Paroxysmal AF or
persistent AF, age >65 310/2027 356/2033
AFFIRM (2002) 23 4060 69.7 3.5 All-cause mortality 0.08
years, or risk of stroke or (25.9%) (26.7%)
death
Composite: cardiovascular
Persistent AF or flutter for
death, CHF, severe bleeding,
<1 years and 1–2
pacemaker implantation, 44/256 60/266
RACE (2002) 24 522 68.0 2.3 cardioversions over 2 0.11
thrombo-embolic events, (17.2%) (22.6%)
years and oral
severe adverse effects of
anticoagulation
antiarrhythmic drugs
Persistent AF
Composite: overall
(>4 weeks and
mortality, cerebrovascular 10/100 9/100
STAF (2003) 25 200 66.0 1.6 <2 years), LA size 0.99
complications, CPR, embolic (10.0%) (9.0%)
>45 mm, CHF NYHA
15
events
II–IV, LVEF <45%
First clinically overt Composite: death,
persistent AF (>–7 days thrombo-embolic events; 1/101 4/104
HOTCAFE (2004) 26 205 60.8 1.7 > 0.71
and <2 years), intracranial/major (1.0%) (3.9%)
age 50–75 years haemorrhage
LVEF <–35%, symptoms
of CHF, history of AF 175/1376 182/1376
AF-CHF (2008) 27 1376 66 3.1 Cardiovascular death 0.59
(>–6 h or (25%) (27%)
DCC <last 6 months)
Composite of total
mortality, symptomatic
cerebral infarction,
89/405 64/418
J-RHYTHM (2009) 28 823 64.7 1.6 Paroxysmal AF systemic embolism, major 0.012
(22.0%) (15.3%)
bleeding, hospitalization for
heart failure, or physical/
psychological disability
AF = atrial fibrillation; AFFIRM = Atrial Fibrillation Follow-up Investigation of Rhythm Management; CHF = congestive heart failure; CPR = cardiopulmonary
resuscitation; DCC = direct current cardioversion; HOT CAFE´ = How to Treat Chronic Atrial Fibrillation; J-RHYTHM = Japanese Rhythm Management Trial for
Atrial Fibrillation; LVEF = left ventricular ejection fraction; NYHA = New York Heart Association; PIAF = Pharmacological Intervention in Atrial Fibrillation; RACE =
RAte Control versus Electrical cardioversion for persistent atrial fibrillation; STAF = Strategies of Treatment of Atrial Fibrillation.
Table 8: Comparison of adverse outcomes in rhythm control and rate control trials in patients with AF
Trial Ref Death from all causes Deaths from Deaths from non- Stroke Thrombo-embolic Bleeding
(in rate/rhythm) cardiovascular cardiovascular causes events
causes
a
PIAF (2000) 22 4 1/1 1 ND ND ND
AFFIRM (2002) 23 666 (310/356) 167/164 113/165 77/80 ND 107/96
RACE (2002) 24 36 18/18 ND ND 14/21 12/9
16
STAF (2003) 25 12 (8/4) 8/3 0/1 1/5 ND 8/1
HOT CAFÉ (2004) 26 4 (1/3) 0/2 1/1 0/3 ND 5/8
AF-CHF (2008) 27 228/217 175/182 53/35 11/9 ND ND
a
Total number of patients not reported.
AF = atrial fibrillation; AFFIRM = Atrial Fibrillation Follow-up Investigation of Rhythm Management; HOT CAFE´ = HOw to Treat Chronic Atrial Fibrillation; ND = not
determined; PIAF = Pharmacological Intervention in Atrial Fibrillation; RACE = RAte Control versus Electrical cardioversion for persistent atrial fibrillation; STAF =
Strategies of Treatment of Atrial Fibrillation.
The consistent nding in all ve studies was that rhythm control offered no
survival advantage and, in most cases, had little effect on morbidity and quality of
life. However, it should be emphasised that these conclusions are not necessarily
applicable to all groups of patients. The ve recent studies enrolled mostly older
patients with additional risk factors for stroke, many of whom also had heart
failure. Younger patients with normal hearts and primarily paroxysmal atrial
brillation (PAF) were not well represented. Importantly, in a predened subgroup
of AFFIRM participants aged less than 65 years, hazard ratios for death showed
a paradoxical trend towards superiority of the rhythm-control strategy.
The initial therapy after onset of AF should always include adequate

antithrombotic treatment and control of the ventricular rate. If the ultimate goal is
restoration and maintenance of sinus rhythm, rate control medication should be
continued throughout follow-up, unless continuous sinus rhythm is present. The
goal is to control the ventricular rate adequately whenever recurrent AF occurs.
The decision to add rhythm control therapy to the management of AF requires an

individual decision and should therefore be discussed at the beginning of AF
management. Before choosing rate control alone as a long-term strategy, the
clinician should consider how permanent AF is likely to affect the individual
patient in the future and how successful rhythm control is expected to be (Figure
3, page 12). Symptoms related to AF are an important determinant in making the
decision to opt for rate or rhythm control (e.g. globally assessed by the EHRA
score, Table 5, page 7), in addition to factors that may inuence the success of
rhythm control. The latter include a long history of AF, older age, more severe
associated cardiovascular diseases, other associated medical conditions, and
enlarged LA size.
A rate-control strategy should be the preferred initial option in the following

patients with persistent AF:
x Over 65 years old
x With coronary artery disease and/or left ventricular dysfunction
x With contraindications to antiarrhythmic drugs
x Unsuitable for cardioversion*
A rhythm-control strategy should be the preferred initial option in the following

patients with persistent AF:
x Those who are symptomatic
x Younger patients
x Those presenting for the first time with lone AF
x Those with AF secondary to a treated/corrected precipitant
Keypoints
Rate control should be the initial approach in elderly patients with AF and minor
IA
IA symptoms (EHRA class 1).23,24,27
Rhythm control is recommended in patients with symptomatic (EHRA class 2)

IBIB
AF despite adequate rate control.2,21,29,30,31
Rate control should be continued throughout a rhythm control approach to

IA
IA ensure adequate control of the ventricular rate during recurrences of AF. 23
Rhythm control as an initial approach should be considered in young

IIaC
IIaC symptomatic patients in whom catheter ablation treatment has not been ruled
out.
17 in patients with AF secondary to a trigger
Rhythm control should be considered
IIaC
or substrate that has been corrected (e.g. ischaemia, hyperthyroidism).
AF despite adequate rate control.
Rate control should be continued throughout a rhythm control approach to

IA ensure adequate control of the ventricular rate during recurrences of AF. 23
Rhythm control as an initial approach should be considered in young

IIaC symptomatic patients in whom catheter ablation treatment has not been ruled
out.
Rhythm control should be considered in patients with AF secondary to a trigger

IIac
IIaC or substrate that has been corrected (e.g. ischaemia, hyperthyroidism).
IIaB Rhythm control in patients with AF and AF-related heart failure should be
IIaB
considered for improvement of symptoms.29,30,32
5. MANAGEMENT – ACUTE-ONSET AF
5. MANAGEMENT – ACUTE-ONSET AF
5.1 ACUTE AF IN HEMODYNAMICALLY UNSTABLE PATIENTS
5.1 ACUTE AF IN HEMODYNAMICALLY UNSTABLE PATIENTS
The majority of patients who present with AF are hemodynamically stable but
there is a small group of
The majority of patients whopresent
patients who are significantly
with AF are compromised by the
hemodynamically onset
stable but
of AF. These
therepatients
is a smallrequire
group ofimmediate hospitalization
patients who are significantlyand urgent intervention
compromised by the onset
to preventoffurther deterioration.
AF. These patients require immediate hospitalization and urgent intervention
to prevent further deterioration.
Those considered in this group are; 33
Those considered in this group are; 33
x Those with a ventricular rate greater than 150 bpm
x x Those
With ongoing with pains,
chest a ventricular
or rate greater than 150 bpm
x With ongoing chest pains, or
Criticalxperfusion.
x Critical perfusion.
In these circumstances, the concerns regarding intervention in the absence of
In these circumstances, the concerns regarding intervention in the absence of
anticoagulation and echocardiography are counterbalanced by the need for
anticoagulation and echocardiography are counterbalanced by the need for
urgent treatment.
urgent treatment.
5.1.1 ACUTE
5.1.1RATE CONTROL
ACUTE RATE CONTROL
It is important to understand
It is important that inthat
to understand these circumstances
in these circumstances the the
slow
slow onset
onsetofof
digoxin makes
digoxinit makes
inappropriate for useforinuse
it inappropriate thisin situation. Patients
this situation. whose
Patients whoseAFAFisis
associatedassociated
with thyrotoxicosis will not
with thyrotoxicosis will respond
not respond to any
to anymeasures
measuresuntil untilthe
the
underlyingunderlying
thyroid disease is first treated.
thyroid disease Patients
is first treated. with with
Patients accessory
accessorypathway
pathway such
such
as the Wolff-Parkinson-White (WPW)(WPW)
as the Wolff-Parkinson-White syndrome are particularly
syndrome at risk
are particularly following
at risk following
the onset theof onset
AF because they can
of AF because theypresent
can present with with
very very
rapid ventricular
rapid ventricularrates
rates
(greater
(greater than 200 than
bpm)200and bpm)
may and mayspecific
need need specific management.
management.
Whenpresent
When patients patients with
present with unacceptably
unacceptably high ventricular
high ventricular raterate
the the primary
primary aimisis
aim
one of rateone of rate control.
control.
AF with
AF with slow slow ventricular
ventricular rates mayrates may respond
respond to atropine
to atropine (0.5 (0.5
– 2 –mg
2 mg i.v.),
i.v.), butbut many
many
patients with symptomatic bradyarrhythmia may require either urgent placement
patients with symptomatic bradyarrhythmia may require either urgent placement
of a temporary pacemaker lead in the right ventricle and/or cardioversion.
of a temporary pacemaker lead in the right ventricle and/or cardioversion.
Acute initiation of rate control therapy should usually be followed by a long-term
Acute initiation of rate
rate control controldetails
strategy; therapy should
of drugs and usually
doses arebegiven
followed by a7 on
in Section long-term
page 66.
rate control strategy; details of drugs and doses are given in Section 7 on page 66.
Keypoints
In the acute setting in the absence of pre-excitation, i.v. administration of ȕ-
IA acute
In the settingorinnon-dihydropyridine
blockers the absence of pre-excitation,
calcium channeli.v. administration
antagonists of ȕ-
is recommended to
blockers orslow the ventricular response
non-dihydropyridine calciumto AF, exercising
channel caution in is
antagonists patients with
recommended to
34
slow the ventricular
hypotension response to AF, exercising caution in patients with
or heart failure.
In the acute setting, i.v. administration of amiodarone is recommended to control

IBIB
the heart rate in patients with AF and concomitant heart failure, or in the setting
of hypotension.35
IC In pre-excitation, preferred drugs 18

are class I antiarrhythmic drugs (See Appendix
D) or amiodarone.
hypotension or heart failure.34
In the acute setting, i.v. administration of amiodarone is recommended to control

IB
the heart rate in patients with AF and concomitant heart failure, or in the setting
of hypotension.35
ICIC In pre-excitation, preferred drugs are class I antiarrhythmic drugs (See Appendix
D) or amiodarone.
When pre-excited AF is present, ß-blockers, non-dihydropyridine calcium

IIIC
IIIC channel antagonists, digoxin, and adenosine are contraindicated.
<<Table 9>>
5.1.2 PHARMACOLOGICAL CARDIOVERSION

Table 9 : Intravenous pharmacological agents for acute control of ventricular rate in AF/AFL
Drug In the presence

Commonly of other
Onsetcardiac
of abnormalities (e.g.
Commonly-used Adversehypertensive
Limitationsheart disease,
Commonly-
valvular
usedheart
loadingdisease),
dose (IV)
onset of maintenance
action AF with acceptable
dose (IV)
effects ventricular ratesusedmayoralstill
maintenance
compromised cardiac function. While rate control is unlikely to bring about clinical
dose for long-
improvement in these circumstances, there is a need for the restorationcontrol of sinus
term rate
Beta-blockers rhythm.
Esmolol 0.5 mg/kg 5 min 0.05 to 0.2 mg/ Hypotension, Negative Oral
(very short- over 1 min
acting) Pharmacological cardioversion ofkg/min
AF infusion heart block,
may be initiated inotropic
bradycardia,by a bolus effect
preparation
administration
not available
of an antiarrhythmic drug. Although the conversion
asthma, rate
heart with antiarrhythmic drugs
failure
is lower than with direct current cardioversion (DCCV), it does not require
Metoprolol conscious sedation or anesthesia, and may facilitate the choice In peopleof antiarrhythmic
23.75 to 200
with heart mg/day
drug therapy to prevent recurrent AF. failure, lower (divided doses)
doses may
be advisable.
Most patients who undergo pharmacological cardioversionNegativerequire continuous
medical supervision and ECG monitoring during the druginotropicinfusion and for a
effect
Propanolol 0.15mg/kg over 5 5 min N/A 80 to 240
period afterwards
min (usually about half the drug elimination half-life)mg/day
to (divided
detect
proarrhythmic events such as ventricular proarrhythmia, sinus node arrest, doses) or
atrioventricular block.
Several
Calcium channel blockers agents are available for pharmacological cardioversion (see Table 10 on
Diltiazem Hypotension, In people 120 to 360
page 20). heart block, with heart mg/day
heart failure
failure, lower (once daily
doses may long-
<<Table 10>> be advisable. acting)
Negative
inotropic
In clinical
Verapamil
practice, 3 amiodarone
0.075 to 0.15
mg/kg over 2 min
to 5 min
isN/Athe most common agent
used in the
120 to 360 mg/
effect
day (divided
management of patients presenting in AF with haemodynamic compromise, as it
doses or once
daily long-
appears to have a hybrid 34 effect of rapid reduction in ventricular rate acting)most
in
hypotension
Other
or heart
patients with failure.
a proportion of these reverting to sinus rhythm over a longer period.
Digoxin 0.25 to 1.0 2 hr 0.125 to 0.25 Digoxin N/A 0.0625 to 0.375
mg
In the acute setting,
<<Figure 4>>i.v. administration of mg/day toxicity, heart
amiodarone is recommended to mg/day
control
IB block, (individualise
the heart rate in patients with AF and concomitant heart bradycardia
failure, or in thedosage)
setting
35
of hypotension.
Amiodarone 5 mg/kg Variable 50 mg/hour Hypotension, N/A 100 to 200
over 20 min (10 min to infusion back pain, mg/day
4 hours) heart block,
IC In pre-excitation, preferred drugs are class I antiarrhythmic
phlebitis drugs (See Appendix
D) or amiodarone.
Note: Administration of beta-blockers together with IV verapamil is contraindicated.
When pre-excited AF is present, ß-blockers, non-dihydropyridine calcium
N/A = not available
IIIC Adapted from: Fuster V, Ryden LE, Asinger RW, et al.134
channel antagonists, digoxin, and adenosine are contraindicated.
<<Table 9>>
In the presence of other cardiac abnormalities (e.g. hypertensive heart disease,

valvular heart disease), onset of AF with acceptable ventricular rates may still
improvement in these circumstances, there is a need for the restoration of sinus
rhythm.
Pharmacological cardioversion of AF may be initiated by a bolus administration

of an antiarrhythmic drug. Although the 19
conversion rate with antiarrhythmic drugs
is lower than with direct current cardioversion (DCCV), it does not require
In the presence of other cardiac abnormalities (e.g. hypertensive heart disease,

valvular heart disease), onset of AF with acceptable ventricular rates may still
improvement in these circumstances, there is a need for the restoration of sinus
rhythm.
hypotension or heart
Pharmacological failure.34 of AF may be initiated by a bolus administration
cardioversion
of an antiarrhythmic drug. Although the conversion rate with antiarrhythmic drugs
In
is the acute
lower setting,
than with i.v. administration
direct of amiodarone
current cardioversion is recommended
(DCCV), it does not to control
require
the heart rate
conscious in patients
sedation with AF and
or anesthesia, andconcomitant heart
may facilitate failure, of
the choice or antiarrhythmic
in the setting
35
of hypotension.
drug therapy to prevent recurrent AF.
In pre-excitation,
Most patients whopreferred
undergodrugs are class I antiarrhythmic
pharmacological drugs
cardioversion (Seecontinuous
require Appendix
D) or amiodarone.
medical supervision and ECG monitoring during the drug infusion and for a
period afterwards (usually about half the drug elimination half-life) to detect
When pre-excited
proarrhythmic eventsAFsuch
is as
present, ß-blockers,
ventricular non-dihydropyridine
proarrhythmia, calcium
sinus node arrest, or
channel antagonists,
atrioventricular block.digoxin, and adenosine are contraindicated.
Several agents
<<Table 9>> are available for pharmacological cardioversion (see Table 10 on
page 20).
<<Table 10>>
In the
Table 10: presence of for
Drug and doses other cardiac abnormalities
pharmacological (e.g. hypertensive
conversion of (recent-onset) AF heart disease,
In clinical
valvular practice,
heart disease), amiodarone
onset of AF is with
the acceptable
most common agentrates
ventricular usedmay in still
the
managementDrug of
compromised patients
cardiac presenting
function.
Dose WhileinrateAF control
withdose
Follow-up haemodynamic compromise,
is unlikely to bring as it
Riskabout clinical
appears
improvement
Amiodaroneto have a 5hybrid
in these i.veffect
over 1h of 50mg/kg
circumstances,
mg/kg rapid
there reduction in
for ventricular
is a needPhlebitis,
thehypotension.rate
restoration in
Willof most
sinus
slow
patients with a proportion of these reverting to sinus rhythm
rhythm. over rate.
the ventricular a longer
Delayedperiod.
AF
conversion to sinus rhythm.
Flecainide 200-300 mg p.o N/A Not suitable for patients with
<<Figure 4>> cardioversion of AF may be initiatedmarked
Pharmacological by astructural
bolus administration
heart disease,
of an antiarrhythmic drug. Although the conversion rate
maywith antiarrhythmic
prolong QRS duration, anddrugs
hence theitQTdoes
is lower than with direct current cardioversion (DCCV), interval;not
and may
require
inadvertently increase the
conscious sedation or anesthesia, and may facilitate the choice
ventricular rateof antiarrhythmic
due to conversion
drug therapy to prevent recurrent AF. to atrial flutter and 1:1 conduction
to the ventricles.
Propafenone
Most patients who 450-600 mg p.o
undergo Not suitable for patients with
pharmacological cardioversion require continuous
marked structural heart
medical supervision and ECG monitoring during the drugmay
disease; infusion
prolong QRSand for a
period afterwards (usually about half the drug elimination
duration; willhalf-life)
slightly slowto detect
the ventricular
proarrhythmic events such as ventricular proarrhythmia, sinus rate,
node but may
arrest, or
inadvertently increase the
atrioventricular block. ventricular rate due to conversion
to atrial flutter and 1:1 conduction
Several agents are available for pharmacological cardioversion (see Table 10 on
to the ventricles.
page 20).
<<Table 10>>
In clinical practice, amiodarone is the most common agent used in the

management of patients presenting in AF with haemodynamic compromise, as it
appears to have a hybrid effect of rapid reduction in ventricular rate in most
patients with a proportion of these reverting to sinus rhythm over a longer period.
Adapted with modification from the ESC Guidelines for the Management of Atrial
<<Figure 4>>
Fibrillation (2010 Version) (European heart Journal 2010; doi:10.1093/eurheartj/
ehq278)
20
Recent Onset AF (<48 h)
Haemodynamic instability
Yes No
Electrical cardioversion Structural heart disease
21
Yes No
i.v amiodarone oral flecainide

oral propefenone
Figure 4 Direct current conversion and pharmacological cardioversion of recent-onset AF in patients considered for pharmacological cardioversion. AF= atrial
fibrillation
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal 2010; doi:10.1093/eurheartj/ehq278)
In suitable patients with recent-onset AF (generally <48 hours duration), a trial of
In suitable patients
pharmacological with recent-onset
cardioversion to sinus AFrhythm can <48
(generally hours duration),
be offered a trial or
with ecainide of
pharmacological
propafenone (whencardioversion
there is little to or
sinus rhythm canstructural
no underlying be offered
heartwith ecainide
disease) or
or i.v
In suitable patients with recent-onset AF (generally <48 hours duration), a trial of
propafenonepharmacological
amiodarone (when there
thereiscardioversion
islittle or no to
structural underlying
disease)
sinus structural
rhythm (Figure heart
4, page
can be offered disease)
21). orThe
with ecainide i.v
or
amiodaroneconversion
anticipated (when there
propafenone rate
(whenisis50% structural
there little ordisease)
iswithin ~15 – 120(Figure
min.
no underlying 4, heart
structural pagedisease)
21). The
or i.v
anticipated conversion
amiodarone rate
(whenis 50% there within ~15 – disease)
is structural 120 min.(Figure 4, page 21). The
Inanticipated
suitable patients with recent-onset
conversion AF (generally
rate is 50% within <48
~15 – 120 hours duration), a trial of
min.
pharmacological cardioversion to sinus rhythm can be offered with ecainide or
Keypoints
When pharmacological
propafenone (when cardioversion
there is little is or preferred
no underlying and there
structuralis no structural
heart disease)heart
or i.v
When pharmacological
disease, oral ecainide
amiodarone cardioversion
(whenor propafenone
there is is preferred and there
is isrecommended
structural disease) (Figure is
forno4, structural
cardioversion 21).heartof
When36-38 pharmacological cardioversion preferred and there is nopage
structural The
heart
IA
disease,
recent-onset oral AF.ecainide
anticipated or
conversion propafenone is
50% within ~15
rateoris propafenone recommended – 120 min. for cardioversion of
disease, oral ecainide is recommended for cardioversion of
AF.36-38 AF.36-38
recent-onsetrecent-onset
In patients with recent-onset AF and structural heart disease, i.v. amiodarone is
In patients When
recommended.
IAIA with pharmacological
39-41
recent-onset
In patients AFcardioversion
with recent-onset and AF andisstructural
structural preferred
heart heartand disease,
disease,there i.v.
is no structural
amiodarone
i.v. amiodarone heart
isis
disease,39-41 oral ecainide
recommended. 39-41 or propafenone is recommended for cardioversion of
recommended. recent-onset AF. 36-38
Digoxin (Level of Evidence A), verapamil, sotalol, metoprolol (Level of Evidence

Digoxin (Level of Evidence A), verapamil, sotalol, metoprolol (Level of Evidence
Digoxin
IIIABC
B), other(Level
IIIABC InB), of
ȕ-blocking
patients
otherEvidence
agents
with A),(Level
recent-onset
ȕ-blocking verapamil,
agents of
AF(Levelandsotalol,
Evidence structural
of C)metoprolol
Evidence are C) ineffective
heart disease,
are (Level ofinEvidence
i.v.inamiodarone
ineffective converting
converting is
IA
B), other
recent- ȕ-blocking
onset AF toonset
recommended.
recent- agents
sinus 39-41
AF to (Level
rhythm sinusand ofare
rhythm Evidence
notare
and C)recommended.
recommended.
not are ineffective in converting
recent- onset AF to sinus rhythm and are not recommended.
In ICICpatientsDigoxin
Inwith (Level
patients of Evidence
with
a life-threatening A), verapamil,
a life-threatening deterioration sotalol,
deteriorationin metoprolol (Level of Evidence
in haemodynamic
haemodynamic stability
stability
IIIABC B),following
other ȕ-blocking onsetagents (Level of Evidence
In patientsthe
following with
onset a thelife-threatening
of of AF,
AF, emergency emergency
deteriorationelectrical inC)cardioversion
electricalarecardioversion
ineffective in should
haemodynamic converting
should be
stability
be
recent-
performed,onsetirrespective
AF to sinusof rhythm and areofnot
the duration therecommended.
AF.
following the
performed, onset ofof the
irrespective AF, duration
emergency of the electrical
AF. cardioversion should be
performed,Inirrespective
patients
5.1.2.1 of the
with a duration
Pill-in-the-pocket life-threatening
approachof the deterioration
AF. in haemodynamic stability
IC
5.1.2.1 Pill-in-the-pocket
following the onset approachof AF, emergency electrical cardioversion should be
42
5.1.2.1 Pill-in-the-pocket
performed,
The pill-in-the-pocket approach
irrespective ofapproach
the duration of theto
refers AF.outpatient administration of oral
ecainide (200 to 300 mg) 42 or propafenone (450 to 600 mg) to carefully selected
The pill-in-the-pocket approach refers to outpatient administration of oral
patients whose initial therapy in hospital
5.1.2.1
to Pill-in-the-pocket approach
to was
600effective and well tolerated.
42
The pill-in-the-pocket
ecainide (200 300 approach
mg) or propafenone refers to outpatient
(450 mg)administration
to carefully of oral
selected
ecainidewhose
patients (200This to 300
initial
approach mg) or
therapy
could propafenone
bein hospital
considered 42 (450
The pill-in-the-pocket approach refers to outpatient administration was
in to 600
effective
appropriately mg) to
and
selectedcarefully
well selected
tolerated.
patients whoof have
oral
IIaB
patients whose ecainide initial
infrequent (200buttherapy
prolonged
to 300 mg) insymptoms
hospital
or propafenone ofwas effective
paroxysmal
(450 to 600 andtowell
AF (PAF).
mg) tolerated.
carefully selected
This
Keypointsapproach
patientscould be
whose considered
initial therapy in appropriately
in hospital was selected
effective patients
and well who have
tolerated.
This approach
infrequent butTherecould is anbe
prolonged considered
uncommon
symptoms ofinparoxysmal
probability appropriately
of AF revertingAFselected
to AFL with
(PAF). patients who have
this approach and
infrequent butbefore
This approach
prolonged antiarrhythmic
could
symptoms medication
be consideredof paroxysmal inisappropriately
initiated,
AF (PAF).a selected
beta-blocker,patients diltiazem
who have or
IIaB
IIaB verapamil should be given to prevent rapid AV conduction.
There is aninfrequent
uncommon but prolonged
probability symptoms
of AF reverting of paroxysmal to AFLAF (PAF).
with this approach and
There isantiarrhythmic
before an uncommon
Patients probability
medication ofbelow
isAFinitiated,
reverting ato AFL with
beta-blocker, thisanapproach
diltiazem and
or
There is anwith the
uncommon conditionsprobability areAF
of contraindicated
reverting to AFL for such
with this approach:
approach and
before antiarrhythmic
verapamil should
before be
x Those given medication
aged
antiarrhythmic tomore
preventthan 75
medicationisrapid initiated,
years, AVinitiated,
is a beta-blocker,
conduction. a beta-blocker,diltiazem diltiazem or or
verapamil should
verapamil beshould
x Those given
withbe to prevent
AFgivenduration rapid AV
greater
to prevent thanconduction.
rapid 7AVdays,
conduction.
Patients with the conditions below are contraindicated for such an approach:
x NYHA Class III to IV or signs of heart failure on examination,
Patients
x Thosewith thex AF
Patients
aged conditions
withthe
with
more a mean
than below
conditions are
75ventricular
years, below contraindicated
rate
are less than 70for
contraindicated bpm,such
for such an anapproach:
approach:
x Those with
aged Previous
x xThose
AFmore aged myocardial
than
duration more75 than
years,
greater infarction
75
than years, 7 or angina,
days,
Those with Valvular
x xThose
AF withheart disease,greater than 7 days,
AF duration
x NYHA Class IIIduration
to IV or signs greater of than
heart7failure days, on examination,
Cardiomyopathy,
x xNYHA Class III to IV or signs of heart failure on examination,
NYHA
x AF withClass
ax mean III to IV or
ventricular signs rate of less
heartthan failure on examination,
xAF Bundle
with abranch block,
mean ventricular rate less 70 than bpm,
70 bpm,
AF with axmyocardial
x Previous meanKnown
xPrevious ventricular
sick infarction rate
sinus syndrome,
myocardial orless
infarctionangina, than 70 bpm,
or angina,
x Previous myocardial
Valvular xheartValvulardisease,
heart infarction
disease, or angina,
Valvular xheart
x Cardiomyopathy, disease,
Cardiomyopathy,
Cardiomyopathy,
x Bundle x Bundle
branch branch block,
block,
Bundle sick
x Known x Known
branch sinus sick
block, sinus syndrome,
syndrome,
x Low serum
x Known sick sinus syndrome, potassium,
x Or renal or hepatic insufficiency.
With such an approach emergency room visits and hospitalization could

markedly be reduced.
In selected patients with recent-onset AF and no signicant structural heart

IIaB
IIaB disease, a single high oral dose of ecainide or propafenone (the ‘pill-in-the-
pocket’ approach) should be considered, provided this treatment has proven safe
during previous testing in a medically secure environment.42
5.1.3 DIRECT CURRENT CARDIOVERSION

22
DCCV is an effective method of converting AF to sinus rhythm. Successful DCCV
is usually dened as termination of AF, documented as the presence of two or
With such an approach emergency room visits and hospitalization could
In selected patients with recent-onset AF and no signicant structural heart

IaB disease, a single high oral dose of ecainide or propafenone (the ‘pill-in-the-
pocket’ approach) should be considered, provided this treatment has proven safe
during previous testing in a medically secure environment.42
5.1.3 DIRECT CURRENT CARDIOVERSION
DCCV is an effective method of converting AF to sinus rhythm. Successful DCCV

is usually dened as termination of AF, documented as the presence of two or
more consecutive P waves after shock delivery.
5.1.3.1 Procedure
x Low serum potassium,
x Oradequate
Unless renal or hepatic insufficiency.
anticoagulation has been documented for 4 weeks or AF is 48
h from a denite onset, a TOE should be performed to rule out atrial thrombi (see
With such
Figure 9, pagean39).
approach emergency room visits and hospitalization could
A pacing catheter or external pacing pads may be needed if asystole or
In selected occurs.
bradycardia patients with recent-onset AF and no signicant structural heart
IaB disease, a single high oral dose of ecainide or propafenone (the ‘pill-in-the-
Evidence favours the
pocket’ approach) use be
should of biphasic external
considered, debrillators
provided because
this treatment hasofproven
their lower
safe
42
energy requirements
during previous testing inand greatersecure
a medically efficacy compared
environment. with monophasic
debrillators. Trials have demonstrated a signicant increase in the rst shock
5.1.3 DIRECT
success rate ofCURRENT
DCCV for AF CARDIOVERSION
when biphasic waveforms were used.
Currently,
DCCV is antwo conventional
effective method of positions
converting are
AF tocommonly used
sinus rhythm. for electrode
Successful DCCV
placement (see Figure
is usually dened 5). Several
as termination studies
of AF, have shown
documented as thethat anteroposterior
presence of two or
43
electrode placement
more consecutive is more
P waves aftereffective than anterolateral placement. If initial
shock delivery.
shocks are unsuccessful for terminating the arrhythmia, the electrodes should be
repositioned and cardioversion repeated.
5.1.3.1 Procedure
<< Figure
Unless 5>> anticoagulation has been documented for 4 weeks or AF is 48
adequate
h Figure
from5: Patch/paddle
a denite placement for DCCV
onset, a TOE should be performed to rule out atrial thrombi (see
Figure 9, page 39).
The recommended initial energy for synchronised cardioversion (see figure 6) is:
A pacingSternal
patch/paddle
catheter or external pacing pads may be needed if asystole or
bradycardia occurs.
x 200J or greater with monophasic waveform Sternal patch
Evidence
x Apex100J favours the use
or greater withofbiphasic
biphasicwaveform
external debrillators because of their lower
patch/paddle
energy requirements and greater efficacy compared with monophasic
x 10-50J biphasic waveform for AFL
debrillators. Trials have demonstrated a signicant increase in the rst shock
success rate of DCCV for AF when biphasic waveforms were used.
Currently, two conventional positions are commonly used for electrode

placement (see Figure 5). Several studies have shown that anteroposterior
electrode placement is more effective than anterolateral placement.43 If initial
Apex patch
shocks are unsuccessful for terminating the arrhythmia, the electrodes should be
repositioned and cardioversion repeated.
<< Figure 5>>
The recommended initial energy for synchronised cardioversion (see figure 6) is:
x 200J or greater with monophasic waveform

x 100J or greater with biphasic waveform
x 10-50J biphasic waveform for AFL
23
Figure 6 : ECG strip showing synchronized cardioversion
<< Figure 6>>
Outpatient/day care DCCV can be undertaken in patients who are

haemodynamically stable and do not have severe underlying heart disease. At
least 3 h of ECG and haemodynamic monitoring are needed after the procedure,
before the patient is allowed to leave the hospital.
Internal cardioversion may be helpful in special situations, e.g. when a patient

undergoes invasive procedures and cardioversion catheters can be placed
without further vascular access and when implanted debrillation devices are
present.
5.1.3.2 Complications
The risks and complications of cardioversion are associated primarily with

x Thrombo-embolic events,
x Post-cardioversion arrhythmias, and
x The risks of general anesthesia.
The procedure is associated with 1 – 2% risk of thromboembolism, which can be

reduced by adequate anticoagulation in the weeks prior to cardioversion or by
exclusion of left atrium thrombi before the procedure. Skin burns are a common
complication. In patients with sinus node dysfunction, especially in elderly
patients with structural heart disease, prolonged sinus arrest without an adequate
escape rhythm may occur. Dangerous arrhythmias, such as ventricular
tachycardia and brillation, may arise in the presence of hypokalaemia, digitalis
intoxication, or improper synchronization. The patient may become hypoxic or
hypoventilate from sedation, but hypotension and pulmonary oedema are rare.
5.1.3.3 Cardioversion in patients with implanted pacemakers and

debrillators
The electrode paddle should be at least 8 cm from the pacemaker battery, and
the antero-posterior paddle positioning is recommended. Biphasic shocks are
preferred because they require less energy for AF termination. In pacemaker-
dependent patients, an increase in pacing threshold should be anticipated. In the
absence of a pacemaker programmer, a pacing magnet may be placed over the
pacemaker generator pocket to provide temporary pacing support. These
patients should be monitored carefully. After cardioversion, the device should be
interrogated and evaluated to ensure normal function.
5.1.3.4 Recurrence after cardioversion
Recurrences after DCCV can be divided into three phases:

(1) Immediate recurrences, which occur within the rst few minutes after DCCV.
(2) Early recurrences, which occur during the rst 5 days after DCCV.
24
(3) Late recurrence, which occur thereafter.
Factors that predispose to AF recurrence are age, AF duration before

(3) Late recurrence, which occur thereafter.
cardioversion, number of previous recurrences, an increased LA size or reduced
LA function,Factors
and the presence
that predispose of coronary heart disease
to AF recurrence or pulmonary
are age, AF duration or mitral
before
valve disease. Atrial ectopic
cardioversion, numberbeats with recurrences,
of previous a long – short sequence,
an increased LA sizefaster heart
or reduced
rates, and variations
LA function,inand
atrial
theconduction
presence of increase the risk
coronary heart of AForrecurrence.
disease pulmonary or mitral
Pre-treatment with
valve antiarrhythmic
disease. drugs
Atrial ectopic such
beats withas amiodarone,
a long sotalol, ecainide,
– short sequence, faster heart
44-46
and propafenone increases
rates, and variationsthe likelihood
in atrial of restoration
conduction increase theofrisk
sinus rhythm.
of AF recurrence.
Some highlyPre-treatment
symptomatic withpatients
antiarrhythmic
in whomdrugs AFsuch as amiodarone,
occurs infrequently sotalol,
(e.g.ecainide,
once or
44-46
andstrongly
twice a year) propafenone
preferincreases the likelihood
to undergo repeated of restoration of sinus as
cardioversions rhythm.
a long-term
Some highly symptomatic patients in whom AF occurs infrequently
rhythm control strategy, rather than opting for rate control or other rhythm control (e.g. once or
twice athey
modalities which year)may
strongly
nd prefer to undergo repeated cardioversions as a long-term
uncomfortable.
rhythm control strategy, rather than opting for rate control or other rhythm control
modalities which they may nd uncomfortable.
KeypointsDCCV is recommended when a rapid ventricular rate does not
Immediate
C respond promptly to pharmacological
Immediate measures
DCCV is recommended wheninapatients with AF rate
rapid ventricular and does
ongoing
not
ICIC
myocardial ischaemia,
respond symptomatic
promptly hypotension,
to pharmacological angina,
measures or heart
in patients withfailure.
AF and ongoing
myocardial ischaemia, symptomatic hypotension, angina, or heart failure.
Immediate DCCV is recommended for patients with AF involving pre-excitation
B IB rapid Immediate
when DCCV
tachycardia is recommended instability
or haemodynamic for patientsiswith 47
AF involving
present. pre-excitation
IB 47
when rapid tachycardia or haemodynamic instability is present.
Elective DCCV should be considered in order to initiate a long-term rhythm
IaB Elective DCCV should be considered in order to initiate a long-term rhythm
IIaB management
control
IIaB strategy for patients with AF. 41,43,48
41,43,48
control management strategy for patients with AF.
Pre-treatment with amiodarone,
Pre-treatment ecainide,
with amiodarone, propafenone
ecainide, or or
propafenone sotalol
sotalol should
should be
be
IaB IIaB
considered to enhance 44-46
IIaB considered to success of DCCV
enhance success and prevent
of DCCV recurrent
and prevent AF.AF.
recurrent 44-46
IbC Repeated
IIbC
IIbC DCCV
Repeatedmay be considered
DCCV in highly
may be considered symptomatic
in highly patients
symptomatic refractory
patients refractory to
to
other therapy.
other therapy.
Pre-treatment
IIbC Pre-treatment with ȕ-blockers,
with ȕ-blockers, diltiazem
diltiazem or verapamil
or verapamil maymay
be be consideredfor
considered forrate
rate
IbC IIbC control,the
although the of
efficacy
control, although efficacy theseofagents
these agents in enhancing
in enhancing success
success of ofDCCV
DCCVor
or
preventing
preventing early early recurrence
recurrence of AF isofuncertain.
AF is uncertain.
IIIC
IIIC DCCV is contraindicated in patients with digitalis toxicity.
IIC DCCV is contraindicated in patients with digitalis toxicity.
5.1.3 Antithrombotic therapy for acute-onset AF
Please go to section 6, page 26.
25
6. MANAGEMENT - PREVENTION OF THROMBOEMBOLISM
6.1 RISK STRATIFICATION FOR STROKE
Assessment of thromboembolic risk or risk stratification allows the clinician to

consider anticoagulant treatment for those people who are at an increased risk of
stroke.
Two recent systematic reviews have addressed the evidence base for stroke risk
factors in AF,49,50 and concluded that prior stroke/TIA/thrombo-embolism, age,
hypertension, diabetes, and structural heart disease are important risk factors.
The presence of moderate to severe LV systolic dysfunction TTE is the only
independent echocardiographic risk factor for stroke on multivariable analysis.
On TOE, the presence of LA thrombus, complex aortic plaques, spontaneous
echo-contrast and low LAA velocities are independent predictors of stroke and
thrombo-embolism.
Patients with paroxysmal AF should be regarded as having a stroke risk similar

to those with persistent or permanent AF, in the presence of risk factors.
Patients aged less than 60 years, with ‘lone AF’, i.e. no clinical history or physical
evidence of cardiovascular disease, carry a very low cumulative stroke risk,
estimated to be 1.3% over 15 years.
The various stroke clinical risk factors has led to publication of various stroke
schemes.51,52 The simplest risk assessment scheme is the CHADS2 score and as
shown in Table 11, has good stroke correlation. The CHADS2 [cardiac failure,
hypertension, age, diabetes, stroke (doubled)] risk index evolved from the AF
Investigators and Stroke Prevention in Atrial Fibrillation (SPAF) Investigators
criteria, and is based on a point system in which 2 points are assigned for a
history of stroke or TIA and 1 point each is assigned for age >75 years, a history
of hypertension, diabetes, or recent cardiac failure.51
The CHADS2 stroke risk stratication scheme should be used as an initial, rapid,
and easy-to-remember means of assessing stroke risk. In patients with a
CHADS2 score 2, chronic OAC therapy with a VKA is recommended in a dose-
adjusted approach to achieve an international normalized ratio (INR) target of 2.5
(range, 2.0 – 3.0), unless contraindicated.6,52
<<Table 11>>
A comparison of the 12 published risk-stratication49 schemes to predict stroke in

patients with non-valvular AF found that most had very modest predictive value
for stroke and the proportion of patients assigned to individual risk categories
varied widely across the schemes. The CHADS2 score categorized most subjects
as ‘moderate risk’. The choice of antithrombotic (anticoagulants or antiplatelets)
26
6.1 RISK STRATIFICATION FOR STROKE
Assessment of thromboembolic risk or risk stratification allows the clinician to

consider anticoagulant treatment for those people who are at an increased risk of
stroke.
Two recent systematic reviews have addressed the evidence base for stroke risk
49,50
factors
Table in AF,2 score and
11: CHADS concluded
and strokethat prior stroke/TIA/thrombo-embolism, age,
rate
hypertension, diabetes, and structural heart disease are important risk factors.
The presence of moderate to severe LV systolic dysfunction TTE is the only
independent echocardiographic risk factor for strokeAdjusted strokeanalysis.
on multivariable rate
Patientscomplex aortic plaques,
On TOE, the presence of LA thrombus, (%/year)spontaneous
a
CHADS2 Score
echo-contrast and low LAA velocities are independent predictors of stroke and
(n=1733) (95% confidence
thrombo-embolism.
interval)
Patients with paroxysmal AF should be regarded as having a stroke risk similar
to those with0 persistent or permanent AF, in the presence of1.9
120 risk(1.2-3.0)
factors.
Patients aged
1 less than 60 years, with ‘lone AF’, i.e. no clinical history or physical
463 2.8 (2.0-3.8)
evidence of cardiovascular disease, carry a very low cumulative stroke risk,
estimated to be 1.3% over 15 years.
2 523 4.0 (3.1-5.1)
The various stroke clinical risk factors has led to publication of various stroke
schemes.51,523 The simplest risk assessment
337 scheme is the 5.9 CHADS 2 score and as
(4.6-7.3)
shown in Table 11, has good stroke correlation. The CHADS2 [cardiac failure,
hypertension, age, diabetes, stroke (doubled)] risk index evolved from the AF
Investigators4 and Stroke Prevention 220in Atrial Fibrillation8.5 (6.3-11.1)
(SPAF) Investigators
criteria, and is based on a point system in which 2 points are assigned for a
history of stroke
5 or TIA and 1 point each65 is assigned for age 12.5>75 years, a history
(8.2-17.5)
of hypertension, diabetes, or recent cardiac failure.51
The CHADS62 stroke risk stratication 5scheme should be 18.2 used (10.5-27.4)
as an initial, rapid,
and easy-to-remember means of assessing stroke risk. In patients with a
CHADS2 score 2, chronic OAC therapy with a VKA is recommended in a dose-
a
adjusted approach
The adjusted stroke rateto achieve
was an international
derived from the multivariablenormalized rationo
analysis assuming (INR) target
aspirin usage;of 2.5
these
stroke rates are based on data from a cohort of hospitalized
6,52 AF patients, published in 2001, with low
(range, 2.0 – 3.0), unless contraindicated.
numbers in those with a CHADS2 score of 5 and 6 to allow an accurate judgement of the risk in these
patients. Given that stroke rates are declining overall, actual stroke rates in contemporary non-
51
hospitalized cohorts may also vary from these estimates. Adapted from Gage F et al. AF = atrial
<<TableCHADS
fibrillation; 11>>2 = cardiac failure, hypertension, age, diabetes, stroke (doubled).
A comparison of the 12 published risk-stratication49 schemes to predict stroke in

patients with non-valvular AF found that most had very modest predictive value
for stroke and the proportion of patients assigned to individual risk categories
varied widely across the schemes. The CHADS2 score categorized most subjects
as ‘moderate risk’. The choice of antithrombotic (anticoagulants or antiplatelets)
for the ‘moderate risk’ group was at best uncertain.
Several published analyses 49,50,53-55 have found even patients at ‘moderate risk’
(currently dened as CHADS2 score =1, i.e. one risk factor) still derive signicant
benet from OAC over aspirin use, often with low rates of major haemorrhage.
Importantly, prescription of an antiplatelet agent was not associated with a lower
risk of adverse events.
Also, the CHADS2 score does not include many stroke risk factors, and other
‘stroke risk modiers’ need to be considered in a comprehensive stroke risk
assessment (see Table 11, page 27).
Rather than the use of the ‘low’, ‘moderate’, and ‘high’ risk characterization that
only showed a modest predictive value, this guideline has adopted and recognize
that risk is a continuum. A risk factor-based approach for a more detailed stroke
risk assessment is encouraged for recommending the use of antithrombotic
therapy.
27
The risk factor-based approached for patients with non-valvular AF have been
given an acronym, CHA2DS2VASc and the schema is based on two groups of
assessment (see Table 11, page 27).
Rather than the use of the ‘low’, ‘moderate’, and ‘high’ risk characterization that
only showed a modest predictive value, this guideline has adopted and recognize
that risk is a continuum. A risk factor-based approach for a more detailed stroke
risk assessment is encouraged for recommending the use of antithrombotic
therapy.
The risk factor-based approached for patients with non-valvular AF have been
given an acronym, CHA2DS2VASc and the schema is based on two groups of
risk factors:
x Major risk factors - prior history of stroke, TIA or thromboembolism

and/or age 75 or older
x Clinically relevant ‘non-major’ risk factors - hypertension, heart failure

(EF 40%), diabetes, age 65–74 years, female gender, and vascular
disease (myocardial infarction, complex aortic plaques and PAD).
The risk may be calculated based on a point system in which 2 points are
allocated for each ‘Major risk factors’; and 1 point each is assigned for
‘Clinically relevant ‘non major’ risk factors’ (see Table 11 on page 27).
6.2 STRATEGIES FOR THROMBOEMBOLIC PROPHYLAXIS
The CHADS2 stroke risk stratication scheme should be used as a simple initial
(and easily remembered) means of assessing stroke risk, particularly suited to
primary care doctors and non-specialists.
In patients with a CHADS2 score of 2, chronic OAC therapy, e.g. with a VKA, is
recommended in a dose adjusted to achieve an INR value in the range of 2.0 –
3.0, unless contraindicated.
In patients with a CHADS2 score of 0 – 1, or where a more detailed stroke risk

assessment is indicated, it is recommended to use a more comprehensive risk
factor-based approach incorporating other risk factors for thrombo-embolism (see
Table 12 and Figure 7).56-58
In all cases where OAC is considered, a discussion of the pros and cons with the
patient, and an evaluation of the risk of bleeding complications, ability to safely
sustain adjusted chronic anticoagulation, and patient preferences are necessary.
In some patients, for example, women aged less than 65 years with no other risk
factors (i.e. a CHA2DS2VASC score of 1) aspirin rather than OAC therapy may be
considered.
<<Table 12>>
<<Figure 7>>
28
Table 12. CHA2DS2VASC Score, stroke rate and approach to thromboprophylaxis in patients with AF
a) Risk Factors for Stroke and thrombo embolism in non-valvular AF

Major' risk factors Clinically relevant non-major' risk
factors
Heart failure or moderate to

severe LV systolic dysfunction
Previous stroke, TIA
(e.g, LV EF 40%)
or systemic embolism
Hypertension - Diabetes mellitus
Age 75 years
Female sex - Age 65-74 years
Vascular diseasea
b) Risk factor-based approach expressed as a point based

scoring system, with the acronym CHA2DS2-VASc
(Note: maximum score is 9 since age may contribute 0,1 or 2 points)
Risk factor Score
Congestive heart failure/LV dysfunction 1

Hypertension 1
Age 75 2
Diabetes mellitus 1
Stroke/TIA/thrombo-embolism 2
Vascular disease 1
Age 65-74 1
Sex category (i.e, female sex) 1
Maximum score 9
c) Adjusted stroke rate according to CHA2DS2-VASc score
Adjusted stroke rate
CHA2DS2-VASC score Patients (n=7329) b
(%/year)
0 1 0%
1 422 1.30%
2 1230 2.20%
3 1730 3.20%
4 1718 4.00%
5 1159 6.70%
6 679 9.80%
7 294 9.60%
8 82 6.70%
9 14 15.20%
Approach to thromboprophylaxis in patients with AF
CHA2DS2-VASC Recommended
Risk category
score antithrombotic therapy
One 'major' risk factor or 2

c
'clinically relevant non-major risk 2 OAC
factors
Either OAC or aspirin 75-

One 'clinically relevant non-major'
1 325 mg daily. Preferred:
risk factor
OAC rather than aspirin
Either aspirin 75-325mg

daily or no antithrombotic
No risk factors 0 therapy. Preferred: no
antithrombotic therapy
rather than aspirin
29
See text for definitions.
a
Prior myocardial infarction, peripheral artery disease, aortic plaque. Actual rates of stroke in contemporary
cohorts may vary from these estimates.
b
Based on Lip et al.54
AF=atrial fibrillation; EF =ejection fraction (as documented by echocardiography, radionuclide
ventriculography, cardiac catheterization, cardiac magnetic resonance imaging, etc.); LV=left ventricular;
TIA=transient ischaemic attack.
CHA2DS2-VASC=cardiac failure, hypertension, age 75 (doubled), diabetes, stroke (doubled)-vascular
disease, age 65–74 and sex category (female); INR=international normalized ratio; OAC=oral
anticoagulation, such as a vitamin K antagonist (VKA) adjusted to an intensity range of INR 2.0–3.0 (target
2.5).
c
OAC, such as a VKA, adjusted to an intensity range of INR 2.0–3.0 (target 2.5). New OAC drugs, which
may be viable alternatives to a VKA, may ultimately be considered. For example, should both doses of
dabigatran etexilate receive regulatory approval for stroke prevention in AF, the recommendations for
thromboprophylaxis could evolve as follows considering stroke and bleeding risk stratification:
(a) Where oral anticoagulation is appropriate therapy, dabigatran may be considered, as an alternative to
adjusted dose VKA therapy. (i) If a patient is at low risk of bleeding (e.g. HAS-BLED score of 0–2; see Table
14 for HAS-BLED score definition), dabigatran 150 mg b.i.d. may be considered, in view of the improved
efficacy in the prevention of stroke and systemic embolism (but lower rates of intracranial haemorrhage and
similar rates of major bleeding events, when compared with warfarin); and (ii) If a patient has a measurable
risk of bleeding (e.g. HAS-BLED score of 3), dabigatran etexilate 110 mg b.i.d. may be considered, in view
of a similar efficacy in the prevention of stroke and systemic embolism (but lower rates of intracranial
haemorrhage and of major bleeding compared with VKA). (b) In patients with one ‘clinically relevant non-
major’ stroke risk factor, dabigatran 110 mg b.i.d. may be considered, in view of a similar efficacy with VKA
in the prevention of stroke and systemic embolism but lower rates of intracranial haemorrhage and major
bleeding compared with the VKA and (probably) aspirin. (c) Patients with no stroke risk factors (e.g.
CHA2DS2-VASC = 0) are clearly at so low risk, either aspirin 75–325 mg daily or no antithrombotic therapy is
recommended. Where possible, no antithrombotic therapy should be
considered for such patients, rather than aspirin, given the limited data on the benefits of aspirin in this
patient group (i.e., lone AF) and the potential for adverse effects, especially bleeding.
+
CHADS2 score 2
+
CHADS2 Score
Risk Factors Score
No Yes Congestive heart failure 1
Hypertension 1
Consider other risk factors* Age 75 1
Age 75 years Diabetes 1
Stroke/TIA 2
*Other clinically relevant non-

No Yes major risk factor:
Age 65-74, female sex, vascular
disease
2 other risk factors*
No Yes OAC
1 other risk factor*
Yes OAC (or aspirin)
No Nothing (or aspirin)
Figure 7 Clinical flowchart for the use of oral anticoagulant for stroke prevention in AF. AF = atrial fibrillation; OAC = oral
anticoagulant; TIA = transient ischaemic attack.
7 Clinical flowchart for the use of oral anticoagulant for stroke prevention in AF. AF = atrial fibrillation; OAC = oral anticoagulant; TIA = transient ischaemic attack. A full
ption of theAdapted
CHADS2 fromcan bethe
found on page
ESC ?
Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal
2010; doi:10.1093/eurheartj/ehq278)
30
6.3 ANTITHROMBOTIC THERAPY
6.3.1 ANTICOAGULATION WITH VITAMIN K ANTAGONISTS
There were6.3 6ANTITHROMBOTIC

large randomizedTHERAPY
trials, both primary and secondary prevention,
that provided an extensive and robust evidence base for VKA therapy in AF.
6.3.1 ANTICOAGULATION WITH VITAMIN K ANTAGONISTS
55
There were adjusted-dose
In a meta-analysis VKAtrials,
6 large randomized (international
both primary normalized ratio prevention,
and secondary [INR] 2-3)
showed athat
significant
provided 64% risk reduction
an extensive ofevidence
and robust stroke andbase26% risktherapy
for VKA reduction
in AF.of all
53,59-63
cause mortality in patients with non valvular AF.
In a meta-analysis55 adjusted-dose VKA (international normalized ratio [INR] 2-3)
showed a significant
Risk of intracranial hemorrhage 64%was
risk reduction of stroke 53,59-63
small (0.3-1.8%). and 26% Whenrisk reduction of all
VKA is given
to elderlycause mortality
patients in patients
with atrial with non valvular
fibrillation, AF.53,59-63
hypertension must be managed
aggressively. 53,59-63
Risk of intracranial hemorrhage was small (0.3-1.8%). When VKA is given
to elderly patients with atrial fibrillation, hypertension must be managed
Antithrombotic
Keypoints therapy is recommended for patients with atrial utter as for those
aggressively.
IC with AF.
Antithrombotic therapy is recommended for patients with atrial utter as for those
IC
IC with AF.
The selection of antithrombotic therapy should be considered using the same
IIaA
criteria irrespective of the pattern of AF (i.e. paroxysmal, persistent, or
The selection of antithrombotic therapy should be considered using the same
49,50
permanent).
IIaA
IIaA
criteria irrespective of the pattern of AF (i.e. paroxysmal, persistent, or
permanent).49,50
Antithrombotic therapy to prevent thrombo-embolism is recommended for all
IA patients with AF, except
Antithrombotic in those
therapy at low risk
to prevent (lone AF, aged
thrombo-embolism <65 years, orforwith
is recommended all
IAIA
contraindications). 49,50,64
patients with AF, except in those at low risk (lone AF, aged <65 years, or with
contraindications).49,50,64
It is recommended that the selection of the antithrombotic therapy should be
IA based
It is recommended that the selection of the antithrombotic therapy should be
IAIA upon the absolute risks of stroke/ thrombo-embolism
based upon the absolute risks of stroke/49,50,51
and bleeding, and
thrombo-embolism and bleeding, and
the relative
therisk and risk
relative benet for a given
and benet patient.
for a given patient.49,50,51
The
IA
CHADS [cardiac
The2 CHADS failure, failure,
2 [cardiac hypertension, age,age,
hypertension, diabetes,
diabetes,stroke
stroke(doubled)]
(doubled)]
IA IA
score is score
recommended as a as
is recommended simple initialinitial
a simple (easily remembered)
(easily remembered) means
means of
assessing stroke risk in 51 AF. 51
non-valvular
assessing stroke risk in non-valvular AF.
For the patients with a CHADS score of 2, chronic OAC therapy with a VKA is
ForIAthe patients
IA with a CHADS2 score2 ofregimen 2, chronic OAC therapy with a VKA is
IA recommended in a dose-adjusted to achieve an INR range of 2.0–3.0
recommended(targetin a dose-adjusted
2.5), regimen
unless contraindicated. to achieve an INR range of 2.0–3.0
49,50,55
49,50,55
(target 2.5), unless contraindicated.
IA
IA For a more detailed or comprehensive stroke risk assessment in AF (e.g. with
For a moreCHADS 2 scores
detailed 0–1), a risk factor-based
or comprehensive strokeapproach is recommended,
risk assessment in AF considering
(e.g. with
IA ‘major’ and ‘clinically factors.53
CHADS2 scores 0–1), a risk relevant non-major’
factor-based stroke is
approach riskrecommended, considering
53
‘major’ and ‘clinically relevant non-major’ stroke risk factors.
IA
IA Patients with 1 ‘major’ or > 2 ‘clinically relevant non-major’ risk factors are high
risk, and OAC therapy is recommended, unless contraindicated.53
IA Patients with 1 ‘major’ or > 2 ‘clinically relevant non-major’ risk factors are high
53
risk, and OAC therapy
Patients is recommended,
with one ‘clinically relevantunless contraindicated.
non-major’ risk factor are at intermediate risk
and antithrombotic therapy is recommended, either as:
IA
IA i. VKA therapy53 or
IB
IB ii. aspirin 75–325 mg daily50
IB Patients with no risk factors are at low risk (essentially patients aged <65 years
IB
with lone AF, with none of the risk factors) and the use of either aspirin 75–325
mg daily or no antithrombotic therapy is recommended.53
Most patients with one ‘clinically

31 relevant non-major’ risk factor should be
IIaA considered for OAC therapy (e.g. with a VKA) rather than aspirin, based upon an
assessment of the risk of bleeding complications, the ability to safely sustain
IA andi.antithrombotic or
VKA therapy therapy is recommended, either as:
IB ii. aspirin 75–325 mg daily50
IA i. VKA therapy53 or
IB Patients with75–325
ii. aspirin no risk mg
factors
dailyare
50 at low risk (essentially patients aged <65 years
IB
with lone AF, with none of the risk factors) and the use of either aspirin 75–325
mg daily or no antithrombotic therapy is recommended.53
Patients with no risk factors are at low risk (essentially patients aged <65 years
IB Most patients withnone
oneof‘clinically relevantandnon-major’
with lone AF, with the risk factors) the use ofrisk factor
either should
aspirin be
75–325
IIaA
IIaA considered for antithrombotic
OAC therapy (e.g. withisa recommended.
VKA) rather than
53 aspirin, based upon an
mg daily or no therapy
assessment of the risk of bleeding complications, the ability to safely sustain
49,50
adjusted
Most chronicwith
patients anticoagulation,
one ‘clinicallyandrelevant
patient preferences.
non-major’ risk factor should be
IIaA considered for OAC therapy (e.g. with a VKA) rather than aspirin, based upon an
IA Anticoagulation
assessment withrisk
of the VKAof isbleeding
also recommended
complications,forthe
patients
ability with more sustain
to safely than 1
IA
moderatechronic
adjusted risk factor (female gender,
anticoagulation, and age between
patient 65-74, 49,50
preferences. hypertension, diabetes
mellitus, vascular disease, HF, or impaired LV systolic function [ejection fraction
3,4,65
35% or less or fractional
Anticoagulation with VKA shortening less than 25%]).
is also recommended for patients with more than 1
IA
moderate risk factor (female gender, age between 65-74, hypertension, diabetes
6.3.2 OPTIMAL INTERNATIONAL
mellitus, vascular disease, NORMALIZED
HF, or impairedRATIO
LV systolic function [ejection fraction
35% or less or fractional shortening less than 25%]).3,4,65
The level of anticoagulation is expressed as the INR and is derived from the ratio between
the actual
6.3.2 prothrombin
OPTIMAL time and thatNORMALIZED
INTERNATIONAL of a standardized control serum.
RATIO
level ofFor
TheIA patients with is
anticoagulation non-valvular
expressed AF, it isINR
as the recommended thatfrom
and is derived the target intensity
the ratio betweenof
Keypoints anticoagulation
the actual prothrombin timewith
and athat
VKAof ashould to maintain
standardized anserum.
control INR range of 2.0-3.0 (target
Patients
49,50,64
2.5) with one ‘clinically relevant non-major’ risk factor are at intermediate risk
and
Forantithrombotic therapy is recommended,
patients with non-valvular either as: that the target intensity of
AF, it is recommended
IA
IA For patients withwith AF awho have mechanical heartan valves, it is recommended that
anticoagulation VKA should to maintain INR range of 2.0-3.0 (target
IB the target
2.5) 49,50,64 intensity of anticoagulation with a VKA should be based on the type
IA andi. VKA
position
53
of theorprosthesis, maintaining an INR of at least 2.5 in the mitral
therapy
position
For and at
patients least
with AF 2.0
whoforhave
an aortic valve.64,66
mechanical heart valves, it is recommended that
IB
IB ii. aspirin 75–325 daily50
mganticoagulation
IB the target intensity of with a VKA should be based on the type
<<Figure 8>>
and position of the prosthesis, maintaining an INR of at least 2.5 in the mitral
position and at least 2.0 for an aortic valve.64,66
Patients with no risk factors are at low risk (essentially patients aged <65 years
IB
Figure 8:
8: Adjusted
Adjusted odds ratios for ischaemic stroke and intracranial bleeding in relation
relation to intensity
intensity of
Figure A target
with lone
<<Figure oddsINR
AF,8>> of 2.5
with
ratios none
for (target range
of the
ischaemic riskoffactors)
stroke 2.0 intracranial
and to and
3.0) the
is safe
usefor
of primary
bleeding either
in prevention
aspirin
to 75–325 in
of
IA
anticoagulation
older
mg
anticoagulation in
dailyrandomised
in patients
randomised trials
more of
of antithrombotic
than
or no antithrombotic
trials 75 years,
therapy istherapy
unless
antithrombotic for
for people
contraindicated.
recommended.
therapy
53 67 atrial fibrillation.
people with
with atrial fibrillation.
Figure 8: Adjusted odds ratios for ischaemic stroke and intracranial bleeding in relation to intensity of
anticoagulation
The
Most inmajor
randomised
A target INR
patients trials
bleeding
ofwith
2.5 of antithrombotic
rate for
(target
one range
‘clinically therapy
5 randomized
ofrelevant
2.0 for
3.0) people
to clinical
is safe with
trials
non-major’ was
for atrial
1.2%
primary
risk fibrillation.
per
factor year. Inbe
prevention
should 2
in
IIaAIA time-dependent
older patients
considered more
for OAC INRthananalyses
75 years,
therapy of aanticoagulation
unless
(e.g. with in 67
contraindicated.
VKA) rather than elderlybased
aspirin, AF upon
cohorts,
an
intracranial bleed
assessment of theincreased with INRcomplications,
risk of bleeding values over 3.5 thetoability
4.0, and there was
to safely no
sustain
49,50
The major
adjusted bleeding
chronic rate for 5 randomized
anticoagulation, and patientclinical trials was 1.2% per year. In 2
preferences.
time-dependent INR analyses of anticoagulation in elderly AF cohorts,
intracranial bleed
Anticoagulation increased
with with INR
VKA is also values overfor
recommended 3.5patients
to 4.0, and
with there
more was
thanno1
IA
moderate risk factor (female gender, age between 65-74, hypertension, diabetes
mellitus, vascular disease, HF, or impaired LV systolic function [ejection fraction
35% or less or fractional shortening less than 25%]).3,4,65
6.3.2 OPTIMAL INTERNATIONAL NORMALIZED RATIO
The level of anticoagulation is expressed as the INR and is derived from the ratio between
the actual prothrombin time and that of a standardized control serum.
For patients with non-valvular AF, it is recommended that the target intensity of
IA
anticoagulation with a VKA should to maintain an INR range of 2.0-3.0 (target
2.5) 49,50,64
For patients with AF who have mechanical heart valves, it is recommended that
IB the target intensity of anticoagulation with a VKA should be based on the type
and position of the prosthesis, maintaining an INR of at least 2.5 in the mitral
Reproduced
Reproduced with
with permission
permission from
from Ann
Ann Intern
Intern Med.
Med. Hylek
Hylek E,
E, Singer
Singer D.
D. Risk
Risk factors
factors for
for intracranial
intracranial
hemorrhage in
in outpatients
<<Figure
hemorrhage 8>> taking
outpatients taking warfarin.
warfarin. Ann
Ann Intern
Intern Med
Med 1994;120:897-902.
1994;120:897-902.
Reproduced with permission from Ann Intern Med. Hylek E, Singer D. Risk factors for intracranial
hemorrhage in outpatients taking warfarin. Ann Intern Med 1994;120:897-902.
IA A target INR of 2.5 (target range of 2.0 to 3.0) is safe for primary prevention in
IA older patients more than 75 years, unless contraindicated.67
The major bleeding rate for 5 randomized clinical trials was 1.2% per year. In 2
32 values over 3.5 to 4.0, and there was no
intracranial bleed increased with INR
<<Figure 8>>
A target INR of 2.5 (target range of 2.0 to 3.0) is safe for primary prevention in
IA older patients more than 75 years, unless contraindicated.67
The major bleeding rate for 5 randomized clinical trials was 1.2% per year. In 2
intracranial bleed increased with INR values over 3.5 to 4.0, and there was no
increment with values between 2.0 and 3.0 compared with lower INR levels. (See
Figure 6, page 24)
For guide of using VKA in daily practice please refer to Appendix C, page 74.
6.3.2.1 Point-of-care testing

increment with values and self-monitoring
between of anticoagulation
2.0 and 3.0 compared with lower INR levels. (See
increment with 24)
Figure 6, page values between 2.0 and 3.0 compared with lower INR levels. (See
Figure 6, page 24)
Self-monitoring may be considered if preferred by a patient who is both physically
For guideable
and cognitively of using VKA in daily
to perform practice please refer
the self-monitoring test,to Appendix C, a
page 74.
For guide of using VKA in daily practice please refer to and, if not,
Appendix designated
C, page 74.
carer could help. Appropriate training by a competent healthcare professional is
6.3.2.1 Point-of-care testing and self-monitoring of anticoagulation
important, and Point-of-care
6.3.2.1 the patient should
testingremain in contact with
and self-monitoring ofaanticoagulation
named clinician.
These point-of-care
Self-monitoringdevices may alsoif be
may be considered usefulbyin
preferred remote
a patient who places
is both and allow
physically
patients Self-monitoring
easy
and access may
cognitively be considered
to testing.
able to perform the ifself-monitoring
preferreddevices
Point-of-care by a test,
patient who
also
and, is both
ifrequire
not, physically
adequate
a designated
and cognitively
quality assurance
carer couldand able to perform
help.calibration. the self-monitoring test, and, if not, a designated
Appropriate training by a competent healthcare professional is
carer couldand
important, help.
theAppropriate training
patient should byina contact
remain competent
withhealthcare professional is
a named clinician.
important, and the patient
These point-of-care should
devices mayremain in
becontact
useful with
also THROMBIN a named
in INHIBITORS
remote clinician.
places and allow
6.3.3 ANTICOAGULATION
These WITH DIRECT
patientspoint-of-care
easy accessdevices may Point-of-care
to testing. also be useful in remote
devices also places
require and allow
adequate
patients easy access
quality assurance to testing. Point-of-care devices also require adequate
and calibration.
Dabigatran etexilate
quality is and
assurance an calibration.
oral prodrug that is rapidly converted by a serum
esterase6.3.3
to dabigatran, a potent, WITH
ANTICOAGULATION direct,DIRECT
competitive
THROMBINinhibitor of thrombin. It does
INHIBITORS
6.3.3
not require ANTICOAGULATION
regular monitoring andWITH
has aDIRECT
serumTHROMBIN INHIBITORS
half-life of 12 to 17 hours.
Dabigatran etexilate is an oral prodrug that is rapidly converted by a serum
Dabigatran etexilate is aanpotent,
The Randomized Evaluation of oral
esterase to dabigatran, prodrug
Long-term that is rapidly
direct, competitive
Anticoagulation converted
inhibitor of by a. Itserum
thrombin
Therapy (RE-LY)
does
esterase
not requireto regular
dabigatran, a potent,
monitoring and direct,
a competitive
hasfixed
serum inhibitor
half-life of of 17
12 to thrombin
hours. . It does
was a randomized trial comparing two doses of dabigatran,
not require regular monitoring and has a serum half-life of 12 to 17 hours. given in a
blinded manner, with open-label use of VKA in patients with atrial fibrillation.58
The Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY)
Dabigatran
The 110 mg b.i.d. was non-inferior
Randomized to VKA for the prevention of stroke
was a randomizedEvaluation of Long-term
trial comparing two fixedAnticoagulation Therapygiven
doses of dabigatran, (RE-LY)in a
and systemic
was a embolism
blinded randomized with
manner, withtrial
lower rates
comparing
open-label usetwo
offixed
major
of VKA
bleeding,
indoses
patients
whilst dabigatran
of dabigatran, given in 58
with atrial fibrillation. a
58
150 mgDabigatran
b.i.d. manner,
blinded was110 associated
withb.i.d.
mg waswith
open-label uselower
of VKA
non-inferior torates
in of the
patients
VKA for stroke
with and
atrial
prevention systemic
fibrillation.
of stroke
embolismDabigatran
andwith 110 mg
similarembolism
systemic b.i.d. was
rates of with non-inferior
major haemorrhage,
lower to VKA
rates of major for
comparedthe prevention
bleeding, with
whilstVKA.of stroke
dabigatran
and
150 systemic
mg b.i.d.embolism with lowerwith
was associated rates of major
lower ratesbleeding, whilst
of stroke anddabigatran
systemic
150 mg b.i.d.
embolism was associated
with similar with
rates of major lower ratescompared
haemorrhage, of strokewith
and systemic
VKA.
embolism with similar rates of major haemorrhage, compared with VKA.
Where oral anticoagulation is appropriate therapy for patients with non-valvular
Keypoints
IB AF, dabigatran may be considered, as an alternative to adjusted dose VKA
Where oral anticoagulation is appropriate therapy for patients with non-valvular
therapy.
IB Where oral anticoagulation is appropriate therapy for patients with non-valvular
IBIB AF, dabigatran may be considered, as an alternative to adjusted dose VKA
AF, dabigatran may be considered, as an alternative to adjusted dose VKA
therapy.
There is therapy.
currently no evidence to support the use of dabigatran for AF associated
with valve disease,
There prosthetic
is currently valve,toinsupport
no evidence pregnancy and
the use of chronic renal
dabigatran failure.
for AF associated
There
with is currently
valve disease,noprosthetic
evidencevalve,
to support the use of
in pregnancy anddabigatran for AF
chronic renal associated
failure.
with valve disease, prosthetic valve, in pregnancy and chronic renal failure.
Patients with AF who are indicated for OAC but are unwilling to go on VKA
IB Patients with AF who arechronic
indicated
because
IB of the inconvenience,
Patients with AF oralfor
who are indicated
OAC but are therapy
anticoagulant
for
unwillingwith
to go on VKA
dabigatran
IBIBmg twice
150 because of
daily the
mayinconvenience, chronic
be considered, oralOAC
unless
but are unwilling
anticoagulant to go
therapy with on VKA
dabigatran
because of the inconvenience, chronic oral contraindicated.
anticoagulant therapy with dabigatran
150 mg twice daily may be considered, unless contraindicated.
150 mg twice daily may be considered, unless contraindicated.
Where patients are at are
Where patients a higher risk of
at a higher riskbleeding (HAS-BLED
of bleeding t3),dabigatran
(HAS-BLEDt3), 110
dabigatran 110
IC IC Where patients are at considered,
a higherunless
riskunless
of contraindicated.
bleeding (HAS-BLED t3), dabigatran 110
mg
ICICtwicemg
daily may
twice bemay
daily considered,
be contraindicated.
mg twice daily may be considered, unless contraindicated.
There
There was was however
however an increase
an increase in rate
in the the rate of gastrointestinalbleeding
of gastrointestinal bleeding with
with the
the
There was however an increase in the rate of gastrointestinal bleeding with the
higher dose of dabigatran, despite an overall lower rates of bleeding at other
sites.
IA
IA Antithrombotic agent should be chosen based upon the absolute risks of stroke
and bleeding and the relative risk and benefit for a given patient.
33
6.3.4 INVESTIGATIONAL AGENTS
higher dose of dabigatran, despite an overall lower rates of bleeding at other
sites.
Antithrombotic agent should be chosen based upon the absolute risks of stroke
and bleeding and the relative risk and benefit for a given patient.
6.3.4 INVESTIGATIONAL AGENTS
Several new anticoagulant drugs-broadly in two classes, another oral direct

thrombin inhibitors (e.g. AZD0837) and the oral factor Xa inhibitors (rivaroxaban,
apixaban, edoxaban, betrixaban, YM150, etc.)-are being developed for stroke
prevention in AF.
6.3.5 ANTIPLATELET AGENT ASPIRIN
Aspirin has been perceived to be safer than VKA in AF patients, but recent trials
have shown that VKA are substantially more effective than aspirin for stroke
prevention, with no difference in major bleeding event rates between VKA and
aspirin treated patients.55,68
In seven primary prevention trials, treatment with aspirin was associated with a
non-signicant 19% reduction in the incidence of stroke. There was an absolute
risk reduction of 0.8% per year for primary prevention trials and 2.5% per year for
secondary prevention by using aspirin. When data from all comparisons of
antiplatelet agents and placebo or control groups were included in the meta-
analysis, antiplatelet therapy reduced stroke by 22%.55
The magnitude of stroke reduction from aspirin vs. placebo in the meta-analysis
is broadly similar to that seen when aspirin is given to vascular disease subjects.
Given that AF commonly co-exists with vascular disease, the modest benet
seen for aspirin in AF is likely to be related to its effects on vascular disease.
In the Japan Atrial Fibrillation Stroke Trial,69 patients with lone AF were
randomized to an aspirin group (aspirin at 150 – 200 mg/day) or a placebo
control group. The primary outcomes of cardiovascular death and non fatal
stroke or TIA was 3.1% per year in the aspirin group and was worse than those
in the control group, 2.4% per year, and treatment with aspirin caused a non-
signicant increased risk of major bleeding (1.6%) compared with control (0.4%).
The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study also
showed that VKA (target INR 2 – 3) was superior to aspirin 75 mg daily in
reducing the primary endpoint of fatal or disabling stroke, intracranial
hemorrhage, or thromboembolism by 52%, with no difference in the risk of major
hemorrhage between VKA and aspirin.68
6.3.6 ASPIRIN AND CLOPIDOGREL COMBINATION
In patients with non valvular AF, adjusted dose VKA was found to be superior to
the combination of clopidogrel (75mg daily) plus aspirin (75-100 mg daily) for the
prevention of first occurrence of stroke, non-CNS systemic embolism, myocardial
infarction and vascular death.56
However, clopidogrel (75mg daily) plus aspirin (75-100 mg daily) conferred a

relative risk reduction of 11% compared to aspirin.57
There was an increased risk of major bleeding in patients receiving clopidogrel

plus aspirin compared to patients receiving aspirin alone and was broadly similar
to that seen with VKA.57
Combination therapy with aspirin 75–100 mg plus clopidogrel 75 mg daily, should

B be considered for stroke prevention in patients for whom there is patient refusal
34
to take OAC therapy or a clear contraindication to OAC therapy (e.g. inability to
cope or continue with anticoagulation monitoring), where there is a low risk of
However, infarction
clopidogrel (75mg death.
and vascular daily) 56plus aspirin (75-100 mg daily) conferred a
relative risk reduction of 11% compared to aspirin.57
However, clopidogrel (75mg daily) plus aspirin (75-100 mg daily) conferred a
57
There wasrelative risk reduction
an increased riskofof11% compared
major to aspirin.
bleeding in patients receiving clopidogrel
plus aspirin compared to patients receiving aspirin alone and was broadly similar
There was an57increased risk of major bleeding in patients receiving clopidogrel
to that seen
pluswith VKA.
aspirin compared to patients receiving aspirin alone and was broadly similar
to that seen with VKA.57
Keypoints
Combination therapy with aspirin 75–100 mg plus clopidogrel 75 mg daily, should
IIaB be considered for stroke
Combination prevention
therapy in 75–100
with aspirin patientsmgforplus
whom there 75
clopidogrel is patient
mg daily,refusal
should
IIaB
toIIaB
take OACbe considered
therapy orfora stroke
clear prevention in patients
contraindication for whom
to OAC there(e.g.
therapy is patient refusal
inability to
to take OAC
cope or continue withtherapy or a clear contraindication
anticoagulation to OACthere
monitoring), where therapyis (e.g.
a lowinability
risk ofto
cope or continue with anticoagulation monitoring), where there is a low risk of
57
bleeding. 57
bleeding.
In some patients with onewith
In some patients ‘clinically relevant
one ‘clinically non-major’
relevant riskrisk
non-major’ factor,
factor,e.g.,
e.g.,female
female
IIbC IIbC
patients
IIbC aged <65
patients years
aged <65with
yearsnowith
other risk factors,
no other aspirin
risk factors, aspirinmaymaybebeconsidered
considered
rather than OACthan
rather therapy.
OAC therapy.
6.4 ANTICOAGULATION
6.4 ANTICOAGULATION IN SPECIAL
IN SPECIAL CIRCUMSTANCES
CIRCUMSTANCES
6.4.1 PERIOPERATIVE ANTICOAGULATION
6.4.1 PERIOPERATIVE ANTICOAGULATION
Patients with AF who are anticoagulated will require temporary interruption of
Patients with
VKA AF who are
treatment beforeanticoagulated will require
surgery or an invasive temporary
procedure. interruption
Many surgeons of
require
VKA treatment
an INRbefore surgery
less than 1.5 or or anINR
even invasive procedure.
normalization beforeMany surgeons
undertaking require
surgery. The
an INR lessriskthan 1.5 or signicant
of clinically even INR bleeding,
normalization beforeoutpatients
even among undertaking surgery.minor
undergoing The
procedures,
risk of clinically should be
signicant weighed even
bleeding, against the riskoutpatients
among of stroke andundergoing
thrombo-embolism
minor
in an individual patient before the administration of bridging
procedures, should be weighed against the risk of stroke and thrombo-embolism anticoagulant
therapy. (see Appendix C.1.9, page 80)
in an individual patient before the administration of bridging anticoagulant
therapy. (see
If theAppendix
VKA usedC.1.9, pagewhich
is warfarin, 80) has a half-life of 36 – 42 h, treatment should
be interrupted for about 5 days before surgery (corresponding approximately to
If the VKAveused is warfarin,
half-lives which has a half-life of 36 – 42 h, treatment should
of warfarin),
be interrupted for about 5 days before surgery (corresponding approximately to
Examples
ve half-lives of procedures with a low risk of bleeding,
of warfarin),
Dental Surgery – Restorative Surgery and Extractions
Examples of xprocedures with a low risk of bleeding,
o Anticoagulation can be continued with an INR of less than 3.0 and
x Dental Surgery appropriate
– Restorative Surgery
topical andmeasures
haemostatic Extractions
should be used. There is
no need to discontinue warfarin.
o Anticoagulation can be continued with an INR of less than 3.0 and
appropriate topical haemostatic measures should be used. There is
no need to discontinue warfarin.
x Minor Non-Invasive Surgery (e.g., dilation and curettage [D & C])
o Transient adjustment of the INR to below 1.5 for the perioperative

x Minor Non-Invasive Surgery (e.g., dilation and curettage [D & C])
period is required.
In cases o xTransient adjustment of the(e.g.,
INR should
to below 1.5 for the perioperative
x MajorofSurgery
major surgery,
Minor Non-Invasive consideration
is(Interruption
period(see required.
Surgery dilation
of Anticoagulation be
and given
curettage
Required) to[Dthe
& C])risk of
thromboembolism. CHA2DS2Vasc scoring on page 29)
o Transient adjustment of the INR to below 1.5 for the perioperative
o In mostperiod people without mechanical prosthetic heart valves,
is required.
x Major Surgery (Interruption of Anticoagulation Required)
anticoagulation can be safely discontinued temporarily, without the
xneed
Majorfor heparin
Surgery cover. The
(Interruption decision is made
of Anticoagulation on the basis of the
Required)
o In most people without mechanical prosthetic heart valves,
risk of thrombosis.
anticoagulation
o In most can be safely
people without discontinued
mechanical temporarily,
prosthetic heartwithout the
valves,
need foranticoagulation
heparin cover. canThe decision
be safely is madetemporarily,
discontinued on the basis of the
without the
In patients with AF who do not have mechanical prosthetic heart valves or those
risk of thrombosis.
need for heparin cover. The decision is made on the basis of the
IIaC who are not at high risk risk offor thrombo-embolism who are undergoing surgical or
thrombosis.
Keypoints
diagnostic procedures that carry a risk of bleeding, the interruption of OAC (with sub
In patients with AF who do not have mechanical prosthetic heart valves or those
IIaC therapeuticInanticoagulation
patients with AF for who updotonot48 have
h) should be considered,
mechanical without
prosthetic heart substituting
valves or those
whoIIaCareasnot
IIaC who atarehigh risk for risk
thrombo-embolism
notanticoagulation
at high fortherapy.
thrombo-embolism whowho areare
undergoing
undergoing surgical or
heparin ‘bridging’ (see Appendix C.1.9 on pagesurgical
80). or
diagnostic diagnostic
procedures that carry
procedures thatacarry
risk of bleeding,
a risk the interruption
of bleeding, of of
the interruption OACOAC(with
(with sub
sub
therapeutictherapeutic
anticoagulation for up to
anticoagulation for48up h) should
to 48 be considered,
h) should be considered,without
withoutsubstituting
substituting
In patients with a mechanical prosthetic heart valve or AF at high risk for
IIaC heparin asheparin
‘bridging’ anticoagulation
as ‘bridging’ therapy.
anticoagulation (see (see
therapy. Appendix
AppendixC.1.9 onon
C.1.9 page
page80).
80).
thrombo-embolism who are undergoing surgical or diagnostic procedures,
‘bridging’ Inanticoagulation
patients with therapeutic
with a mechanical prosthetic dosesvalve of either LMWH or
InIIaC
patients with
IIaC a mechanical prosthetic heartheart
valve or or AFAFatathighhigh risk for
risk for
IIaC unfractionated heparin during
thrombo-embolism whotheare temporary
undergoing interruption
surgical or of diagnostic
OAC therapy should
procedures,
thrombo-embolism who are undergoing surgical or
‘bridging’ anticoagulation with therapeutic doses of either LMWH or diagnostic procedures,
be considered.
‘bridging’ unfractionated
anticoagulation heparinwithduringtherapeutic
the35temporarydoses of ofeither
interruption LMWH
OAC therapy should or
unfractionated heparin during the temporary interruption of OAC therapy should
be considered.
Following surgical procedures, resumption of OAC therapy should be considered
need for heparin cover. The decision is made on the basis of the
In patients withriskAF
of who
thrombosis.
do not have mechanical prosthetic heart valves or those
IIaC who are not at high risk for thrombo-embolism who are undergoing surgical or
In patientsprocedures
diagnostic with AF who thatdocarry
not ahave mechanical
risk of prosthetic
bleeding, the heartofvalves
interruption or those
OAC (with sub
IIaC who are not
therapeutic at high risk for
anticoagulation thrombo-embolism
for up to 48 h) should be who are undergoing
considered, surgical or
without substituting
diagnostic
heparin as ‘bridging’ anticoagulation therapy. (see Appendix C.1.9 on page 80). sub
procedures that carry a risk of bleeding, the interruption of OAC (with
therapeutic anticoagulation for up to 48 h) should be considered, without substituting
heparin as ‘bridging’
In patients with a anticoagulation therapy. (see
mechanical prosthetic heartAppendix
valve or C.1.9
AF onat page
high 80).
risk for
IIaC thrombo-embolism who are undergoing surgical or diagnostic procedures,
In patients anticoagulation
‘bridging’ with a mechanical with prosthetic
therapeuticheartdoses
valve orof AF at high
either LMWH risk for
or
IIaC thrombo-embolism
unfractionated heparin whoduring
are the
undergoing
temporarysurgical or diagnostic
interruption procedures,
of OAC therapy should
‘bridging’ anticoagulation with therapeutic doses of either LMWH or
be considered.
unfractionated heparin during the temporary interruption of OAC therapy should
be considered.
Following surgical procedures, resumption of OAC therapy should be considered
IIaB
IIaB at the ‘usual’ maintenance dose (without a loading dose) on the evening of (or
Following surgicalafter)
the next morning procedures,
surgery,resumption
assuming there of OAC therapy should
is adequate be considered
haemostasis.
IIaB at the ‘usual’ maintenance dose (without a loading dose) on the evening of (or
the nextsurgical
When morningprocedures
after) surgery, assuming
require there is
interruption ofadequate
OAC therapyhaemostasis.
for longer than
IIbC
IIbC 48h in high-risk patients, unfractionated heparin or subcutaneous LMWH may be
When surgical
considered. procedures require interruption of OAC therapy for longer than
IIbC 48h in high-risk patients, unfractionated heparin or subcutaneous LMWH may be
considered.
6.4.2 ACUTE STROKE
6.4.2
In allACUTE
Keypoints
IIaC STROKE
patients with AF who have had an acute stroke, any uncontrolled
hypertension should be appropriately managed before antithrombotic therapy is
IIaC
IIaC In all .patients with AF who have had an acute stroke, any uncontrolled
started
hypertension should be appropriately managed before antithrombotic therapy is
IIaC started
Patients. with AF and an acute stroke should have imaging done to exclude
cerebral haemorrhage. In the presence of cerebral infarction, the decision on the
IIaC
IIaC Patients
timing of with AF and anshould
anticoagulation acute be
stroke should
weighed have imaging
between the risk done to exclude
of haemorrhagic
cerebral haemorrhage.
transformation In the
and the risk presence thromboembolism.
of recurrent of cerebral infarction, the decision on the
timing of anticoagulation should be weighed between the risk of haemorrhagic
transformation
x In the and the risk of
absence of recurrent thromboembolism.
haemorrhage, anticoagulation may start 2 weeks
after stroke.
x In the presence of a large infarct, anticoagulation maymay
x In the absence of haemorrhage, anticoagulation start 2 weeks
be delayed after
after stroke.
2 weeks.
x In thex presence of haemorrhage,
In the presence anticoagulation
of a large infarct, anticoagulationshould
may be be withheld
delayed after
2 weeks.
until an appropriate time.
x In the presence of haemorrhage, anticoagulation should be withheld
until an appropriate time.
Patients with AFx and a recent
In the TIAofshould
presence have imaging
a large infarct, done to
anticoagulation exclude
may cerebral
be delayed after
C 2 weeks.
haemorrhage.
Patients with AF and a recent TIA should have imaging done to exclude cerebral
IIaC
IIaC x In the presence of haemorrhage, anticoagulation should be withheld
haemorrhage.
x until an of
In the absence appropriate time.
a haemorrhage, anticoagulation should be started as
soon asx possible.
Patients
In the absence of a haemorrhage, anticoagulation should be started as
with AF and a recent TIA should have imaging done to exclude cerebral
IIaC soon as possible.
haemorrhage.
In patients with AF who sustain ischaemic stroke or systemic embolism during
C treatment In patients
with usual with AF who sustain ischaemic
withstroke
VKA or systemic embolism during
IIbC
IIb C x In intensity anticoagulation
the absence of a haemorrhage, (INR
anticoagulation2.0–3.0), raising
should be startedthe
as
treatment with usual intensity anticoagulation with VKA (INR 2.0–3.0), raising the
intensity of the anticoagulation
soon as possible.to a maximum target INR of 3.0–3.5 may be
intensity of the anticoagulation to a maximum target INR of 3.0–3.5 may be
considered, rather than
considered, adding
rather an antiplatelet
than adding agent.
an antiplatelet agent.
In patients with AF who sustain ischaemic stroke or systemic embolism during
IIb C treatment with usual intensity anticoagulation with VKA (INR 2.0–3.0), raising the
6.4.3 Anticoagulant and Antiplatelet
6.4.3 Anticoagulant Therapy
and Antiplatelet UseUse
Therapy in Patients With
in Patients WithAtrial
Atrial
intensity of the anticoagulation to a maximum target INR of 3.0–3.5 may be
Fibrillation
Fibrillation UndergoingUndergoing Percutaneous Coronary Intervention
considered, ratherPercutaneous Coronary
than adding an antiplatelet Intervention
agent.
There
There is 6.4.3
a lack is of
a lack of published
published evidence on what is the optimalmanagement
management
Anticoagulant andevidence onTherapy
Antiplatelet what is
Usethe optimal
in Patients With Atrial
strategy in anticoagulated patients with nonvalvular atrial fibrillation (AF) who
strategy inFibrillation
anticoagulated patients
Undergoing with nonvalvular
Percutaneous Coronary atrial fibrillation (AF) who
Intervention
undergo percutaneous coronary intervention (PCI) and, hence, need antiplatelet
undergo percutaneous
therapy. coronary intervention (PCI) and, hence, need antiplatelet
therapy. There is a lack of published evidence on what is the optimal management
strategyoninconsensus,
Based anticoagulated patients strategy
the post-PCI with nonvalvular
should beatrial fibrillation
tailored to the (AF) who
individual
undergo
Based on patient
consensus,
andpercutaneous
the
their of coronary
riskpost-PCI intervention
strategy
thromboembolism and(PCI)
should beand,
stent hence,toneed
tailored
thrombosis the antiplatelet
individual
weighed against
therapy
their risk. risk
of bleeding while receiving triple
patient and their of thromboembolism andtherapy (see Table 13)
stent thrombosis weighed against
their risk of bleeding
Based while receiving
on consensus, triple therapy
the post-PCI strategy (see
shouldTable 13) to the individual
be tailored
Following elective PCI in patients with AF with stable coronary artery disease,
IIaC patient and their risk of thromboembolism and stent thrombosis weighed against
BMS should be considered, and drug-eluting stents avoided or strictly limited to
Following their
Keypoints those
risk ofPCI
elective bleeding
clinical and/or
while receiving
in patients with AF
anatomical
triple
withtherapy
situations stable(see Table 13)artery disease,
coronary
(e.g. long lesions, small vessels,
C
BMS should be considered,
diabetes, etc.), where and drug-eluting
a signicant benetstents avoided
is expected whenor strictly limited
compared to
with BMS.
those Following elective PCI in patients with AF with stable coronary artery disease,
IIaC clinical and/or anatomical situations (e.g. long lesions, small vessels,
IIaC BMS should be considered, and drug-eluting stents avoided or strictly limited to
diabetes, etc.), where
Following a signicant
elective benet
PCI, triple is expected
therapy when compared
(VKA, aspirin, clopidogrel) with
those clinical and/or anatomical situations (e.g. long lesions, small vessels,
BMS.
should be
IIaC considered in the short term, followed by more long-term therapy (up to 1 year)
diabetes, etc.), where a signicant benet is expected when compared with BMS.
Following with VKA plus
elective clopidogrel
PCI, 75 mg daily
triple therapy (or, alternatively,
(VKA, aspirin 75–100
aspirin, clopidogrel) mg daily).
should be
C considered in the short
Following term,
elective PCI,followed 36 more
by
triple therapy long-term
(VKA, aspirin,therapy (up to
clopidogrel) 1 year)
should be
IIaC Following elective PCI, clopidogrel should be considered in combination with
with VKA plus
VKA clopidogrel
plus aspirin 75
considered
for mg
in the short daily
term,
a minimum (or,
of alternatively,
followed
1 month after aspirin 75–100
by more long-term therapy
implantation of amg
(up to daily).
1 year)
BMS, but
patient and their risk of thromboembolism and stent thrombosis weighed against
Following their
elective
risk ofPCI in patients
bleeding with AF
while receiving with
triple stable
therapy coronary
(see Table 13)artery disease,
IIaC
BMS should be considered, and drug-eluting stents avoided or strictly limited to
those
IIaC
clinical and/or
Following anatomical
elective situations
PCI in patients with AF (e.g.
withlong
stablelesions,
coronarysmall
artery vessels,
disease,
diabetes, BMS
etc.),should
wherebe considered, benet
a signicant and drug-eluting
is expected stents avoided
when or strictly
compared limited
with BMS.to
those clinical and/or anatomical situations (e.g. long lesions, small vessels,
Following diabetes,
electiveetc.),
PCI, where a signicant benet is expected when compared with BMS.
triple therapy (VKA, aspirin, clopidogrel) should be
IIaC considered in the short term,
Following elective PCI,followed by more
triple therapy long-term
(VKA, aspirin,therapy (up to
clopidogrel) 1 year)
should be
IIaC
with
IIaCVKA considered
plus clopidogrel 75 mg
in the short daily
term, (or, alternatively,
followed aspirintherapy
by more long-term 75–100(upmg
to 1daily).
year)
with VKA plus clopidogrel 75 mg daily (or, alternatively, aspirin 75–100 mg daily).
IIaC Following elective PCI, clopidogrel should be considered in combination with
IIaC plusFollowing
VKA
IIaC elective
aspirin for PCI, clopidogrel
a minimum shouldafter
of 1 month be considered
implantationin combination
of a BMS, withbut
longer withVKA plus aspirin forstent
a drug-eluting a minimum of 3
(at least 1 months
month after
for implantation of a BMS,stent
a sirolimus-eluting but
longer with a drug-eluting stent (at least 3 months for a sirolimus-eluting stent
and at least 6 months for a paclitaxel-eluting stent); following which VKA and
and at least 6 months for a paclitaxel-eluting stent); following which VKA and
clopidogrel 75 mg daily
clopidogrel 75 mg(or, alternatively,
daily aspirin
(or, alternatively, 75–100
aspirin 75–100mgmg
daily).
daily).
6.4.4 NON-ST ELEVATION

6.4.4 NON-ST MYOCARDIAL
ELEVATION INFARCTION
MYOCARDIAL INFARCTION
In patientsIn with
patients with non-ST
non-ST elevation
elevation myocardial
myocardial infarction,
infarction, dual
dual antiplatelet therapy
antiplatelet therapy
with aspirin plus clopidogrel is recommended, but in AF patients at moderate to
high risk of stroke, OAC should also be given.
In the acute setting, patients are often given aspirin, clopidogrel, UFH, or LMWH
(e.g. enoxaparin) or bivalirudin and/or a glycoprotein IIb/IIIa inhibitor (GPI). Drug-
eluting stents should be limited to clinical situations, as described above (see
Table 13). An uninterrupted strategy of OAC is preferred, and radial access
should be used as the rst choice.
For medium to long-term management, triple therapy (VKA, aspirin, and

clopidogrel) should be used in the initial period (3 – 6 months), or for longer in
selected patients at low bleeding risk. In patients with a high risk of
cardiovascular thrombotic complications [e.g. high Global Registry of Acute
Coronary Events (GRACE) or TIMI risk score], long-term therapy with VKA may
be combined with clopidogrel 75 mg daily (or, alternatively, aspirin 75 – 100 mg
daily).
<<Table 13>>
Table 13: Antithrombotic strategies following coronary artery stenting in patients with AF at moderate to high
thrombo-embolic risk (in whom oral anticoagulation therapy is required)
Haemorrhagic risk Clinical Stent implanted Anticoagulation regimen

Following an ACS with or without PCI
setting
in patients with AF, triple therapy (VKA,
IIaC aspirin, clopidogrel)
Low or intermediate (e.g should
Elective be considered
Bare-metal in the short term
1 month: triple(3–6
therapymonths),
of VKA (INRor
longer
HAS-BLEDin score
selected
0-2) patients at low bleeding risk, followed byaspirin
2.0-2.5) + long-term therapy
75-100mg/day
+clopidogrel 75 mg/day
Lifelong: VKA (INR 2.0-3.0) alone
Elective Drug-eluting 3 (-olimusa group) to 6 (paclitaxel)
In anticoagulated patients at very high risk of thrombo-embolism, uninterrupted
months: triple therapy of VKA (INR
IIaC 2.0-2.5) + aspirin 75-100mg/day
therapy with VKA as the preferred strategy and radial access used as the rst
choice even during therapeutic anticoagulation (INR 2–3). th
Up to 12 month: combination of
VKA (INR 2.0-2.5) + clopidogrel
75/dayb
When VKA is given in combination with clopidogrel or low-dose aspirin, careful
IIbC (or aspirin 100m/day)
regulation of the anticoagulation dose intensity may be considered,
Lifelong: with alone
VKA (INR 2.0-3.0) an INR
range of 2.0–2.5. ACS Bare-metal/drug- 6 months: triple therapy of VKA (INR
eluting 2.0-2.5) + aspirin 75-100mg/day
IIbC Following revascularization surgery in patients with AF,
Up to 12th VKA plus a single
month: combination of
VKA (INR but
antiplatelet drug may be considered in the initial 12 months, 2.0-2.5)
this+ clopidogrel
strategy has
75/dayb
not been evaluated thoroughly and is associated with (or
anaspirin
increased
100m/day)risk of
bleeding. Lifelong: VKA (INR 2.0-3.0) alone
High Elective Bare-metalc 2-4 weeks: triple therapy of VKA
(e.g, HAS-BLED score (INR 2.0-2.5) + aspirin 75-
In>3)
patients with stable vascular disease (e.g. >1 year, 100mg/day
with no acute events),
+clopidogrel VKA
75 mg/day
IIbC monotherapy may be considered, and concomitant Lifelong: antiplatelet
VKA (INR therapy should
2.0-3.0) alone
not be prescribed in theACS
absence of Bare-metalc 4 weeks: triple therapy
a subsequent cardiovascular event.of VKA (INR
2.0-2.5) + aspirin 75-100mg/day
(or aspirin 100m/day)
37 INR = international normalized ratio; VKA = vitamin

ACS = acute coronary syndrome; AF = atrial fibrillation;
K antagonist.
Gastric protection with a proton pump inhibitor (PPI) should be considered where necessary.
with aspirin plus clopidogrel is recommended, but in AFVKA
Lifelong: patients at moderate
(INR 2.0-3.0) alone to
High high risk of stroke,
ElectiveOAC should also be given.
Bare-metalc 2-4 weeks: triple therapy of VKA
(e.g, HAS-BLED score (INR 2.0-2.5) + aspirin 75-
>3) 100mg/day +clopidogrel 75 mg/day
In the acute setting, patients are often given aspirin, clopidogrel,
Lifelong: UFH, or
VKA (INR 2.0-3.0) LMWH
alone
(e.g. enoxaparin)
ACS or bivalirudin and/or a glycoprotein
Bare-metalc IIb/IIIa
4 weeks: tripleinhibitor
therapy of(GPI). Drug-
VKA (INR
eluting stents should be limited to clinical situations,
2.0-2.5) as described
+ aspirin above (see
75-100mg/day
Table 13). An uninterrupted strategy of OAC is preferred, and radial access
should be used as the rst choice. (or aspirin 100m/day)
For medium to long-term management, triple therapy (VKA, aspirin, and
ACS = acute coronary syndrome; AF = atrial fibrillation; INR = international normalized ratio; VKA = vitamin
K antagonist.
clopidogrel) should be used in the initial period (3 – 6 months), or for longer in
selected
Gastric protection patients
with a proton pumpatinhibitor
low (PPI)
bleeding risk.
should be In patients
considered with a high risk of
where necessary.
a
cardiovascular
Sirolimus, everolimus, thrombotic complications [e.g. high Global Registry of Acute
and tacrolimus.
b
CombinationCoronary
of VKA (INR Events (GRACE)100
2.0–3.0)+aspirin or TIMI risk(with
mg/day score],
PPI, long-term
if indicated)therapy with VKA as
may be considered may
an
alternative. be combined with clopidogrel 75 mg daily (or, alternatively, aspirin 75 – 100 mg
c
Drug-eluting stents should be avoided as far as possible, but, if used, consideration of more prolonged (3–6
daily).
months) triple antithrombotic therapy is necessary.
54
Adapted from Lip et al.
<<Table 13>>
Keypoints
Following an ACS with or without PCI in patients with AF, triple therapy (VKA,
IIaC
IIaC aspirin, clopidogrel) should be considered in the short term (3–6 months), or
longer in selected patients at low bleeding risk, followed by long-term therapy
In anticoagulated patients at very high risk of thrombo-embolism, uninterrupted

IIaC
IIaC
therapy with VKA as the preferred strategy and radial access used as the rst
choice even during therapeutic anticoagulation (INR 2–3).
IIbC When VKA is given in combination with clopidogrel or low-dose aspirin, careful
IIbC
regulation of the anticoagulation dose intensity may be considered, with an INR
range of 2.0–2.5.
IIbC
IIbC Following revascularization surgery in patients with AF, VKA plus a single
antiplatelet drug may be considered in the initial 12 months, but this strategy has
not been evaluated thoroughly and is associated with an increased risk of
bleeding.
In patients with stable vascular disease (e.g. >1 year, with no acute events), VKA
IIbC
IIbC monotherapy may be considered, and concomitant antiplatelet therapy should
not be prescribed in the absence of a subsequent cardiovascular event.
6.4.5
6.4.5 CARDIOVERSION
CARDIOVERSION
Conversion
Conversion of of AF
AF to to 70sinus
sinus rhythm
rhythm results
results in in transient
transient mechanical
mechanical dysfunction
dysfunction of of
the
the LA and
LA 6.4.5 LAA
and CARDIOVERSION
LAA 70 ("stunning"),
("stunning"), which can can occur
occur after
after spontaneous,
48,71 71-73 which spontaneous,
pharmacological,
pharmacological, 48,71 or electrical71-73 conversion of AF. Thrombus may form
during Conversionofofor AFelectrical
to sinus rhythmconversion of AF.mechanical
transient
results in after Thrombusdysfunction
may form of
during the
thetheperiod
period
LA and of stunning
stunning and
and is is expelled
LAA70 ("stunning"), expelled
which after
the return
can the return
occur
of mechanical
afterof spontaneous,
mechanical
function, explaining
function, explaining the clustering
the clustering of thromboembolic
of thromboembolic events during the first 10 d
pharmacological,
74,75
48,71
or electrical71-73
conversionevents
of AF. during
Thrombusthe first
may 10 formd
after
after cardioversion.
cardioversion. periodRecovery
during the 74,75 of stunningof
Recovery ofandmechanical
is expelled function
mechanical function
after the may
may be
return be delayed,
delayed,
of mechanical
76,46,87
depending partially
dependingfunction, on the
partiallyexplaining duration of AF
the clustering
on the duration before
of AFofbefore conversion.
thromboembolic
conversion. 76,46,87
events during the first 10 d
after cardioversion.74,75 Recovery of mechanical function may be delayed,
76,46,87 77,78
The
The risk
risk of thromboembolism
ofdepending after
partially on the
thromboembolism cardioversion
duration
after is
of AF before
cardioversion between 1%
between
is conversion. 1% andand 5%
5%77,78 and
and
is reduced
is reduced when
when anticoagulation
anticoagulation (INR
(INR 2.0
2.0 to
to 3.0)
3.0) is
is given
given for
for 4
4 wk
wk before
before and
77,78and
The
after conversion risk of
79,80 thromboembolism
(see Figure
conversion79,80 (see Figure 9).
9). after cardioversion is between 1% and 5% and
after is reduced when anticoagulation (INR 2.0 to 3.0) is given for 4 wk before and
79,80
after conversion (see Figure 9).
Keypoints
For patients
For patients with
with AF
AF oror AFL
AFL ofof 48-h
48-h duration
duration or
or longer,
longer, or or when
when the
the duration
duration of
of
AF
AF or AFL is
For unknown,
patients withanticoagulation
AF or AFL of 48-h
or AFL is unknown, anticoagulation (INR 2.0
2.0 to
duration
(INR or 3.0)
to is
longer,
3.0) recommended
is or for
for at
when the duration
recommended of
at
IB
IB
least
least 44 weeks
AF orprior
weeks AFL to
prior is and
to 4
4 weeks
unknown,
and after
after cardioversion,
anticoagulation
weeks
64
(INR 2.0 toregardless
cardioversion, of
of the
the method
3.0) is recommended
regardless for at
method
used
used toto restore
least 4sinus
restore weeksrhythm.
sinus prior to 64
rhythm. and 4 weeks after cardioversion, regardless of the method
used to restore sinus rhythm.64
For
For patients
patients with AF requiring immediate/emergency cardioversion because of
For with AF with
patients requiring immediate/emergency
AF requiring immediate/emergency cardioversion
cardioversionbecause
because of of
haemodynamic
ICIC
haemodynamic instability,
instability, heparin (i.v.
(i.v. UFH
heparinheparin UFH bolus followed
bolusbolus
followed by infusion,
by by
infusion, or weight-
haemodynamic instability, (i.v. UFH followed infusion,ororweight-
weight-
adjusted therapeutic
adjusted therapeutic dose LMWH)
dose LMWH)
adjusted therapeutic is recommended.
is recommended.
dose LMWH) is recommended.
After
After immediate/emergency cardioversion
After immediate/emergency
immediate/emergency in
in patients
cardioversion
cardioversion with
in patients
patients AF
withwith
AFAF of 48
4848hour
of of hourduration
hour duration
duration
orI IB
or longer, or
longer,
B or when
orlonger,
when or the duration
thewhen of
of AF
the duration
duration is
AF of unknown,
is AF OAC
is unknown,
unknown, OACOAC therapy is
therapy
therapy recommended
is is recommended
recommended
for at least 4 weeks, similar to patients undergoing elective cardioversion.6464
for at
for at least
least 4
4 weeks,
weeks, similar
similar to
to patients
patients undergoing
undergoing elective
elective cardioversion.
cardioversion. 64
For Forwith
patients AF with
patients AF duration
duration that is that38is clearly <48 h and no thrombo-embolic risk
risk
For
IIbCpatients with i.v.
factors, AF duration
heparin orthat is clearly
clearly
weight-
<48 h
h and
and no
no thrombo-embolic
<48 therapeutic
adjusted thrombo-embolic
dose LMWH mayrisk be
factors, i.v. heparin or weight- adjusted therapeutic dose LMWH may be
For patients with AF requiring immediate/emergency cardioversion because of
IC haemodynamic instability, heparin (i.v. UFH bolus followed by infusion, or weight-
adjusted therapeutic dose LMWH) is recommended.
After immediate/emergency cardioversion in patients with AF of 48 hour duration

IB or longer, or when the duration of AF is unknown, OAC therapy is recommended
for at least 4 weeks, similar to patients undergoing elective cardioversion. 64
For patients with AF duration that is clearly <48 h and no thrombo-embolic risk
IIbC
IIbC factors, i.v. heparin or weight- adjusted therapeutic dose LMWH may be
considered peri-cardioversion, without the need for post-cardioversion oral
anticoagulation.
It is important to stress that in following cardioversion of all patients at high risk of

AF recurrence or with stroke risk factors, consideration should be given towards
long-term anticoagulation, as thromboembolism may occur during asymptomatic
recurrence of AF.
For patients with AF <48 h and at high risk of stroke, i.v. heparin or weight-
IIB
B
adjusted therapeutic dose LMWH is recommended peri-cardioversion, followed
by OAC therapy with a VKA (INR 2.0–3.0) long term.49,55,64
In patients at high risk of stroke, OAC therapy with a VKA (INR 2.0–3.0) is
IIB
B
recommended to be continued long-term.49,55,64
<<Figure 9>>
Figure 9: Cardioversion of haemodynamically stable AF, the role of TOE-guided cardioversion, and
subsequent anticoagulation strategy. AF = atrial fibrillation; DCC = direct current cardioversion; LA = left
atrium; LAA = left atrial appendage; OAC = oral anticoagulant; SR = sinus rhythm; TOE = transoesophageal
echocardiography.
39
As an alternative to anticoagulation prior to cardioversion of AF or AFL, it is
reasonable to perform TOE in search of thrombus.13
x For As
patients with noto identifiable
an alternative thrombus,
anticoagulation cardioversion
prior to cardioversion is or
of AF reasonable
AFL, it is
IBIB
immediately
reasonableafter anticoagulation.
to perform TOE in search of thrombus.13
x Thereafter,
IIaB
IIaB
x For continuation of identifiable
patients with no oral anticoagulation (INR 2.0 istoreasonable
thrombus, cardioversion 3.0) is
immediately
reasonable after
for at least 4 anticoagulation.
weeks, as for elective cardioversion.
IIaB x Thereafter, continuation of oral anticoagulation (INR 2.0 to 3.0) is

x For patients in whom thrombus is identified, oral anticoagulation (INR 2.0 to
IIaB reasonable for at least 4 weeks, as for elective cardioversion.
3.0) is reasonable for at least 4 weeks before and 4 weeks after
IIaB restoration
x For of sinusinrhythm,
patients and longer
whom thrombus anticoagulation
is identified, may be appropriate
oral anticoagulation (INR 2.0 to
IIaB
after apparently successful
3.0) is reasonable for atcardioversion,
least 4 weeks beforebecause and the
4 weeksrisk after
of
thromboembolism
restorationoften remains
of sinus rhythm,elevated
and longerinanticoagulation
such cases. may be appropriate
after apparently successful cardioversion, because the risk of
thromboembolism
For patients undergoing often remains
a TOE-guided elevated
strategy in suchthrombus
in whom cases. is identied,
VKA (INR 2.0–3.0) is recommended for at least 4 weeks, followed by a repeat
For patients undergoing a
ICIC to ensure thrombus resolution. TOE-guided strategy in whom thrombus is identied,
TOE VKA (INR 2.0–3.0) is recommended for at least 4 weeks, followed by a repeat
TOE to ensure thrombus resolution.
If thrombus resolution is evident on repeat TOE, cardioversion should be
performed,If and OAC should
thrombus be isconsidered
resolution evident onfor 4 weeks
repeat TOE,orcardioversion
lifelong (if risk factors
should be
IIaC
IIaC
are present).
performed, and OAC should be considered for 4 weeks or lifelong (if risk factors
are present).
If thrombus remains on repeat TOE, an alternative strategy (e.g. rate control)
If thrombus remains on repeat TOE, an alternative strategy (e.g. rate control)
mayIIbCbe considered.
IIbC may be considered.
Thismay
This strategy be useful
strategy may be to allow
useful to early cardioversion
allow early of patients
cardioversion of patientswith
withAF
AF !! 48
48
hours or where a minimal
hours or period period
where a minimal of anticoagulation is preferred.
of anticoagulation is preferred.
6.5 NON-PHARMACOLOGICAL
6.5 NON-PHARMACOLOGICAL METHODS
METHODS TO PREVENT
TO PREVENT STROKE
STROKE
The left atrial appendage (LAA) is considered the main site of atrial
The left thrombogenesis
atrial appendage (LAA)occlusion
and thus, is considered
of the LAA the orice
main may
site reduce
of atrial
the
thrombogenesis and ofthus,
development occlusion
atrial thrombi of the
and stroke LAA with
in patients orice
AF may reduce the
development of atrial thrombi and stroke in patients with AF
The PROTECT AF trial81 randomized 707 eligible patients to percutaneous
closure of 81 using a WATCHMAN device and subsequent discontinuation
The PROTECT AFthetrial
LAA randomized 707 eligible patients to percutaneous
closure ofofthe
warfarin (intervention,
LAA using n = 463), ordevice
a WATCHMAN to VKA and
treatment (INR range
subsequent 2 – 3; control,
discontinuation
n = 244). The primary efficacy event rate (a composite endpoint of stroke,
of warfarin (intervention, n = 463), or to VKA treatment (INR range 2 – 3; control,
cardiovascular death, and systemic embolism) of the WATCHMAN device was
n = 244).considered
The primary efficacy
non-inferior event
to that rateThere
of VKA. (a composite
was a higherendpoint of stroke,
rate of adverse safety
cardiovascular
eventsdeath,
in theand systemicgroup
intervention embolism)
than inofthe
thecontrol
WATCHMAN
group, due device was
mainly to
consideredperiprocedural
non-inferior complications.
to that of VKA. There was a higher rate of adverse safety
events in the intervention group than in the control group, due mainly to
periprocedural complications.
6.6 RISK OF LONG-TERM ANTICOACULATION
6.6.1. ASSESSMENT OF RISK OF BLEEDING
An assessment of bleeding risk should be part of the clinical assessment of

patients before starting anticoagulation therapy.
In order to provide adequate thromboprophylaxis with minimal risk of bleeding,

current clinical practice aims for a target INR of between 2.0 and 3.0; INRs of
more than 3.0 are associated with increases in bleeding and INRs of less than
2.0 are associated with increases in stroke risk.
The annual risks of intracranial haemorrhage increased from 0.1% in control to
0.3% in VKA groups, which represents 40 an excess of two intracranial bleeds per
annum per 1,000 patients treated.
6.6 RISK OF LONG-TERM ANTICOACULATION
6.6.1. ASSESSMENT OF RISK OF BLEEDING
An assessment of bleeding risk should be part of the clinical assessment of

patients before starting anticoagulation therapy.
In order to provide adequate thromboprophylaxis with minimal risk of bleeding,

current clinical practice aims for a target INR of between 2.0 and 3.0; INRs of
more than 3.0 are associated with increases in bleeding and INRs of less than
2.0 are associated with increases in stroke risk.
The annual risks of intracranial haemorrhage increased from 0.1% in control to
0.3% in VKA groups, which represents an excess of two intracranial bleeds per
annum per 1,000 patients treated.
Even low-dose aspirin increases the risk of major haemorrhage by two-fold,

especially in the setting of uncontrolled hypertension.
Controlling and monitoring of hypertension and other associated co morbidities is

extremely important in minimizing the risk of bleeding in patients on prophylactic
OAC.
The fear of falls may be overstated, as a patient may need to fall 300 times per
year for the risk of intracranial haemorrhage to outweigh the benet of OAC in
stroke prevention.
While these factors are often cited as reasons for non-prescription of VKA in the
elderly, the absolute benefit is likely to be greatest in this same group in view of
their high risk.68
6.6.2 RISK SCORE FOR BLEEDING
The bleeding risk score HAS-BLED was formulated by incorporating risk factors
from a derivation cohort of a large population database of the prospective Euro
Heart Survey on AF.82 The clinical characteristic comprising the HAS-BLED
bleeding risk score is shown in Table 14.
It is reasonable to use the HAS-BLED score to assess bleeding risk in AF

patients, whereby a score of 3 indicates ‘high risk’, and some caution and
regular review of the patient is needed following the initiation of antithrombotic
therapy, whether with VKA or aspirin.
A schema such as HAS-BLED is a user-friendly method of predicting bleeding

risk and is easy to remember.
41
Table 14 : Clinical characteristics comprising the HAS-BLED bleeding risk score
Table 14 : Clinical characteristics comprising the HAS-BLED bleeding risk score
Letter Clinical characteristica Points awarded

H Hypertension 1
Abnormal renal and liver
A 1 or 2
function (1 point each)
S Stroke 1
B Bleeding 1
L Labile INRS 1
E Elderly (e.g. age >65 years) 1
D Drugs or alcohol (1 point each) 1 or 2
Maximum 9 points
a’
Hypertension’ is defined as systolic blood pressure .160 mmHg. ‘Abnormal kidney function’ is defined
as the presence of chronic dialysis or renal transplantation or serum creatinine 200 mmol/L. ‘Abnormal
liver function’ is defined as chronic hepatic disease (e.g. cirrhosis) or biochemical evidence of significant
hepatic derangement (e.g. bilirubin .2 x upper limit of normal, in association with aspartate
aminotransferase/alanine
a’
aminotransferase/alkaline
Hypertension’
phosphatase .3 isx defined
upper as limitsystolic
normal,blood pressure
etc.). .160 refers
‘Bleeding’ mmHg.to‘Abnormal
previous kidney function’
bleeding historyis defined
and/or
as the presence
predisposition to of chronic e.g.
bleeding, dialysis or renal
bleeding transplantation
diathesis, anaemia, or etc.
serum creatinine
‘Labile refersmmol/L.
INRs’200 ‘Abnormal
to unstable/high
liver function’
INRs or poor is defined
time as chronic range
in therapeutic hepatic(e.g.<60%).
disease (e.g. cirrhosis) or use
Drugs/alcohol biochemical
refers toevidence of significant
concomitant use of
hepaticsuch
drugs, derangement
as antiplatelet(e.g. bilirubin
agents, .2 x upper
non-steroidal limit of normal,
anti-inflammatory in orassociation
drugs, with etc.
alcohol abuse, aspartate
INR =
aminotransferase/alanine
international normalized ratio. aminotransferase/alkaline
phosphatase
Adapted .3 x upper
from Pisters et al. limit normal, etc.). ‘Bleeding’ refers to previous bleeding history and/or
82
predisposition to bleeding, e.g. bleeding diathesis, anaemia, etc. ‘Labile INRs’ refers to unstable/high
INRs or poor time in therapeutic range (e.g.<60%). Drugs/alcohol use refers to concomitant use of
drugs, such<<Table
as antiplatelet
14>>agents, non-steroidal anti-inflammatory drugs, or alcohol abuse, etc. INR =
Keypoints
international normalized ratio.
82
Adapted from Pisters et al.
IIaA
IIaA Assessment of the risk of bleeding should be considered when prescribing
antithrombotic therapy (whether with VKA or aspirin), and the bleeding risk with
aspirin should be considered as being similar to VKA, especially in the
elderly.68,82,83
IIaB The HAS-BLED score [hypertension, abnormal renal/liver function, stroke,

IIaB
bleeding history or predisposition, labile INR, elderly (>65), drugs/alcohol
concomitantly] should be considered as a calculation to assess bleeding risk,
whereby a score of 3 indicates ‘high risk’ and some caution and regular review
is needed, following the initiation of antithrombotic therapy, whether with OAC or
aspirin.82
7 MANAGEMENT – LONGTERM RATE CONTROL
7.1 PHARMACOLOGICAL RATE CONTROL
Criteria for rate control vary with patient age but usually involve achieving
ventricular rates
x 60 - 80 beats per minute at rest and
x 90 – 115 beats per minute during moderate exercise.23
However, maintaining lenient control of heart rate (a resting rate of less than 100
beats per minute) is easier to achieve and is comparable to strict control (a
resting heart rate of 80 beats per minute
42 and a heart rate during moderate
exercise of less than 110 beats per minute) on long-term composite outcomes.84
7.1 PHARMACOLOGICAL RATE CONTROL
ventricular rates
x 60 - 80 beats per minute at rest and
x 90 – 115 beats per minute during moderate exercise.23
However, maintaining lenient control of heart rate (a resting rate of less than 100
beats per minute) is easier to achieve and is comparable to strict control (a
resting heart rate of 80 beats per minute and a heart rate during moderate
exercise of less than 110 beats per minute) on long-term composite outcomes.84
For patients without severe symptoms due to high ventricular rate, a lenient rate
control therapy approach is reasonable (See Figure 10).
<<Figure 10>>
Drugs commonly used are ß-blockers, non-dihydropyridine calcium channel

antagonists, and digitalis. Acute treatment is described in Section 5.1.1.
7 MANAGEMENT
Combinations – LONGTERM
of drugs RATE CONTROL
may be necessary. Dronedarone may also effectively
reduce heart rate during AF recurrences. Amiodarone may be suitable for some
7.1 PHARMACOLOGICAL
patients RATErate
with otherwise refractory CONTROL
control. The combination of a
ß-blocker and digitalis may be benecial in patients with heart failure.
ventricular rates
When a strict rate control policy is adopted (resting heart rate < 80 bpm and a
x 60rate
target heart - 80 of
beats
<110perbpm
minute at rest
during and exercise) a 24 h Holter monitor
moderate
should xbe 90 – 115 beats
performed per minute
to assess pausesduring moderate exercise.23
and bradycardia.
However,
Selection of maintaining lenient control
the most effective of heart rate
and appropriate (a restingagent,
rate-control rate oforless than 100
combination
beats per minute)
of agents, is easier
is vital. Table to achieve
15 lists and treatments
rate-control is comparable to strict
in order control (a
of preference,
resting heart
taking into rate ofother
account 80 beats per minute
conditions that mayandbea present.
heart rate during
Figure 11, moderate
page 47
84
exercise
provides of anless than 110
algorithm on beats
how to permake
minute)
theondrug
long-term
choicecomposite
and Tableoutcomes.
16 list the
For patients
drugs without
and their dosessevere
for ratesymptoms
control. due to high ventricular rate, a lenient rate
control therapy approach is reasonable (See Figure 10).
<<Table 15>> level of heart rate control.
Figure 10:Optimal
<<Figure 10>>
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European
<<Table 16>>
heart Journal 2010; doi:10.1093/eurheartj/ehq278)
Drugs commonly used are ß-blockers, non-dihydropyridine calcium channel

antagonists, and digitalis. Acute treatment is described in Section 5.1.1.
Combinations of drugs may be necessary. Dronedarone may also effectively

reduce heart rate during AF recurrences. Amiodarone may be suitable for some
patients with otherwise refractory rate control. The combination of a
ß-blocker and digitalis may be benecial in patients with heart failure.
When a strict rate control policy is adopted (resting heart rate < 80 bpm and a
target heart rate of <110 bpm during moderate exercise) a 24 h Holter monitor
should be performed to assess pauses and bradycardia.
Selection of the most effective and appropriate rate-control agent, or combination

of agents, is vital. Table 15 lists rate-control treatments in order of preference,
taking into account other conditions that may be present. Figure 11, page 47
provides an algorithm on how to make the drug choice and Table 16 list the
drugs and their doses for rate control.
<<Table 15>>
<<Table 16>>
43
Table 15: Choice of a rate-control agent
Co morbidity First-line Second-line Less effective or

desirable
No heart disease Beta-blockers* Digoxin‡
OR (can be rst-line in
Non-dihydropyridine people unlikely to be
Calcium channel active)
blockers†
Hypertension Beta-blockers* Digoxin‡

OR
Non-dihydropyridine
Calcium channel
blockers†
Ischaemic heart Beta-blockers* First line agent plus Ablation + pacing
disease Non-dihydropyridine
Calcium-channel
blockers†
OR
Digoxin‡
Congestive heart Digoxin in overt heart Beta-blockers* Amiodarone

failure failure (excluding carvedilol,
bisoprolol
Carvedilol or bisoprolol and metoprolol) Ablation and pacing
or metoprolol OR should be considered
in stable heart failure Diltiazem
Chronic obstructive Non-dihydropyridine First line agent plus Digoxin‡

pulmonary disease Calcium channel beta-blockers
blockers† (if there is no
reversible
bronchospasm.
* excluding sotalol
† diltiazem or verapamil
‡ as monotherapy (can be used in combination with other rate-control agents)
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal
44
Table 16: Oral pharmacological agents for rate control in people with atrial fibrillation/atrial flutter
Drug Oral Onset Commonly used Adverse effects Comments

loading of action oral maintenance
dose doses
Beta-blockers
Atenolol N/A 2 to 3 hr 25 to 50 mg Hypotension, In people with
heart block, heart failure,
Carvedilol N/A 60 to 90 min 6.25 to 25 mg bd bradycardia, lower doses may
asthma, heart failure be advisable
Metoprolol N/A 4 to 6 hr 23.75 to 200 mg/day *
(negative inotropic
Nadolol N/A 3 to 4 hr 20 to 80 mg/day effect)
Propanolol N/A 60 to 90 min 80 to 240 mg/day
Calcium channel blockers

Diltiazem N/A 1 to 4 hr 120 to 360 mg/day Hypotension, In people with
heart failure lower doses may
be advisable
Verapamil N/A 1 to 2 hr 120 to 360 mg/day Hypotension, In people with
heart failure, lower doses may
digoxin be advisable
interaction (negative
inotropic effect)
Other
Digoxin 0.5 to 1.0 2 hr 0.0625 to 0.375 Digoxin toxicity, First-line therapy
mg mg/day heart block, only for people
bradycardia unlikely to be active
(eg, older people or
infirm) and for
people with heart
failure.
Less effective in
hyperadrenergic
states
Amiodarone 400 to 800 1 to 3 wk 200 mg/day Photosensitivity Although there
mg/day and other skin is fairly good
for 1 week reactions, evidence of
pulmonary efficacy, this is
toxicity, an agent of last
polyneuropathy, resort in this
gastrointestinal indication, due
upset, to its long-term
bradycardia, toxicity
hepatic toxicity,
thyroid
dysfunction,
torsades de
pointes (rare)
N/A = Not applicable

Adapted from: Fuster V, Ryden LE, Asinger RW, et al.134
Keypoints
Rate control using pharmacological agents (ȕ-blockers, non-dihydropyridine

IB
IB calcium channel antagonists, digitalis, or a combination thereof) is recommended
in patients with paroxysmal, persistent, or permanent AF. The choice of
medication should be individualized and the dose modulated to avoid
bradycardia.34
In patients who experience symptoms related to AF during activity, the adequacy

IC
IC of heart rate control should be assessed during exercise, adjusting
pharmacological treatment as necessary to keep the rate in the physiological
range.
In pre-excitation AF, or in patients with a history of AF, preferred drugs for rate
ICIC control are propafenone or amiodarone
It is reasonable to initiate treatment

45 with a lenient rate control protocol aimed at a
IIbB
resting heart rate <110 bpm.84
In patients who experience symptoms related to AF during activity, the adequacy
IC of heart rate control should be assessed during exercise, adjusting
pharmacological treatment as necessary to keep the rate in the physiological
range.
In pre-excitation AF, or in patients with a history of AF, preferred drugs for rate
IC control are propafenone or amiodarone
It is reasonable to initiate treatment with a lenient rate control protocol aimed at a

IIbB
IIbB
resting heart rate <110 bpm.84
It is reasonable to adopt a stricter rate control strategy when symptoms persist or

IIbB
IIbB tachycardiomyopathy occurs, despite lenient rate control: resting heart rate <80
bpm and heart rate during moderate exercise <110 bpm. After achieving the strict
heart rate target, a 24 h Holter monitor is recommended to assess safety.84
IIa C Digoxin is indicated in patients with heart failure and LV dysfunction, and in
IIaC
sedentary (inactive) patients.
Rate control may be achieved by administration of oral amiodarone when other

IIbC
IIb C
measures are unsuccessful or contraindicated.
Digitalis should not be used as the sole agent to control the rate of ventricular
IIIB
III B response in patients with paroxysmal AF.88
Intravenous administration of amiodarone is recommended to control the heart

IB
IB rate in patients with AF and HF who do not have an accessory pathway.
IIaC Intravenous amiodarone can be useful to control the heart rate in patients with
IIaC AF when other measures are unsuccessful or contraindicated. 35
7.1.2 Combination therapy
Combination of drugs may be required to control heart rate. Care should be

taken to avoid severe bradycardia. The combination of digoxin and ß-blocker
7.1.2 Combination therapy
appears more effective than the combination of digoxin with a CCB.89
Combination of drugs may be required to control heart rate. Care should be
A combination
taken of digoxin
to avoid andbradycardia.
severe either a ß-blocker, diltiazem,
The combination or verapamil
of digoxin is
and ß-blocker
Keypoint
reasonableappears morethe
to control effective
heartthan
ratethe combination
both of digoxin
at rest and duringwith a CCB.89in patients
exercise
with AF.
A combination of digoxin and either a ß-blocker, diltiazem, or verapamil is
IIaB
IIaB reasonable to control the heart rate both at rest and during exercise in patients
<<Figure 11>>
with AF.
<<Figure 11>>
46
Figure 11 : Rate control. COPD = chronic obstructive pulmonary disease. *Small doses of b1-elective
Figure
blockers11may
: Rate control.
be used COPDif=rate
in COPD chronic obstructive
control pulmonary
is not adequate with disease. *Small doses
non-dihydropyridine of b1-elective
calcium channel
blockers mayand
antagonists be digoxin.
used in COPD if rateiscontrol
Amiodarone is notforadequate
also used with in
rate control non-dihydropyridine calcium
patients who do not channel
respond to
antagonists
glycosides, b-blockers or non-dihydropyridine calcium antagonists. Dronedarone may also be used for rateto
and digoxin. Amiodarone is also used for rate control in patients who do not respond
glycosides, b-blockers
control in patient or non-dihydropyridine
with recurrent episodes of atrialcalcium antagonists. Dronedarone may also be used for rate
fibrillation.
control in patient with recurrent episodes of atrial fibrillation.
7.2 NON-PHARMACOLOGICAL RATE CONTROL
7.2.1 AV NODAL ABLATION AND PACING
AV nodal ablation in conjunction with permanent pacemaker implantation

provides highly effective control of the heart rate and improves symptoms, quality
of life, exercise capacity, ventricular function and healthcare utilization in selected
patients with AF.90,100
Ablation of the atrioventricular node is a palliative but irreversible procedure and

is therefore reasonable in patients in whom pharmacological rate control,
including combination of drugs, has failed or rhythm control with drugs and/or LA
ablation has failed.
When the rate of ventricular response to AF cannot be controlled with

pharmacological agents or tachycardia-mediated cardiomyopathy is suspected,
catheter-directed ablation of the AV node may be considered in conjunction with
permanent pacemaker implantation.
It is suggested that programming the pacemaker

47 initially for the 1 st month post-
ablation to a higher nominal rate (90 beat per minutes) will reduce the risk of
including combination of drugs, has failed or rhythm control with drugs and/or LA
ablation hasAblation
failed.of the atrioventricular node is a palliative but irreversible procedure and
is therefore reasonable in patients in whom pharmacological rate control,
When the including
rate ofcombination
ventricular of drugs, has failed or rhythm control with drugs and/or LA
response to AF cannot be controlled with
ablation has failed.
pharmacological agents or tachycardia-mediated cardiomyopathy is suspected,
catheter-directed
When theablation
rate ofof the AV node
ventricular may betoconsidered
response AF cannotinbe conjunction
controlled with
with
permanent pharmacological
pacemaker implantation.
agents or tachycardia-mediated cardiomyopathy is suspected,
catheter-directed ablation of the AV node may be considered in conjunction with
permanent
It is suggested the pacemaker initially for the 1 st month post-
pacemaker implantation.
that programming
ablation to a higher nominal rate (90 beat per minutes) will reducest the risk of
It is suggested that programming the pacemaker initially for the 1 month post-
sudden cardiac death.
ablation to a higher nominal rate (90 beat per minutes) will reduce the risk of
sudden cardiac death.
Keypoints
Ablation of the AV node to control heart rate should be considered when the rate
IIa B be Ablation
cannot
IIaB of thewith
controlled AV node to control heart rate
pharmacological should
agents andbe considered
when AF when the rate
cannot be
prevented bycannot be controlled
antiarrhythmic with pharmacological
therapy or is associated agents
with and when AF
intolerable cannot
side be
effects,
prevented by antiarrhythmic therapy or is associated with intolerable side effects,
and direct catheter-based
and direct
or surgical
catheter-based or
ablation
surgical
of AFofisAF
ablation
not
is
indicated,
not
has
indicated, has
failed,
failed,
or
or
is rejected.90,100
is rejected.90,100
Ablation of Ablation
the AVofnode should
the AV be considered
node should for patients
be considered with
for patients permanent
with permanent AF
AF
IIaB
IIa Ban indication
and an indication
and for CRTfor(NYHA
CRT (NYHA functional
functional classclass III ambulatory
III or or ambulatoryclass
class IV
IV
symptoms
symptoms despite despite optimal medical therapy, LVEF <35%, QRS width >130
101-104 optimal medical therapy, LVEF <35%, QRS width >130
101-104 ms).
ms).
Ablation of the AV node should be considered for CRT non-responders in whom
IIaC
Ablation of AF
theprevents
AV node shouldbiventricular
effective be considered for CRT
stimulation and non-responders in whom
amiodarone is ineffective or
IIa C
AF prevents effective biventricular stimulation and amiodarone is ineffective or
contraindicated.
contraindicated.
In patients with any type of AF and severely depressed LV function (LVEF <35%)
IIaC and severe heart failure symptoms (NYHA III or IV), biventricular stimulation
InIIapatients
C with any type of AF and severely depressed LV function (LVEF <35%)
should be considered after AV node ablation.
and severe heart failure symptoms (NYHA III or IV), biventricular stimulation
should be considered
Ablation of after
the AVAV node
node to
ablation.
control heart rate may be considered when
IIbC
IIb C tachycardia-mediated cardiomyopathy is suspected and the rate cannot be
Ablation ofcontrolled
the AVwithnode to controlagents,
pharmacological heartand
rate may
direct be ofconsidered
ablation when
AF is not indicated,
has failed, or is
tachycardia-mediated rejected.
cardiomyopathy is suspected and the rate cannot be
Ablation of the AV node with consecutive implantation of a CRT device may be
IIbC considered in patients with permanent AF, LVEF <35%, and NYHA functional
IIb C
class I or II symptoms on optimal medical therapy to control heart rate when
pharmacological therapy is insufficient or associated with side effects.
In patients with any type of AF, moderately depressed LV function (LVEF <45%)
IIbC
IIb C and mild heart failure symptoms (NYHA II), implantation of a CRT pacemaker
may be considered after AV node ablation.
In patients with paroxysmal AF and normal LV function, implantation of a dual-

IIbC
IIb C chamber (DDDR) pacemaker with mode-switch function may be considered after
AV node ablation.
In patients with persistent or permanent AF and normal LV function, implantation

IIbC
IIb C of a single- chamber (VVIR) pacemaker may be considered after AV node
ablation.
Catheter ablation of the AV node should not be attempted without a prior trial of
IIIC
III C medication, or catheter ablation for AF, to control the AF and/or ventricular rate in
patients with AF.
8 MANAGEMENT – LONGTERM RHYTHM CONTROL
The term ‘rhythm control’ encompasses the processes of conversion of atrial

brillation (AF) or atrial utter (AFI) to normal sinus rhythm, as well as the
maintenance of sinus rhythm.
Maintenance of sinus rhythm may also be referred to as prevention of AF/AFI

relapse or recurrence, and may be achieved by pharmacological or
nonpharmacological means, or both (hybrid therapy).
In the absence of spontaneous reversion,

48 cardioversion is chosen as part of the
rhythm-control strategy.
The term
The term ‘rhythm
‘rhythm control’
control’ encompasses
encompasses the
the processes
processes of
of conversion
conversion of
of atrial
atrial
brillation (AF)
brillation (AF) or
or atrial
atrial utter
utter (AFI)
(AFI) to
to normal
normal sinus
sinus rhythm,
rhythm, as
as well
well as
as the
the
maintenance of
maintenance of sinus
sinus rhythm.
rhythm.
Maintenance of
Maintenance of sinus
sinus rhythm
rhythm may
may also
also be
be referred
referred to
to as
as prevention of
prevention of AF/AFI
AF/AFI
relapse or
relapse or recurrence,
recurrence, and
and may
may be be achieved
achieved by by pharmacological or
pharmacological or
nonpharmacological means,
nonpharmacological means, or
or both
both (hybrid
(hybrid therapy).
therapy).
In the
In the absence
absence of
of spontaneous
spontaneous reversion,
reversion, cardioversion
cardioversion is
is chosen
chosen as
as part
part of
of the
the
The following
The following are
are the
the guiding
guiding principles
principles of
of antiarrhythmic
antiarrhythmic drug
drug therapy
therapy to
to
maintain sinus
maintain sinus rhythm
rhythm in
in AF:
AF:
(1) Treatment
(1) Treatment is
is motivated
motivated by
by attempts
attempts to
to reduce
reduce AF-related
AF-related symptoms.
symptoms.
(2) Efficacy
(2) Efficacy of
of antiarrhythmic
drugs to
to maintain
maintain sinus
sinus rhythm
rhythm is
is modest.
modest.
(3) Clinically
(3) Clinically successful
successful antiarrhythmic
antiarrhythmic drug
drug therapy
therapy may
may reduce
reduce rather
rather than
than
eliminate recurrence
eliminate recurrence of
of AF.
AF.
(4) If
(4) If one
one antiarrhythmic
antiarrhythmic drug
drug ‘fails’,
‘fails’, a
a clinically
clinically acceptable
acceptable response
response may
may be
be
achieved with
achieved with another
another agent.
agent.
(5) Drug-induced
(5) Drug-induced proarrhythmia
proarrhythmia or
or extra-cardiac
extra-cardiac side
side effects
effects are
are frequent.
frequent.
(6) Safety
(6) Safety rather
rather than
than efficacy
efficacy considerations
considerations should
should primarily
primarily guide
guide the
the choice
choice
of antiarrhythmic
of antiarrhythmic agent
agent
8.1 EFFICACY
8.1 EFFICACY OF
OF ANTIARRHYTHMIC
ANTIARRHYTHMIC DRUGS
DRUGS IN
IN PREVENTING
PREVENTING
RECURRENT ATRIAL
RECURRENT ATRIAL BRILLATION
BRILLATION
In a
In a recent
recent meta-analysis
meta-analysis of of 4444 randomized
randomized controlled
controlled trials
trials comparing
comparing
105
antiarrhythmic drugs against
against control,
control,105 the antiarrhymic
the antiarrhymic drugs
drugs signicantly
signicantly
reduced the
reduced the rate
rate of
of recurrent
recurrent AF.
AF. Overall,
Overall, the
the likelihood
likelihood of
of maintaining
maintaining sinus
sinus
106
rhythm is
rhythm is approximately
approximately doubled
doubled by by the
the use
use ofof antiarrhythmic
antiarrhythmic drugs.
drugs.106
Amiodarone was
Amiodarone was superior
superior to
to class
class II agents
agents and
and sotalol.
sotalol.
The number
The number ofof patients
patients needed
needed toto treat
treat for
for 1
1 year
year was
was 2 2– – 9.
9. Withdrawal
Withdrawal due
due to
to
side effects
side effects was
was frequent
frequent (1
(1 in
in 9
9–– 27
27 patients),
patients), and
and all
all drugs
drugs except
except amiodarone
amiodarone
105
and propafenone
and propafenone increased
increased the
the incidence
incidence ofof proarrhythmia.
proarrhythmia.105 The The number
number of
of
patients needed
patients needed toto harm
harm was
was 17
17 –– 119.
119. Most
Most of
of the
the trials
trials included
included inin the
the analysis
analysis
enrolled relatively healthy patients without severe concomitant cardiac disease.
Although mortality was low in all studies (0 – 4.4%), rapidly dissociating sodium
channel blockers (disopyramide phosphate, quinidine sulfate) were associated
with increased mortality.
8.2 CHOICE OF ANTIARRHYTHMIC DRUGS
Antiarrhythmic therapy for recurrent AF is recommended on the basis of

choosing safer, although possibly less efficacious, medication before resorting to
more effective but less safe therapy. Upon initiation of antiarrhythmic therapy,
regular ECG monitoring is recommended (see Table 16. page 45).
8.2.1 PATIENTS WITH LONE ATRIAL FIBRILLATION
In patients with no or minimal heart disease, ß-blockers represent a logical rst

attempt to prevent recurrent AF when the arrhythmia is clearly related to mental or
physical stress (adrenergic AF). Flecainide, propafenone, sotalol, or dronedarone
is usually prescribed as second line agents (Figure 12, page 50).107,108
<<Figure 12>> 49
enrolled relatively healthy patients without
No or minimal structuralsevere concomitant cardiac disease.
heart disease
enrolled relatively
Although mortality healthy
was lowpatients without
in all studies (0 severe
– 4.4%), concomitant cardiac disease.
rapidly dissociating sodium
Althoughblockers
channel mortality (disopyramide
was low in all phosphate,
studies (0 – quinidine
4.4%), rapidly sulfate)dissociating sodium
were associated
channel
with blockers
increased (disopyramide phosphate, quinidine sulfate) were associated
mortality.
with increased mortality.
Adrenergically mediated Undetermined
Antiarrhythmic therapy B-Blocker for recurrent AF is recommended Dronedaroneon the basis of
Antiarrhythmic
choosing safer, therapy although for recurrent
possibly AF is recommended
less efficacious, on theresorting
Flecainidebefore
medication basis toof
Propafenone
choosing safer, although possibly less efficacious,
more effective but less safe therapy. Upon initiation of Sotalol medication before resorting
antiarrhythmic to
therapy,
more effective
regular but less is
ECG monitoring safe therapy. Upon
recommended (seeinitiation
Table 16.ofpage antiarrhythmic
45). therapy,
regular ECG monitoring Sotalol is recommended (see Table 16. page 45).

In patients withDronedarone
no or minimal heart disease, ß-blockers represent a logical rst
Amiodarone
In patients
attempt with norecurrent
to prevent or minimal AF heart
when disease,
the arrhythmiaß-blockers represent
is clearly relatedatological
mentalrst
or
attempt tostress
physical prevent recurrentAF).
(adrenergic AF when the arrhythmia
Flecainide, propafenone,is clearly related
sotalol, to mental or
or dronedarone
physical
is usuallystress (adrenergic
prescribed as secondAF).line
Flecainide,
agents (Figurepropafenone,
12, pagesotalol, or dronedarone
50).107,108
is usually prescribed as second line agents (Figure 12, page 50).107,108
Figure 12. Choice of antiarrhythmic medication for the patient with AF and no or minimal structural heart
<<Figure 12>> may be initially based on the pattern of arrhythmia onset. Antiarrhythmic agents are
disease. Medication
<<Figure 12>> order within each treatment box.
listed in alphabetical
Adapted with modification from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European
heart Journal 2010; doi:10.1093/eurheartj/ehq278)
8.2.2 PATIENTS WITH UNDERLYING HEART DISEASE
8.2.2 PATIENTS WITH UNDERLYING HEART DISEASE
Cardiovascular disease has conventionally been divided into a variety of
Cardiovascular disease
pathophysiological has conventionally
substrates: been divided
hypertrophy, ischaemia, and into a variety
congestive of
heart
pathophysiological
failure (Figure 13). substrates:
For each ofhypertrophy,
these it has ischaemia, and congestive
been recommended heart
that specic
failure be
drugs (Figure
avoided.13). For each of these it has been recommended that specic
drugs be avoided.
<<Figure 13>>
<<Figure 13>>
Individual drugs and their main disadvantages are listed in Table 17.
Amiodarone is the most efficacious antiarrhythmic drug for the prevention of
Amiodarone
recurrent AF.isHowever,
the mostseveral
efficacious antiarrhythmic
meta-analyses drug
105,109-111 for failed
have the prevention
to identify of
a
105,109-111
recurrent AF.
benecial However,
effect severalon
of amiodarone meta-analyses
cardiovascular outcomes. haveInfailed to the
view of identify a
better
benecial
safety andeffect of amiodarone
potential on cardiovascular
outcome benet, dronedaroneoutcomes. In view ofas
may be preferable thethe
better
rst
safety and potential
antiarrhythmic option,outcome
at leastbenet, dronedarone
in patients may be preferable
with symptomatic AF and as the rst
underlying
antiarrhythmic option,
cardiovascular at least
disease. in patients
Should with symptomatic
dronedarone AF and symptoms,
fail to control underlying
cardiovascular
amiodarone mightdisease. Should dronedarone fail to control symptoms,
then be necessary.
amiodarone might then be necessary.
Dronedarone can be used safely in patients with ACS, chronic stable angina,
Dronedarone heart
hypertensive can be used safely
disease. in patients
Dronedarone with only
should ACS,bechronic
used in stable angina,
maintaining
hypertensive
sinus heartin disease.
rhythm and Dronedarone
whose normal should
heart rhythm hasonly
beenberestored.
used inDronedarone
maintaining
sinus rhythm
should not beand
usedininwhose normal
patients with heart rhythm has been restored. Dronedarone
failure.112
should not be used in patients with heart failure.112
Figure 13. Choice of antiarrhythmic drug according to underlying pathology. ACEI=angiotensin-converting enzyme inhibitor; ARB=
angiotensin receptor blocker; CAD = coronary artery disease; CHF=congestive heart failure; HT=hypertension; LVH =left ventricular
hypertrophy; NYHA=New York Heart Association; unstable=cardiac decompensation within the prior 4 weeks. Antiarrhythmic agents
are listed in alphabetical order within each treatment box. ? = evidence for ‘upstream’ therapy for prevention of atrial remodelling still
remains controversial.
Adapted with modification from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal
50
Cardiovascular disease has conventionally been divided into a variety of
pathophysiological substrates: hypertrophy, ischaemia, and congestive heart
failure (Figure 13). For each of these it has been recommended that specic
drugs be avoided.
<<Figure 13>>
Amiodarone is the most efficacious antiarrhythmic drug for the prevention of

recurrent AF. However, several meta-analyses105,109-111 have failed to identify a
benecial effect of amiodarone on cardiovascular outcomes. In view of the better
safety and potential outcome benet, dronedarone may be preferable as the rst
antiarrhythmic option, at least in patients with symptomatic AF and underlying
cardiovascular disease. Should dronedarone fail to control symptoms,
amiodarone might then be necessary.
Dronedarone can be used safely in patients with ACS, chronic stable angina,
hypertensive heart disease. Dronedarone should only be used in maintaining
sinus rhythm and in whose normal heart rhythm has been restored. Dronedarone
should not be used in patients with heart failure.112
8.2.2.1 Patients with left ventricular hypertrophy
In patients with LV hypertrophy, sotalol is thought to be associated with an

increased incidence of proarrhythmia. Flecainide and propafenone may be used,
but there is some concern about proarrhythmic risk, especially in patients with
marked hypertrophy (LV wall thickness >1.4 cm according to previous
guidelines), and associated coronary artery disease.
Since dronedarone was demonstrated to be safe and well tolerated in a large

study including patients with hypertension and possible LV hypertrophy, it is an
option for this population, although denitive data do not exist. Amiodarone
should be considered when symptomatic AF recurrences continue to impact on
the quality of life of these patients.
8.2.2.2 Patients with coronary artery disease
Patients who have coronary artery disease should not receive ecainide163 or
propafenone. Sotalol or dronedarone should be administered as rst-line therapy.
Dronedarone may be preferred based on its safety prole. Amiodarone is
considered as the drug of last resort in this population due to its extra-cardiac
side effect prole.
8.2.2.3 Patients with heart failure
Amiodarone is the only agents available in Malaysia that can be safely

administered in patients with heart failure.
Dronedarone is contraindicated in patients with all classes of heart failure.112 In

such patients, amiodarone should be used.
The following antiarrhythmic drugs are recommended for rhythm control in

patients with AF, depending on underlying heart disease:
IA x amiodarone21,105,113
IA x dronedarone85,86
IA x ecainide105,114
51
IA x propafenone105,113
sideside
effect
effect
prole.
prole.
Amiodarone is the only agents available in Malaysia that can be safely
administered in Patients
8.2.2.3 patients
8.2.2.3 with
Patients
with heart
with
heart
heartfailure.
failure
failure
Amiodarone
DronedaroneAmiodarone is isthethe
onlyonly
is contraindicated agents
in agents available
patients available
with in
all in
Malaysia
Malaysia
classes thatheart
of that
cancan
be be
safely
failure. safely
112
In
administered
administered
in patients
in patients
withwith
heart
such patients, amiodarone should beheart
failure.
used. failure.
112 112
Dronedarone
Dronedarone is contraindicated
is contraindicated
in patients
in patients
withwith
all all
classes
classes
of heart
of heart
failure.
failure. In In
such
such
patients,
patients,
amiodarone
amiodaroneshould
should
be be
used.
used.
The following antiarrhythmic drugs are recommended for rhythm control in
patients with AF, depending on underlying heart disease:
TheThe
following
following
antiarrhythmic
antiarrhythmic
drugs
drugs
areare
recommended
recommended
for for
rhythm
rhythm
control
control
in in
patients
Keypoints patients
withwith
AF,AF,
depending
depending
on on
underlying
underlying
heart
heart
disease:
disease:
x amiodarone21,105,113
21,105,113
21,105,113
I AIA
IA x amiodarone
x amiodarone
x dronedarone85,86
85,8685,86
I AIA
IA x dronedarone
x dronedarone
x ecainide105,114 105,114
I AIA
IA x ecainide
x ecainide 105,114
105,113
IxApropafenone
I AIA x propafenone 105,113
x propafenone 105,113
21,48,105 21,48,105
I AIA
IxAd,I-sotalol
x d,I-sotalol
x d,I-sotalol 21,48,105
IA/C
I A/C Amiodarone is more effective in maintaining sinus rhythm than sotalol,
propafenone, ecainide (by analogy), or dronedarone (Level of Evidence A), but
because of its toxicity prole should generally be used when other agents have
failed or are contraindicated (Level of Evidence C).21,105,110,113
In patients with severe heart failure, NYHA class III and IV or recently unstable
IB
IB (decompensation within the prior month) NYHA class II, amiodarone should be
the drug of choice.115
In patients without signicant structural heart disease, initial antiarrhythmic

IA
IA therapy should be chosen from dronedarone, ecainide, propafenone, and
sotalol.85,86,105,113-115
IC
IC ȕ-Blockers are recommended for prevention of adrenergic AF.
If one antiarrhythmic drug fails to reduce the recurrence of AF to a clinically

IIaC
IIa C acceptable level, the use of another antiarrhythmic drug should be considered.
Dronedarone should be considered in order to reduce cardiovascular

IIaB
IIa B hospitalizations in patients with non-permanent AF and cardiovascular risk
factors.85,86
IIaC
IIa C ȕ-blockers should be considered for rhythm (plus rate) control in patients with a
rst episode of AF.
Dronedarone is not recommended for treatment of permanent AF and all classes

IIIB
III B
of heart failure.
Antiarrhythmic drug therapy is not recommended for maintenance of sinus

IIIC
III C rhythm in patients with advanced sinus node disease or AV node dysfunction
unless they have a functioning permanent pacemaker.
8.3 NONPHARMACOLOGICAL THERAPY
There is a variety of alternative non-pharmacological therapies for the prevention

and control of AF.
8.3.1 LEFT ATRIAL CATHETER ABLATION
Catheter ablation of AF particularly circumferential pulmonary vein ablation

(isolation) in the left atrium represents a promising and evolving therapy for
selected patients resistant to pharmacological therapy.
Ablation is indicated in highly symptomatic, paroxysmal or persistent AF, despite

optimal medical therapy and in patients with minimal or moderate structural heart
disease.
52
A recent meta-analysis found a 77% success rate for catheter ablation strategies
vs. 52% for antiarrhythmic medication.117 Similar results have been reported in
Catheter ablation of AF particularly circumferential pulmonary vein ablation
(isolation) in the left atrium represents a promising and evolving therapy for
selected patients resistant to pharmacological therapy.
Ablation is indicated in highly symptomatic, paroxysmal or persistent AF, despite

optimal medical therapy and in patients with minimal or moderate structural heart
disease.
A recent meta-analysis found a 77% success rate for catheter ablation strategies
vs. 52% for antiarrhythmic medication.117 Similar results have been reported in
other meta-analyses,118,-120 one of which showed that PV isolation for paroxysmal
or persistent AF was associated with markedly increased odds of freedom from
AF at 1 year.119
Ablation may particularly benefit younger patients with lone AF who are
frequently symptomatic and for whom long-term antiarrhythmic poses higher risk
and lifestyle cost.
For patients with either persistent AF or long-standing persistent AF, and no or

minimal organic heart disease, the treatment strategies and the benet – risk
ratio of catheter ablation are less well established. Extensive and frequently
repeated ablation procedures may be necessary in these patients, and it seems
reasonable to recommend that they should be refractory to antiarrhythmic drug
treatment before ablation is considered (See Figure 14).
<<Figure 14>>
Adapted with modification from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal 2010;
Figure 14. Choice between ablation and antiarrhythmic drug therapy for patients with and without structural heart disease. Proposed integration
each treatment box. Please note that left atrium (LA) ablation as first-line therapy (dashed line) is a Class IIb recommendation for patients with
disease, including hypertension (HT) without left ventricular hypertrophy (LVH). †More extensive LA ablation may be needed; *usually PVI is
hypertrophy; NYHA=New York Heart Association; PVI=pulmonary vein isolation. Antiarrhythmic agents are listed in alphabetical order within
of antiarrhythmic drug and catheter ablation for AF in patients with relevant underlying heart disease and for those with no or minimal heart
paroxysmal AF and no or minimal heart disease, who remain highly symptomatic, despite rate control, and who reject antiarrhythmic drug
For symptomatic paroxysmal and persistent AF in patients with relevant organic
appropriate. AF= atrial fibrillation; CAD = coronary artery disease; CHF = congestive heart failure; HT=hypertension; LVH=left ventricular
heart disease, antiarrhythmic drug treatment is recommended before catheter
ablation. In such patients, successful ablation is more difficult to achieve. Major
symptoms should be associated with the arrhythmia to justify the procedure.
Ablation of persistent and long-standing persistent AF is associated with variable
but encouraging success rates, but very often requires several attempts.
Ablation of common atrial utter is recommended as part of an AF ablation

IB procedure if documented prior to the ablation procedure or occurring during the
AF ablation.18
Catheter ablation for paroxysmal AF should be considered in symptomatic

IIa A
therapy.
53
Ablationheart
minimal organic may disease,
particularlythe
benefit younger
treatment patients and
strategies with the
lone benet
AF who– are
risk
frequently symptomatic and for whom long-term antiarrhythmic poses higher risk
ratio of catheter ablation
and lifestyle cost.
are less well established. Extensive and frequently
reasonableForto patients
recommend that persistent
with either they shouldAF orbe refractory to
long-standing antiarrhythmic
persistent drug
AF, and no or
treatment before
minimalablation is considered
organic heart (See
disease, the Figure strategies
treatment 14). and the benet – risk
ratio of catheter ablation are less well established. Extensive and frequently
<<Figure 14>>
reasonable to recommend that they should be refractory to antiarrhythmic drug
treatment before ablation is considered (See Figure 14).
For symptomatic paroxysmal and persistent AF in patients with relevant organic
heart disease, antiarrhythmic
<<Figure 14>> drug treatment is recommended before catheter
For symptomatic paroxysmal
symptoms should be associated with and the
persistent AF in patients
arrhythmia with the
to justify relevant organic
procedure.
Ablation ofheart disease,
persistent antiarrhythmic
and long-standingdrugpersistent
treatment AF
is recommended
is associatedbeforewith catheter
variable
but encouraging
symptomssuccess
shouldrates, but very often
be associated requires
with the several
arrhythmia attempts.
to justify the procedure.
Ablation of persistent and long-standing persistent AF is associated with variable
Ablation ofbutcommon
Keypoints atrial
encouraging utter
success is but
rates, recommended as part
very often requires of attempts.
several an AF ablation
procedure if documented prior to the ablation procedure or occurring during the
18
Ablation of common atrial utter is recommended as part of an AF ablation
AF ablation.
IIB
B procedure if documented prior to the ablation procedure or occurring during the
AF ablation.18
IIaA
IIa A
patients who have previously failed a trial of antiarrhythmic medication.31,117,122-125
Ablation of persistent symptomatic AF that is refractory to antiarrhythmic therapy

IIaB
IIa B should be considered a treatment option.18
In patients post-ablation, LMWH or i.v. UFH should be considered as ‘bridging

therapy’ prior to resumption of systemic OAC, which should be continued for a
IIaC
IIa C minimum of 3 months. Thereafter, the individual stroke risk factors of the patient
should be considered when determining if OAC therapy should be continued.
Continuation of OAC therapy post- ablation is recommended in patients with 1

IIaB
IIa B ‘major’ (‘denitive’) or >2 ‘clinically relevant non-major’ risk factors (i.e. CHA
126
2DS2-VASc score >2).
IIbC
IIb C Catheter ablation of AF may be considered in patients with symptomatic long-
standing persistent AF refractory to antiarrhythmic drugs.
IIbB Catheter ablation of AF in patients with heart failure may be considered when
IIb B
antiarrhythmic medication, including amiodarone, fails to control symptoms.29,30
Catheter ablation of AF may be considered prior to antiarrhythmic drug therapy in

IIbB
IIb B symptomatic patients despite adequate rate control with paroxysmal symptomatic
AF and no signicant underlying heart disease.117
8.3.2 SURGICAL ABLATION
The major 8.3.2

indication for surgical
SURGICAL ABLATIONablation of AF is the presence of both AF and
the requirement for cardiac surgery for structural heart disease.120,127,128 Stand-
alone surgery for AFindication
The major shouldforbesurgical
considered
ablationfor symptomatic
of AF AF ofpatients
is the presence both AF whoand
120,127,128
prefer a surgical approach,
the requirement forhave failed
cardiac one for
surgery or structural
more attempts at catheter ablation,
heart disease. Stand-
or who are alone surgery for for
not candidates AFcatheter
should be considered for symptomatic AF patients who
ablation.
prefer a surgical approach, have failed one or more attempts at catheter ablation,
or who are not candidates for catheter ablation.
Keypoints
Surgical ablation of AF should be considered in patients with symptomatic AF
120,127,128
undergoingSurgical
cardiacablation
surgery.
of AF should be considered in patients with symptomatic AF
IIaA
IIa A 120,127,128
undergoing cardiac surgery.
Surgical ablation of AF may be performed in patients with asymptomatic AF
Surgical ablation of AF may be performed in patients with asymptomatic AF
undergoing
IIbC
IIb C cardiac surgery if feasible with minimal risk.
undergoing cardiac surgery if feasible with minimal risk.
Minimally invasive
Minimallysurgical ablationablation
invasive surgical of AF of without concomitant
AF without cardiac
concomitant cardiacsurgery is
surgery is
feasible
IIb C and
IIbC may be
feasible and performed in patients
may be performed with with
in patients symptomatic AFAFafter
symptomatic afterfailure of
failure of
catheter ablation.
catheter ablation.
8.3.3 SUPPRESSION OF AF THROUGH PACING

8.3.3 SUPPRESSION OF AF THROUGH 54 PACING
Several studies have examined the role of atrial pacing to prevent recurrent
Surgical ablation
Surgical of AF may
ablation of AFbe performed
should in patients
be considered with with
in patients asymptomatic
symptomatic AF
AF
IIb C IIa A
undergoing cardiac surgery
undergoing if feasible
cardiac surgery. with minimal risk.
120,127,128
Surgical ablation
Minimally invasive surgicalofablation
AF mayofbeAF performed in patients with
without concomitant asymptomatic
cardiac surgeryAFis
IIb C undergoing
IIb C feasible and may becardiac surgery
performed inifpatients
feasible with
withminimal risk.
symptomatic AF after failure of
catheter ablation.
Minimally invasive surgical ablation of AF without concomitant cardiac surgery is
IIb C feasible and may be performed in patients with symptomatic AF after failure of
8.3.3 SUPPRESSION OF AF THROUGH PACING
catheter ablation.
8.3.3 SUPPRESSION
Several studies have examined OF AFtheTHROUGH PACING
role of atrial pacing to prevent recurrent
paroxysmal AF. In patients with symptomatic bradycardia, the risk of AF is lower
Several studies have examined129 the role of atrial pacing to prevent recurrent
with atrial than with ventricular pacing. In patients with sinus node dysfunction
paroxysmal AF. In patients with symptomatic bradycardia, the risk of AF is lower
and normalwithAVatrial than with data
conduction, frompacing.
ventricular several
129 randomized trials support atrial or
In patients with sinus node dysfunction
dual-chamberand rather
normal than ventricular
AV conduction, datapacing for prevention
from several randomized AF.130-133
oftrials supportPatients
atrial or
with paroxysmal AF rather
dual-chamber and symptomatic
than ventricular bradycardia shouldof be
pacing for prevention referred
AF.130-133 for
Patients
electrophysiological review AF
with paroxysmal for consideration
and symptomatic of atrial based pacing.
bradycardia should be referred for
electrophysiological review for consideration of atrial based pacing.
Keypoint
When ventricular pacing with dual-chamber devices is unavoidable because of
When ventricular pacing with dual-chamber devices is unavoidable because of
IIaB IIaB
concomitant disease of the AV
IIaB concomitant disease of conduction system,
the AV conduction the the
system, evidence
evidence is isless
lessclear
clear that
that
pacing ispacing
atrial-basedatrial-based superior. Although
is superior. atrial-based
Although pacing
atrial-based is associated
pacing is associatedwithwith aa
lower burdenlowerofburden
AF and of AFstroke risk compared
and stroke risk comparedto ventricular-based
to ventricular-basedpacingpacing in
in
patients requiring
patients requiring pacemakerspacemakers for bradyarrhythmias,
for bradyarrhythmias, the the value
value ofofpacing
pacing as
as aa
primaryfor
primary therapy therapy for prevention
prevention of recurrent
of recurrent AF has AF not
has been
not been proven.
proven.
8.4 UPSTREAM THERAPY
Upstream therapy is a term used that relates to prevention or delaying of

myocardial remodelling associated with hypertension, heart failure, or
inammation (e.g. after cardiac surgery) and therefore may deter the
development
8.4 of new AF THERAPY
UPSTREAM (primary prevention) or, once established, its rate of
recurrence or progression to permanent AF (secondary prevention).135
Upstream therapy is a term used that relates to prevention or delaying of
Treatmentsmyocardial remodelling associated
with angiotensin-converting with inhibitors
enzyme hypertension, heart angiotensin
(ACEIs), failure, or
inammation (e.g. after cardiac surgery) and therefore may deter the
receptor blockers (ARBs), aldosterone antagonists, statins, and omega-3
development of new AF (primary prevention) or, once established, its rate of
polyunsaturated fattyor progression
recurrence acids (PUFAs) are usually
to permanent referred
AF (secondary to as 135‘upstream’
prevention).
therapies for AF.
Treatments with angiotensin-converting enzyme inhibitors (ACEIs), angiotensin
8.4.1 ANGIOTENSIN-CONVERTING ENZYME INHIBITORS
receptor blockers (ARBs), aldosterone AND and omega-3
antagonists, statins,
polyunsaturated
ANGIOTENSIN RECEPTOR fattyBLOCKERS
acids (PUFAs) are usually referred to as ‘upstream’
therapies for AF.
Primary prevention
8.4.1 ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND
ANGIOTENSIN RECEPTOR BLOCKERS
In patients with congestive cardiac failure, several meta-analyses have shown
a signicant 30 – prevention
Primary 48% reduction in risk of AF associated with ACEI and ARB
therapies.136-140
In patients with congestive cardiac failure, several meta-analyses have shown
a signicant 30 – 48% reduction in risk of AF associated with ACEI and ARB
While in patients with hypertension, in meta-analyses, the overall trend was in
therapies.136-140
favour of ACEI- or ARB-based therapy, but only one meta-analysis has shown a
statistically While
signicant 25%with
in patients reduction in RR of
hypertension, in incident AF.138the overall trend was in
meta-analyses,
favour of ACEI- or ARB-based therapy, but only one meta-analysis has shown a
ACEIs andstatistically
Keypoints ARBs should be25%
signicant considered
reduction infor
RR prevention
of incident AF.of138new-onset AF in
IIa A
patients with heart failure and reduced ejection fraction.136-140
IIaA ACEIs and ARBs should be considered for prevention of new-onset AF in
IIa A
IIa B ACEIs and ARBs should be considered for prevention of new-onset AF in
138,141,142
patients with hypertension,
ACEIs and ARBs particularly with left ventricular
should be considered hypertrophy.
for prevention of new-onset AF in
IIaB
IIa B 138,141,142
patients with hypertension, particularly with left ventricular hypertrophy.
Upstream therapies with ACEIs, ARBs, and statins are not recommended for
III C primary Upstream therapies with ACEIs, ARBs, and statins are not recommended for
IIIC
III C prevention of AF in patients without cardiovascular disease.
primary prevention of AF in patients without cardiovascular disease.
Secondary prevention
55
Several relatively small prospective
Several relatively randomized
small prospective randomizedcontrolled
controlled trials
trials have
have
demonstrated that therapy
demonstrated that with ACEI/ARB
therapy conferred
with ACEI/ARB an additional
conferred benet
an additional beneton onrisk
risk
ACEIs and ARBs should be considered for prevention of new-onset AF in

patients with hypertension, particularly with left ventricular hypertrophy.138,141,142
Upstream therapies with ACEIs, ARBs, and statins are not recommended for
primary prevention of AF in patients without cardiovascular disease.
Several relatively small prospective randomized controlled trials have

demonstrated that therapy with ACEI/ARB conferred an additional benet on risk
of recurrent AF after cardioversion when co-administered with antiarrhythmic
drug therapy, usually amiodarone, compared with an antiarrhythmic drug
alone.143,144 Meta-analyses driven by these studies have reported a signicant 45
– 50% reduction in RR of recurrent AF.136-139 Conversely, a double-blind,
placebo-controlled study failed to demonstrate any benet of therapy with
candesartan for promotion of sinus rhythm after cardioversion in patients who did
not receive antiarrhythmic drug therapy. 145
Evidence to support the use of ACEI/ARB in patients with paroxysmal or

persistent AF who are not undergoing electrical cardioversion remains
controversial.
persistent Evidence
AFwithwho to are
support theundergoing
notARBsuse of ACEI/ARB in patients
electrical with paroxysmal or
Pre-treatment
persistentACEIs
AF whoand are notmay be considered
undergoing incardioversion
electrical patients remains
with recurrent
cardioversion remains
controversial.
AF and receiving antiarrhythmic drug therapy.136-138,143,144
Keypoints controversial.
Pre-treatment
Evidence
ARBs or ACEIs to with
supportACEIs
Pre-treatment
may the
with
be anduseARBs
ACEIs
useful of may
ARBsbe
ACEI/ARB
andprevention
for may considered
be
ofinconsidered
patients
recurrentin patients
with
patients with
withrecurrent
paroxysmal
inparoxysmal AF or or
recurrent in
IIbB 136-138,143,144
AF IIband
B receiving
persistent
patients AF
withAF antiarrhythmic
andwho
receiving
persistent are
AF not drug
antiarrhythmic therapy.
undergoing
undergoing drug therapy.
electrical
136-138,143,144
electrical
cardioversion cardioversion
in the remains
absence of
controversial.
signicant structural
persistent heart
AF who disease ifnotthese
areuseful agents are
undergoing indicated
electrical for other reasons
cardioversion remains
ARBs ARBs or
or ACEIs mayACEIs
be may
useful
136,146,147 be for
for prevention prevention of recurrent
of recurrent paroxysmal AF
paroxysmal AF or in
or in
(e.g.
IIbB hypertension).
controversial.
patients with persistent AF undergoing electrical cardioversion in the absence of
IIb B
patients with persistent AF undergoing electrical cardioversion in the absence of
Pre-treatment with ACEIs and ARBs may
signicant structural heart disease if these be considered in patients with
agents are indicated for other reasonsrecurrent
AF and receiving
Pre-treatment
(e.g. heart
withdisease
antiarrhythmic
hypertension). ACEIs drug
and
136,146,147 if these
therapy.
ARBs agents
may are indicated
136-138,143,144
be considered for other
in patients reasons
with recurrent
136,146,147
IIb Bhypertension).
(e.g.
8.4.3 AF and receiving
STATINS antiarrhythmic drug therapy.136-138,143,144
ARBs or ACEIs may be useful for prevention of recurrent paroxysmal AF or in
ARBsSTATINS
8.4.3 or ACEIs may be useful for prevention of recurrent paroxysmal AF or in
patients
For with persistentpersistent
post-operative
patients withAF,
AFa undergoing
recent electrical
systematic
AF undergoing
cardioversion
review,
electrical
148
have in
cardioversion
the absence
reported a lower
in the absence
of
of
IIb BSTATINS
8.4.3
incidence signicant
of new
For
heart
onset disease
AF
structural
post-operative heart
AF, a
if
favouring these
disease
recent if agents
statins.
these
systematic
are
Some
agents indicated
are
review, studies,
indicated
148
have
forreported
forother
other reasons
particularly
reasons
a lowerin
136,146,147136,146,147
(e.g.
patientshypertension).
with LVhypertension).
(e.g.
incidencedysfunction and heart
of new onset AF favouringfailure, statins.
have shown Some astudies,
20 – 50% reduction
particularly in
For post-operative AF, a recent 149systematic review,148 have reported a lower
in the incidence
patientsofwith
new-onset AF. and heart failure, have shown a 20 – 50% reduction
LV dysfunction
incidence of new
in the onsetof AF
incidence favouring
new-onset AF.149 statins. Some studies, particularly in
patients 8.4.3
with LV STATINS
dysfunction and heart failure, have shown a 20
8.4.3
Statins STATINS
should be considered for prevention of new-onset AF– 50%after reduction
coronary
in the
artery
IIa
Statinsofshould
B incidence
bypass new-onset
grafting, AF.149
be considered
isolated orrecentinforcombination
prevention of new-onset
with148valvular AF after coronary
interventions.
For post-operative AF, a systematic
artery bypass grafting, isolated or in combination review, have reported a lower
148with valvular interventions.
For post-operative
148,150
incidence ofAF,
148,150 newa onset
recentAFsystematic review,Some
favouring statins. have reported
studies, a lower
particularly in
Statins
incidence should
of new
patientsbewith
considered
onset for and
AF favouring
LV dysfunction prevention
heart statins. of Some
failure, new-onset
have shown aAF
studies, 20 – after
50% coronary
particularly
reduction in
artery
patientsbypass
Keypoints
Statins with
may in LVbegrafting,
the
Statins may beisolated
dysfunction
incidence ofconsidered
considered new-onset or
for heart
and in failure,
AF.
prevention
for combination
149
preventionofhave with valvular
of shown
new-onset
new-onset aAF20 – in
AFin interventions.
50% reduction
patients
patients with
with
IIb B
148,150 149
in the incidence
underlying heart of
underlying new-onset AF.particularly
heart disease,
disease, particularly heart heart 151,152
failure.
failure.
151,152
Statins should be considered for prevention of new-onset AF after coronary

IIaB
IIa B
Statins artery
8.4.4 bypass grafting, isolated orFATTY
POLYUNSATURATED in combination
ACIDS with
ANDvalvular interventions.
inALDOSTERONE
8.4.4 mayshouldbebe considered
consideredforforprevention
POLYUNSATURATED
148,150 of ofnew-onset
preventionACIDS
FATTY new-onset
AND AF
AF patients
after
ALDOSTERONE with
coronary
underlying ANTAGONIST
heartgrafting,
disease,isolated
particularly heart failure.151,152
artery bypass
ANTAGONIST or in combination with valvular interventions.
148,150
Statins maythere
At present, be is
considered
no robust for prevention
evidence of any
to make new-onset AF in patients
recommendation for the with
use
IIbB
IIb
8.4.4B POLYUNSATURATED FATTY ACIDS AND prevention
151,152
ALDOSTERONE
At present,underlying
there
of PUFAs heart
is or
no disease,
robust particularly
evidence
aldosterone heart
to for
antagonist make failure.
anyorrecommendation
primary secondary for ofthe
AF.use
ANTAGONIST
Statins
of PUFAsmay be considered
or aldosterone for prevention
antagonist for primary of ornew-onset
secondaryAF in patients
prevention of AF. with
8.4.4 POLYUNSATURATED FATTY
underlying heart disease, particularly heart failure. ACIDS
151,152 AND ALDOSTERONE
At present,ANTAGONIST
there is no robust evidence to make any recommendation for the use
of PUFAs
8.4.4 or aldosterone antagonistFATTY
POLYUNSATURATED
At present, there is no robust
for primary
evidence to
or secondary
ACIDS
make any AND
prevention of AF.
ALDOSTERONE
recommendation for the use
ANTAGONIST of PUFAs or aldosterone antagonist for primary or secondary prevention of AF.
At present, there is no robust evidence to make any recommendation for the use
of PUFAs or aldosterone antagonist for primary or secondary prevention of AF.
56
9 MANAGEMENT – SPECIAL POPULATIONS
9.1 POST-OPERATIVE AF
Although AF may occur after noncardiac surgery, the incidence of atrial

arrhythmias including AF after open-heart surgery is between 20% and 50%.
Post-operative AF usually occurs within 5 d of open-heart surgery, with a peak
incidence on the second day. The arrhythmia is usually self-correcting, and sinus
rhythm resumes in more than 90% of patients by 6 to 8 wk after surgery.
A systematic review of 58 studies in 8565 patients has shown that interventions

to prevent and/or treat post-operative AF with ß-blockers, sotalol, or amiodarone
and, less convincingly, atrial pacing, are favoured with respect to outcome. 153
9.1.1 PREVENTION OF POST-OPERATIVE ATRIAL FIBRILLATION
ß-Blocker therapy is most effective when provided both before and after cardiac
surgery compared with only before or after surgery.153-155 Withdrawal of ß-
blockers is a signicant risk factor for the development of post-operative AF and
should be avoided. Treatment should be started at least 1 week before surgery
with a ß-blocker without intrinsic sympathomimetic activity.
Prophylactic amiodarone decreased the incidence of post- operative AF156. The

benecial effect of amiodarone has been consistently demonstrated in a
systematic review.153The adverse effects of perioperative prophylactic i.v.
amiodarone include an increased probability of post-operative bradycardia and
hypotension.153
Sotalol has been reported to reduce the incidence of post-operative AF by 64%

compared with placebo.153 However, the use of sotalol places patients at risk of
bradycardia and torsade de pointes, especially those with electrolyte
disturbances, and its use in post-operative AF is limited.
Meta-analyses demonstrated that corticosteroid therapy was associated with a

26 – 45% reduction in post-operative AF and shorter hospital stay. 157 However,
the potential adverse effects on glucose metabolism, wound healing, and
infection, make their use for prevention of AF as controversial.
One meta-analysis of eight trials has shown that prophylactic atrial pacing
reduced the incidence of post-operative AF regardless of the atrial pacing site or
pacing algorithm used. 153
9.1.2 TREATMENT OF POST-OPERATIVE ATRIAL FIBRILLATION
In haemodynamically stable patients, the majority will convert spontaneously to

sinus rhythm within 24 h. Initial management includes correction of predisposing
factors (such as pain management, haemodynamic optimization, weaning of i.v.
inotropes, correcting electrolytes and metabolic abnormalities, and addressing
anaemia or hypoxia) where possible.158
In the highly symptomatic patient or when rate control is difficult to achieve,

cardioversion may be performed. DCCV is 95% successful but pharmacological
cardioversion is more commonly used. Amiodarone was shown to be more
effective than placebo in converting post-operative AF to sinus rhythm.
57
Short-acting ß-blockers (e.g. esmolol) are particularly useful when
factors (such as pain management, haemodynamic optimization, weaning of i.v.

factors
cardioversion may(such as pain management,
be performed. DCCV ishaemodynamic
95% successfuloptimization, weaning of i.v.
but pharmacological
cardioversion is more commonly used. Amiodarone was shown to be more
effective than placebo in converting post-operative AF to sinus rhythm.
Short-actingcardioversion
ß-blockersmay be (e.g. esmolol)
performed. DCCV areis 95%particularly
successful but useful when
pharmacological
haemodynamiccardioversion is more
instability is a commonly
concern. used.
OtherAmiodarone was shown
atrioventricular nodalto blocking
be more
effective than placebo in converting post-operative AF to sinus
agents, such as non-dihydropyridine calcium channel antagonists, can be used rhythm.
as alternatives, but digoxin is less effective when adrenergic tone is high. The
Short-acting ß-blockers (e.g. esmolol) are particularly useful when
agents usedhaemodynamic
for rate control of AF following
instability cardiac
is a concern. surgery
Other are listednodal
atrioventricular in Table 15.
blocking
agents, such as non-dihydropyridine calcium channel antagonists, can be used
A number asof alternatives,
studies have but shown
digoxin an increased
is less effective risk
whenofadrenergic
stroke intone
patients
is high.after
The
cardiac surgery. Anticoagulation
agents used for rate controlwith
of AFheparin
followingor VKAsurgery
cardiac is appropriate
are listed inwhen
Table AF
15.
persists longer than 48 h.159 Standard precautions regarding anticoagulation
A number of studies have shown an increased risk of stroke in patients after
pericardioversion should be used (see Section 4.3).
cardiac surgery. Anticoagulation with heparin or VKA is appropriate when AF
persists longer than 48 h.159 Standard precautions regarding anticoagulation
pericardioversion should be used (see Section 4.3).
Keypoints
Oral ȕ-blockers are recommended to prevent post-operative AF for patients
undergoing cardiac surgery in the absence of contraindications.153,154
I AIA Oral ȕ-blockers are recommended to prevent post-operative AF for patients
153,154
undergoing
If used, ȕ-blockers cardiac
(or othersurgery in the absence ofdrugs
oral antiarrhythmic contraindications.
for AF management) are
154,155
recommended to be continued until the day of surgery.
If used, ȕ-blockers (or other oral antiarrhythmic drugs for AF management) are
I BIB
recommended to be continued until the day of surgery. 154,155
Restoration of sinus rhythm by DCCV is recommended in patients who develop
post-operative
I CIC AF andofare
Restoration haemodynamically
sinus rhythm by DCCV isunstable.
recommended in patients who develop
post-operative AF and are haemodynamically unstable.
Ventricular rate control is recommended in patients with AF without
Ventricular rate 155control is recommended in patients with AF without
haemodynamic
I BIB instability.
haemodynamic instability.155
Pre-operative administration
Pre-operative of amiodarone
administration should
of amiodarone be considered
should be considered asasprophylactic
prophylactic
IIaA
therapy
IIa A for therapy
patientsforatpatients
high risk for post-operative
at high AF.153,154,160
risk for post-operative AF.153,154,160
Unless
IIaA
IIa A Unless contraindicated,
contraindicated, antithrombotic/anticoagulation
antithrombotic/anticoagulation medication for
medication for post-
post-
159
operative AF should be considered when the duration of AF is >48 hours.
operative AF should be considered when the duration of AF is >48 hours.159
If sinus rhythm is restored successfully, duration of anticoagulation should be for
IIaB
If IIa
sinus
B rhythm is restored
a minimum of 4 successfully,
weeks but moreduration of anticoagulation
prolonged in the presenceshould be risk
of stroke for
a minimumfactors.
of 4159weeks but more prolonged in the presence of stroke risk
159
factors.
Antiarrhythmic medications should be considered for recurrent or refractory
IIaC
IIa C
postoperative AF in an attemptbe
to maintain sinus rhythm.
Antiarrhythmic medications should considered for recurrent or refractory
postoperative
Sotalol may AF considered
Sotalol
be in an be
may attempt to prevention
for maintain
considered sinus
for prevention
of rhythm.
AFof after
AF after cardiacsurgery,
cardiac surgery, but
but is
is
IIbA
IIb A 153
associated associated with risk of proarrhythmia.
with risk of proarrhythmia.153
Biatrial pacing may be considered for prevention of AF after cardiac surgery.153
IIbA
IIb A
Biatrial pacing may be considered for prevention of AF after cardiac surgery.153
Corticosteroids may be considered in order to reduce the incidence of AF after
IIbB
IIb B 157
Corticosteroids may
cardiac be considered
surgery, in order
but are associated with to reduce the incidence of AF after
risk.
cardiac surgery, but are associated with risk.157 161
Atrial flutter is less common than AF after cardiac surgery, but
pharmacological therapy is similar. Prevention of postoperative atrial flutter is as
161
Atrial flutter is asless
difficult common
prevention of AF, than AFoverdrive
but atrial after pacing
cardiac surgery,useful
is generally but
for
pharmacological therapy
termination is similar.
of atrial Prevention
flutter when of postoperative
epicardial electrodes atrial flutter is as
are in place.
difficult as prevention of AF, but atrial overdrive pacing is generally useful for
termination of atrial flutter when epicardial electrodes are in place.
9.2 ACUTE CORONARY SYNDROME
9.2 ACUTEAF
CORONARY SYNDROME
occurs with an 58
incidence between 2 to 21% in patients with ACS162 and is
more commonly associated with ACS in older patients and those with higher
162
Ib B
cardiac surgery, but are associated with risk.157
Sotalol may be considered for prevention of AF after cardiac surgery, but is
IIb A associated with risk of proarrhythmia.153
Atrial flutter is less common than AF after cardiac surgery,161 but
pharmacological
Biatrialtherapy is similar.
pacing may Prevention
be considered of postoperative
for prevention atrial flutter
of AF after cardiac is153as
surgery.
IIb A
termination
IIb B of atrial fluttermay
Corticosteroids whenbe epicardial
considered electrodes are in place.
in order to reduce the incidence of AF after
cardiac surgery, but are associated with risk.157
Atrial flutter is less common than AF after cardiac surgery,161 but

9.2 ACUTEpharmacological
CORONARY SYNDROME
therapy is similar. Prevention of postoperative atrial flutter is as
termination of atrial flutter when epicardial electrodes are in place.
AF occurs with an incidence between 2 to 21% in patients with ACS162 and is
more commonly associated with ACS in older patients and those with higher
9.2 LV
heart rate and ACUTE CORONARY
dysfunction. 162 SYNDROME
AF is associated with increased in-hospital mortality in the setting of ACS.162Stroke

AF occurs with an incidence between 2 to 21% in patients with ACS and is
rates are also increased
more commonlyin associated
patients with
withACS
ACSand AF. patients and those with higher
in older
heart rate and LV dysfunction.162
Specific recommendations for management of patients with AF in the setting of
ACS are based
AF is primarily
associatedon consensus,
with becausemortality
increased in-hospital no adequate trials ofhave
in the setting ACS.tested
Stroke
rates are also increased in patients with ACS and AF.
alternative strategies.
Specific recommendations for management of patients with AF in the setting of
Direct-current cardioversion is recommended for patients with severe
ACS are based primarily on consensus, because no adequate trials have tested
C
hemodynamic compromise
Keypoints alternative strategies.or intractable ischemia, or when adequate rate
control cannot be achieved with pharmacological agents in patients with ACS
and AF. Direct-current cardioversion is recommended for patients with severe
ICIC hemodynamic compromise or intractable ischemia, or when adequate rate
Intravenouscontrol
beta cannot be achieved with pharmacological agents in patients with ACS
blockers and nondihydropyridine calcium antagonists are
C and AF.
recommended to slow a rapid ventricular response to AF in patients with ACS
who do not Intravenous
have LV dysfunction, bronchospasm,
beta blockers or AV block.
and nondihydropyridine calcium antagonists are
IC
IC recommended to slow a rapid ventricular response to AF in patients with ACS
C Intravenouswho
amiodarone
do not haveisLV
recommended to slow a rapid
dysfunction, bronchospasm, or AVventricular
block. response to
AF and improve LV function in patients with ACS.
IC
IC Intravenous amiodarone is recommended to slow a rapid ventricular response to
AF and improve LV function in patients with ACS.
Intravenous administration of non-dihydropyridine calcium antagonists
Ia C (verapamil, Intravenous
diltiazem) should be considered to slow a rapid ventricular response
administration of non-dihydropyridine calcium antagonists
toIIa
AF
IIaCC in patients with ACS
(verapamil, and should
diltiazem) no clinical signs of heart
be considered to slowfailure.
a rapid ventricular response
to AF in patients with ACS and no clinical signs of heart failure.
Intravenous administration of digoxin may be considered to slow a rapid
Ib C Intravenousin administration of digoxin may be considered to slow a rapid
ventricular
IIbC
IIb C response patients with ACS and AF associated with heart failure.
ventricular response in patients with ACS and AF associated with heart failure.
III B Administration
IIIB
III B of ecainide
Administration or propafenone
of ecainide is notisrecommended
or propafenone in in
not recommended patients
patientswith
with
AF in the setting ACS.163
of setting
AF in the of ACS.163
9.3 WOLFF-PARKINSON-WHITE (WPW) PRE-EXCITATION SYNDROMES̘

9.3 WOLFF-PARKINSON-WHITE (WPW) PRE-EXCITATION SYNDROMES̘
Since accessory pathways (AP) lack the decremental conduction properties of

Since accessory
the AV pathways (AP)with
node, patients lackovert
the pre-excitation
decrementaland conduction
AF are atproperties of
risk of rapid
conduction
the AV node, across
patients theovert
with AP, resulting in fast ventricular
pre-excitation and AFrates areandat possible
risk ofsudden
rapid
conductioncardiac
acrossdeath (SCD)
the AP, because
resulting in of degeneration
fast ventricularinto
ratesventricular brillation.
and possible This
sudden
makes AF in this patient cohort a potentially life-threatening arrhythmia. For
cardiac death (SCD) because of degeneration into ventricular brillation. This
information relating to acute and long-term pharmacological rate control in
makes AF patients
in thiswith
patient
an AP,cohort a potentially
see Section 5.1.1, pagelife-threatening
18. arrhythmia. For
patients with an SUDDEN
9.3.1 AP, see DEATH
SectionAND
5.1.1, page
RISK 18.
STRATIFICATION
The incidence
9.3.1 SUDDEN DEATH of SCDRISK
AND in patients with the Wolff – Parkinson – White syndrome
STRATIFICATION
has ranged from 0.15 to 0.39% over 3- to 22-year follow-up.
The incidence of SCDofinincreased
The markers patientsrisk
with
are:the Wolff – Parkinson – White syndrome
has ranged from 0.15 topre-excited
x Shortest 0.39% over RR3-interval
to 22-year
<250 follow-up.
ms during spontaneous or induced
AF.
The markers ofxAincreased risk are: tachycardia.
history of symptomatic
x Shortest xpre-excited
The presenceRR intervalAPs.
of multiple <250 ms during spontaneous or induced
AF. x Ebstein’s anomaly. 59
x A history of symptomatic tachycardia.
Since accessory pathways (AP) lack the decremental conduction properties of
the AV node, patients with overt pre-excitation and AF are at risk of rapid
conduction across the AP, resulting in fast ventricular rates and possible sudden
cardiac death (SCD) because of degeneration into ventricular brillation. This
makes AF in this patient cohort a potentially life-threatening arrhythmia. For
patients with an AP, see Section 5.1.1, page 18.
9.3.1 SUDDEN DEATH AND RISK STRATIFICATION
The incidence of SCD in patients with the Wolff – Parkinson – White syndrome
has ranged from 0.15 to 0.39% over 3- to 22-year follow-up.
The markers of increased risk are:

x Shortest pre-excited RR interval <250 ms during spontaneous or induced
AF.
x A history of symptomatic tachycardia.
x The presence of multiple APs.
x Ebstein’s anomaly.
Since the efficacy of catheter ablation of APs is 95%, this is the management of
choice for patients with evidence pre-excitation and AF.16 Patients who have
survived SCD in the presence of an overt AP should have urgent AP ablation.
Successful catheter ablation in those patients eliminates the risk for SCD.
Patients with overt pre-excitation and high risk of AF, or patients with high-risk
professions such as public transport vehicle drivers, pilots, or competitive
athletes should be considered for ablation.
The indication for catheter ablation of an overt AP in an asymptomatic patient is

still controversial (especially in children).165 Most patients with asymptomatic pre-
excitation have a good prognosis; SCD is rarely the rst manifestation of the
disease.
The positive predictive value of invasive electrophysiological testing is

considered to be too low to justify routine use in asymptomatic patients. Catheter
ablation of an asymptomatic overt AP should remain a case-by-case decision
with detailed counseling of the patient (and family) about the natural course and
the risk of SCD versus the risk of an ablation procedure.
Catheter
Keypointsablation of an overt AP in patients with AF is recommended to prevent
SCD.164
Catheter ablation of an overt AP in patients with AF is recommended to prevent
IA
IA 164
Immediate SCD.
referral to an experienced ablation centre for catheter ablation is
recommended for patients
Immediate referral who
to ansurvived SCD
experienced and have
ablation centreevidence of ablation
for catheter overt AP is
I CIC
conduction.recommended for patients who survived SCD and have evidence of overt AP
conduction.
Catheter ablation is recommended for patients with high-risk professions (e.g.
pilots, Catheter
public ablation
transport is recommended
drivers) and overt but forasymptomatic
patients with high-risk professions
AP conduction on(e.g.
the
I BIB pilots,
164 public transport drivers) and overt but asymptomatic AP conduction on the
surface ECG. 164
surface ECG.
Catheter ablation
Catheterisablation
recommended in patients
is recommended at high
in patients risk risk
at high of developing
of developingAF
AFininthe
the
I BIB
presence ofpresence
an overtofbut asymptomatic AP onAP theonsurface ECG. 166
an overt but asymptomatic the surface ECG.166
Asymptomatic
Asymptomatic
IIaB
IIa B patients
patients with with evidence
evidence of an of an overt
overt AP should
AP should be be considered for
considered for
166
catheter
catheter ablation ofablation
the APofonly
the AP only
after a after a full explanation
full explanation andand careful
careful counseling.166
counseling.
9.4 HYPERTHYROIDISM̘
AF occurs in 10% to 25% of patients with hyperthyroidism, more commonly in
AF occurs men
in 10% to 25%
and elderly of patients with hyperthyroidism, more commonly in
patients.
men and elderly patients.
Treatment is directed primarily toward restoring a euthyroid state, which is usually
associated with a spontaneous reversion to sinus rhythm.
Treatment is directed primarily toward restoring
60 a euthyroid state, which is usually
associated Antiarrhythmic
with a spontaneous reversion
drugs and to sinus
direct-current rhythm. are generally unsuccessful
cardioversion
164
surface
Asymptomatic ECG. with evidence of an overt AP should be considered for
patients
Ia B
catheter ablation of the AP only after a full explanation and careful counseling.166
Catheter ablation is recommended in patients at high risk of developing AF in the
IB
presence of an overt but asymptomatic AP on the surface ECG.166
IIa B Asymptomatic patients with evidence of an overt AP should be considered for
AF occurs catheter
in 10%ablation
to 25% of patients
of the witha full
AP only after hyperthyroidism, more counseling.
explanation and careful commonly166in
men and elderly patients.
Treatment is directed primarily toward restoring a euthyroid state, which is usually
AF occurs in 10% to 25% of patients with hyperthyroidism, more commonly in
associated men
withand
a spontaneous reversion to sinus rhythm.
elderly patients.
Antiarrhythmic drugsisand
Treatment direct-current
directed cardioversion
primarily toward are generally
restoring a euthyroid unsuccessful
state, which is usually
while the thyrotoxicosis
associated withpersists.
a spontaneous reversion to sinus rhythm.
Antiarrhythmic
The occurrence drugs and direct-current
of hyperthyroidism following cardioversion
treatment withare generally
amiodarone unsuccessful
is often
while the thyrotoxicosis persists.
encountered in clinical practice. There are two types of amiodarone-induced
hyperthyroidism:
The occurrence of hyperthyroidism following treatment with amiodarone is often
x Type I, where there
encountered is an excess
in clinical practice.iodide-induced
There are two production of T4 and T3
types of amiodarone-induced
x Type hyperthyroidism:
II, where there is a destructive thyroiditis with a transient excess
x Type
release of T4 andI, where there later,
T3, and, is an excess
reducediodide-induced production of T4 and T3
thyroid function.
x Type II, where there is a destructive thyroiditis with a transient excess
release of T4 and T3, and, later, reduced thyroid function.
Although amiodarone may be continued when hypothyroidism has been
successfully treatedamiodarone
Although with replacement
may be therapy,
continued itwhen
is necessary to discontinue
hypothyroidism has been
amiodaronesuccessfully
if hyperthyroidism
treated withdevelops.
replacementThyrotoxicosis may alsoto occur
therapy, it is necessary after
discontinue
amiodarone if hyperthyroidism
cessation of amiodarone therapy. develops. Thyrotoxicosis may also occur after
cessation of amiodarone therapy.
Keypoints
In patients Inwith active
patients withthyroid disease,
active thyroid antithrombotic
disease, therapy
antithrombotic therapyis isrecommended
recommended
IC IIC
C on the presence of other stroke risk factors.
based based on the presence of other stroke risk factors.
Administration
When a ȕ-blockerof a ȕ-blocker
Administration beis used,
recommended
of a ȕ-blocker
cannot is recommendedto control
administration of athenon-dihydropyridine
to control rate
the rateofofventricular
ventricular
II C
C IIC
C
calcium inresponse
responsechannelpatients inwith
patients
antagonist with AF complicating
AF (diltiazem
complicating thyrotoxicosis,
thyrotoxicosis,
or verapamil) unless
unless contraindicated.
contraindicated.
is recommended to control
the ventricular
Whenratea inȕ-blocker
patientscannot
with AFbeand thyrotoxicosis.
used, administration of a non-dihydropyridine
IC
IC
calcium channel antagonist (diltiazem or verapamil) is recommended to control
If a rhythmthe ventricular
control rate in patients
strategy with AF itand
is desirable, is thyrotoxicosis.
necessary to normalize thyroid
IC When a ȕ-blocker cannot be used,the administration of aremains
non-dihydropyridine
function prior to cardioversion, as otherwise risk of relapse high.
IC Ifcalcium
a rhythm control strategy is desirable,
channel antagonist (diltiazem or verapamil)it is necessary to normalize
is recommended to thyroid
control
IC
IC
function prior torate
cardioversion, as otherwise the risk of relapse remains high.
the ventricular in patients with AF and thyrotoxicosis.
IC Once a euthyroid state is restored, recommendations for antithrombotic
prophylaxis
IC
IC Ifare
Once the
a same
a rhythm as for
euthyroid
control patients
state
strategy without recommendations
is isrestored,
desirable, hyperthyroidism.
it is necessary tofor antithrombotic
normalize thyroid
IC prophylaxis are
function prior to the same as foras
cardioversion, patients without
otherwise hyperthyroidism.
the risk of relapse remains high.
Once a euthyroid state is restored, recommendations for antithrombotic

9.5.I CPREGNANCY
9.5. PREGNANCY
prophylaxis are the same as for patients without hyperthyroidism.
AF is rare AF
during pregnancy
is rare and usually
during pregnancy has an
and usually hasidentifiable underlying
an identifiable underlying cause,
cause,
such as: such as:
9.5. PREGNANCY
167 167
o MitralAF ois Mitral
stenosis, stenosis,
rare during pregnancy and usually has an identifiable underlying cause,
such
o as:
congenital heart disease,
168
168
or
o congenital heart disease, or
169
o hyperthyroidism.
o Mitral stenosis,
169
167
o hyperthyroidism.
A o
rapid ventricular
congenital response168 or
heart disease, to AF can have serious hemodynamic
A rapid ventricular
consequencesresponse
for both169 the to AF and
mother can the have serious
foetus. In hemodynamic
a pregnant woman who
consequences oforhyperthyroidism.
develops AF, diagnosis
both the mother and and
treatment of the underlying
the foetus. condition
In a pregnant causingwho
woman the
arrhythmia
develops AF, rapid are
A diagnosis the
andfirsttreatment
ventricular priorities.
response oftothe AFunderlying
can have condition causing the
serious hemodynamic
consequences
arrhythmia are for both the mother and the foetus. In a pregnant woman who
the first priorities.
IC Digoxin, a beta blocker, or non-dihydropyridine calcium channel antagonist is
develops AF, diagnosis and treatment of the underlying condition causing the
recommended
arrhythmia are to
thecontrol the ventricular rate in pregnant patients.170-172
first priorities.
C Keypoints
Digoxin, a beta blocker, or non-dihydropyridine calcium channel antagonist is
170-172
recommended to control
Propranolol
Digoxin, andthe
a beta ventricular
metoprolol
blocker, rate
orwould in pregnant
be the patients.
beta-blockers
non-dihydropyridine of channel
calcium choice, while atenolol
antagonist is
ICIC
is contraindicated. Atenolol given in the rst trimester, but not 170-172
later, has been
recommended to control the ventricular rate in pregnant patients.
Propranololassociated
and metoprololwith foetal
wouldgrowth retardation.
be the Use ofofbeta-blockers
beta-blockers choice, while in atenolol
the first
trimester
Propranololis toand
be metoprolol
preferably avoided.
would
is contraindicated. Atenolol given in the be thetrimester,
rst beta-blockers
butofnot
choice, while
later, hasatenolol
been
iswith
associated All contraindicated. Atenolol
foetal available
growth given in the
retardation. rst of
Use trimester, but not later,
beta-blockers has been
in cross
the first
currently
associated with foetal antiarrhythmic drugs
growth retardation. have
Use ofthe potential to
beta-blockers the
in the first
trimester is placenta
to be preferably
trimester and
is toenter avoided.
breast milk
be preferably and should therefore be avoided if possible.
avoided.
171 173 173
All currently currently sotalol,
Quinidine,
All available available and flecainide
antiarrhythmic 61
antiarrhythmic havehave
drugs drugs
have all been
the used successfully
potential
the potential totocross for
cross the
the
placenta andpharmacological
enter breast
placenta and entercardioversion
milk andmilk
breast during
should
and pregnancy,
therefore
should however,
be avoided
therefore if in
be avoided relatively small
possible.
if possible.
numbers of cases.
IC Digoxin, a beta blocker, or non-dihydropyridine calcium channel antagonist is
recommended to control the ventricular rate in pregnant patients.170-172
Propranolol and metoprolol would be the beta-blockers of choice, while atenolol

is contraindicated. Atenolol given in the rst trimester, but not later, has been
associated with foetal growth retardation. Use of beta-blockers in the first
trimester is to be preferably avoided.
All currently available antiarrhythmic drugs have the potential to cross the
placenta and enter breast milk and should therefore be avoided if possible.
Quinidine,171 sotalol,173 and flecainide173 have all been used successfully for
pharmacological cardioversion during pregnancy, however, in relatively small
numbers of cases.
DCCV can be performed safely at all stages of pregnancy, and is recommended
IIbC Quinidine (has the longest record of safety in pregnancy) or procainamide may
inIIbC
patients who are haemodynamically
be considered unstable
for pharmacological due to AF,
cardioversion in and whenever the
hemodynamically risk
stable
of ongoingpatients
AF iswho considered
develop AFhigh,
during for the mother
pregnancy. 171,174 or for the foetus. Foetal
monitoring should be done during and following the DCCV.
DCCV can be performed safely at all stages of pregnancy, and is recommended
I CIC in patients who are haemodynamically unstable due to AF, and whenever the risk
of ongoing AF is considered high, for the mother or for the foetus. Foetal
The role ofmonitoring
anticoagulation to prevent systemic arterial embolism has not been
should be done during and following the DCCV.
systematically studied in pregnant patients with AF, but the arrhythmia is
frequently associated with conditions that carry a high risk of thromboembolism,
including congenital
The role oforanticoagulation
valvular heart to disease.
prevent systemic arterial embolism has not been
systematically studied in pregnant patients with AF, but the arrhythmia is
frequentlythromboembolism
Protection against associated with conditions that carry a high
is recommended risk of thromboembolism,
throughout pregnancy for
including congenital or valvular heart disease.
patients with AF except those at low thromboembolic risk. The choice of
anticoagulant or aspirin
Protection should
against be chosen according
thromboembolism to the throughout
is recommended stage of pregnancy.
pregnancy for
ICIC
patients with AF except those at low thromboembolic risk. The choice of
Consideration should or
anticoagulant beaspirin
givenshould
to avoiding
be chosen warfarin because
according to the stageitof crosses
pregnancy.the
placental barrier and is associated with teratogenic embryopathy in the first
Consideration
trimester and with foetal haemorrhage in the later stages of pregnancy.crosses
should be given to avoiding warfarin because it 172-179 the
placental barrier and is associated with teratogenic embryopathy in the first
trimester and with foetal haemorrhage in the later stages of pregnancy. 172-179
Heparin is the preferred anticoagulant because it does not cross the placenta.
Heparin is the preferred anticoagulant because it does not cross the placenta.
Subcutaneous administration of LMWH in weight-adjusted therapeutic doses is
recommended Subcutaneous
during theadministration
rst trimester of and
LMWHtheinlast
weight-adjusted therapeutic doses is
month of pregnancy.
recommended
Alternatively,
I BIB UFH may during the rst
be given, to trimester
prolongand
thethe last month
activated of pregnancy.
partial thromboplastin
Alternatively, UFH may180 be given, to prolong the activated partial thromboplastin
time to 1.5 time
timesto the control.
1.5 times the control.180
During
IIbC the second
IIbC trimester,
During the consider
second trimester, oral anticoagulation
consider for for
oral anticoagulation pregnant
pregnantwomen
women
180
with AF
with AF at high risk.180risk.
at high thromboembolic
thromboembolic
The following are guiding principles for the use of drugs in pregnancy:
The following are guiding principles for the use of drugs in pregnancy:
o Frequent monitoring with ECG and drug levels is recommended to reduce
o Frequent monitoring with ECG and drug levels is recommended to reduce
the risk of toxicity.
the riskoof Iftoxicity.
possible, start after 8 weeks of pregnancy or as late as possible.
o If possible,
o Use start aftereffective
lowest 8 weeks of pregnancy or as late as possible.
dose.
o Use lowesto Low dose combination
effective dose. therapy preferable to higher dose single drug
o Low dose therapy.
combination therapy preferable to higher dose single drug
o Use older agents with longest tract record.
therapy.
o Use older agents with longest tract record.
9.6 HYPERTROPHIC CARDIOMYOPATHY̘
Patients with hypertrophic cardiomyopathy (HCM) are at greater risk of

9.6 HYPERTROPHIC CARDIOMYOPATHY̘
developing AF compared with the general population, and around 20 – 25%
develop AF with an annual incidence of 2%.
Patients with hypertrophic cardiomyopathy (HCM) are at greater risk of
developing AF compared with the general population, and around 20 – 25%
develop AF with an annual incidence of 2%.
62
AF is the major determinant of hemodynamic deterioration in patients with HCM
AF is
and the majorcan
symptoms determinant
be ameliorated of hemodynamic
by restoration deterioration
of sinus rhythm.in patients with HCM
and symptoms can be ameliorated by restoration of sinus rhythm.
Amiodarone may be the most effective agent for reducing the occurrence of
AmiodaroneAF
paroxysmal mayandbe for the most effective
preventing recurrence. agent for reducing the occurrence of
paroxysmal AF and for preventing recurrence.
AF is the major determinant of hemodynamic deterioration in patients with HCM
In chronic and AF,symptoms
rate control can usually
can be ameliorated be achieved
by restoration of sinuswith
rhythm.ß-blockers and
In chronicAV
verapamil. AF, nodalrateablation
controlwith canpermanent
usually be achievedpacing
ventricular with (to ß-blockers
promote late and
verapamil. AV nodal
Amiodarone ablation
may be with
septal activation) may be helpful in selected patients.
the permanent
most effective ventricular
agent for pacing
reducing (to occurrence
the promote late of
septal activation)
paroxysmal mayAF beandhelpful in selected
for preventing patients.
recurrence.
Unless contraindicated, OAC therapy should be administered to patients with
Unless In chronic AF, OAC rate control can usuallybebeadministered
achieved with ß-blockers with and
HCM andcontraindicated,
paroxysmal,
verapamil. AVpersistent,
therapy
nodal ablation
should
or permanent
with permanent AF.ventricular pacingto(topatients promote late
HCM and paroxysmal, persistent, or permanent AF.
septal activation) may be helpful in selected patients.
Outcomes after AF ablation in patients with HCM are favourable, but not as
Outcomes Unless
successful afterin AF
as ablation populations.
unselected
contraindicated, in OAC
patients
therapywith HCMbeare
LAshould
ablation isfavourable,
signicantly
administered but notwith
better
to patients as
in
successful HCM
paroxysmal as
AF in and unselected
than paroxysmal,
in persistent populations.
persistent,
AF. or LA ablation
In permanent
addition, AF. is signicantly
patients with marked better
atrialin
paroxysmal AF
enlargement and than
severe in diastolic
persistent AF. In addition,
dysfunction are at high patients
risk ofwith marked atrial
recurrence.
Outcomes after AF ablation in patients
enlargement and severe diastolic dysfunction are at high risk of recurrence.with HCM are favourable, but not as
successful as in unselected populations. LA ablation is signicantly better in
The small series paroxysmal of surgical
AF than ablation
in persistent (Maze-III procedure)
AF. In addition, in combination
patients with marked atrialwith
The small enlargement
myomectomy series
whenofLV surgical
andoutflow
severe ablation
tract (Maze-III
obstruction
diastolic dysfunctionwasprocedure)
are atpresent,
high riskinforcombination
of AF in patients
recurrence. with
myomectomy
with HCM showed whenno LVincrease
outflow tract obstruction
in operative was present,
mortality and a high for AF in patients
proportion of
with HCM
patients showed
The
remained smallin no
seriesincrease
sinus of surgical
rhythm in operative
ablation mortality
over a(Maze-III
mean and a high
procedure)
follow-up 15proportion
in combination
of months. withof
181
myomectomy when LV outflow over
tract obstruction was present,offor15 AFmonths. 181
in patients
patients remained in sinus rhythm a
Despite conicting data, there seems to be an overall benecial effect of mean follow-up
with HCM showed
Despite conicting data,the no increase
there seems in operative mortality
overallandbenecial
a high proportion
effect of
myomectomy in reducing
patients remained inburden of AFtoinover
sinus rhythm
be an
HCM patients.
a mean follow-up of 15 months.181
of
myomectomy in reducing the burden of AF in HCM patients.
Despite conicting data, there seems to be an overall benecial effect of
Restorationmyomectomy
of sinus rhythm in reducing bytheDCCV
burden of orAFpharmacological
in HCM patients. cardioversion is
Keypoints
Restoration ofinsinus rhythm by DCCV or pharmacological
B recommended patients with HCM presenting with recent-onset cardioversion
AF.182 182
is
IB recommended in patients
Restoration with HCM
of sinus rhythmpresenting
by DCCV with recent-onset AF.
or pharmacological cardioversion is
IBIB therapy recommended in patients with HCM presenting with recent-onset AF.182
OAC (INR 2.0–3.0) is recommended in patients with HCM who develop
B OAC
AF therapy
unless (INR 2.0–3.0)
contraindicated. 182is recommended in patients with HCM who develop
IB OAC therapy (INR182 2.0–3.0) is recommended in patients with HCM who develop
AF
IBIBunless contraindicated.
AF unless contraindicated.182
Ia C
Amiodarone should be considered in order to achieve rhythm control and to
IIa C
Amiodarone
maintain sinus should
rhythmbe
Amiodarone in considered
patients
should withinHCM.
be considered order to achieve
in order to achieve rhythm
rhythmcontrol
control and
and to to
IIaC
IIa C
maintain sinus rhythm
maintain sinusinrhythm
patients with HCM.
in patients with HCM.
Catheter ablation of AF should be considered in patients with symptomatic AF
Ia C Catheter Catheter of
ablation ablation
AF should of AF should be considered
be considered in patients
in patients withwithsymptomatic
symptomatic AF AF
IIa C
refractory
IIaC
IIa C torefractory
pharmacological control.
to pharmacological control.
refractory to pharmacological control.
Ia C Ablation
IIaC
IIa C procedures (with concomitant
Ablation procedures (with concomitantseptalseptal
myomectomy
myomectomy if indicated)
if indicated)may may bebe
IIa C Ablation
considered procedures
in patientsin
considered (with
with concomitant
HCM
patients withand HCM septal
refractory
and myomectomy
AF. AF.
refractory if indicated) may be
considered in patients with HCM and refractory AF.
9.7 PULMONARY DISEASES̘
Supraventricular arrhythmias, including AF, are common in patients with COPD
Supraventricular arrhythmias,
and have including
adverse prognostic AF, areincommon
implications in patients
patients with with COPD
acute exacerbations of
Supraventricular
and COPD. arrhythmias,
have adverse including AF,
prognostic implications are common
in patients in patients
with acute with COPD
exacerbations of
and have adverse prognostic implications in patients with acute exacerbations of
COPD.
COPD.
Keypoints
For patients who develop AF during an acute pulmonary illness or exacerbation
IC
IC of chronic pulmonary disease, treatment of the underlying lung disease and
correction of hypoxemia and acidosis are the primary therapeutic measures.
IIIC
IIIC Theophylline and beta-adrenergic agonist agents are not recommended in
patients with bronchospastic lung disease who develop AF.
Beta-blockers, sotalol, propafenone, and adenosine are contraindicated in

IIIC
IIIC patients with bronchospasm.
Diltiazem or verapamil is recommended

63 to control the ventricular rate in patients
IC
with obstructive pulmonary disease who develop AF with or without digoxin.
IC of chronic pulmonary disease, treatment of the underlying lung disease and
correction of hypoxemia and acidosis are the primary therapeutic measures.
Beta-blockers,
IIIC sotalol,and
Theophylline propafenone, andagonist
beta-adrenergic adenosine
agents are contraindicated
are not recommended in
in
patients with bronchospasm.
Diltiazem Beta-blockers,
or verapamil issotalol, propafenone,
recommended and adenosine
to control are contraindicated
the ventricular in
rate in patients
IIIC patients with bronchospasm.
with obstructive pulmonary disease who develop AF with or without digoxin.
Diltiazem or verapamil is recommended to control the ventricular rate in patients
ICICselective blockers (e.g. bisoprolol) in small doses should be considered as an
ȕ-1 with obstructive pulmonary disease who develop AF with or without digoxin.
alternative for ventricular rate control.
ȕ-1 selective blockers (e.g. bisoprolol) in small doses should be considered as an
IIaC
IIa C alternative for ineffective
ventricular rate control.AF unless respiratory decompensation
Cardioversion may be against
has been corrected.
Cardioversion may be ineffective against AF unless respiratory decompensation
has been corrected.
Direct-current cardioversion should be attempted in patients with pulmonary
disease who become hemodynamically
Direct-current unstable
cardioversion should as a consequence
be attempted of AF.
in patients with pulmonary
ICIC disease who become hemodynamically unstable as a consequence of AF.
In patients refractory to drug therapy, AV nodal ablation and ventricular pacing
In patients
may be necessary to refractory
control theto drug therapy,rate.
ventricular AV nodal ablation and ventricular pacing
may be necessary to control the ventricular rate.
In patientsInwith AF and
patients pulmonary
with AF disease,
and pulmonary the general
disease, recommendations
the general recommendations for
for
antithrombotic therapy apply.
antithrombotic therapy apply.
9.8 HEART9.8 HEART FAILURE

FAILURE
AF is a strong and independent risk factor for the development of heart failure,
AF is a strong and conditions
and both independent risk factor
frequently for17,183
co-exist. theThe
development
onset of AFof
in heart failure,
a patient with
17,183
and both conditions
heart failure frequently
often leads toco-exist. The onset of
symptomatic deterioration, AF in a topatient
predisposes episodeswith
of
heart failure often leads
worsening hearttofailure,
symptomatic
increasesdeterioration, predisposes toepisodes,
the risk of thrombo-embolic episodesandof
worsening worsens
heart failure,
long-term increases
outcome. the risk of thrombo-embolic episodes, and
worsens long-term outcome.
In the initial approach to heart failure patients with AF, the following issues need
to be considered:17
In the initial approach to heart failure patients with AF, the following issues need
17
to be considered:x Potential precipitating factors and secondary causes should be identied
and if possible corrected.
x Potential
x precipitating
Background heartfactors
failureand secondary
treatment shouldcauses should be identied
be optimized.
and if possible corrected.
x Background heart failure treatment should be optimized. failure and AF, ß-
When ventricular rate control is required in patients with heart
When ventricular rate control is required in patients with heart failure and AF, ß-
blockers are preferred over digitalis glycosides due to their rate-controlling effect
during exertion rather than only at rest. A combination of digoxin and a ß-blocker
may be more effective than a single drug for heart-rate control at rest. Therapy
with ß-blockers alone or in combination with digoxin was associated with lower
mortality rates compared with treatment with digoxin alone.184
ß-Blockers have favourable effects on mortality and morbidity in patients with

systolic heart failure. A recent meta-analysis also showed a 27% reduction in the
incidence of new-onset AF in patients with systolic heart failure treated with ß-
blockers.185
Although diltiazem effectively controls excessive heart rate during exercise, it

adversely suppresses myocardial contraction and increases the risk of heart
failure. For patients with heart failure and preserved ejection fraction, these drugs
used in combination with digoxin appear to be more effective in controlling heart
rate over 24 h and during exercise than digoxin or non-dihydropyridine calcium
channel antagonist monotherapy.
The rhythm control strategy has not been shown to be superior to rate control in
heart failure patients with AF.27 Catheter-based LA ablation procedures in heart
failure patients may lead to improvement in LV function, exercise tolerance, and
quality of life in selected patients (see Section 8.3.1).29,30
64
The prevention of thrombo-embolism is covered in Section 6, but the presence of
heart failure due to systolic dysfunction is itself a risk factor for stroke and
Although
rate over 24 h anddiltiazem effectively than
during exercise controls excessive
digoxin heart rate during exercise,
or non-dihydropyridine calciumit
adversely monotherapy.
channel antagonist suppresses myocardial contraction and increases the risk of heart
failure. For patients with heart failure and preserved ejection fraction, these drugs
used in combination with digoxin appear to be more effective in controlling heart
The rhythmrate control strategy
over 24 has not
h and during been than
exercise shown to be
digoxin or superior to rate control
non-dihydropyridine calcium in
27
heart failure patients
channel with AF.
antagonist Catheter-based LA ablation procedures in heart
monotherapy.
Theinrhythm
quality of life control
selected strategy
patients hasSection
(see shown29,30
not been8.3.1). to be superior to rate control in
27
heart failure patients with AF. Catheter-based LA ablation procedures in heart
The prevention of thrombo-embolism is covered in Section 6, but the presence of
quality of life in selected patients (see Section 8.3.1).29,30
thrombo-embolism, and of
The prevention OAC therapy is generally
thrombo-embolism indicated
is covered in Section when
6, butAF
theispresence
present.of
The use ofthrombo-embolism, and OAC therapy
aspirin is not recommended dueis generally indicated when
to the increased risk AF
of is present. in
bleeding
combination with OAC therapy and some evidence that aspirin may increase the
The use of aspirin is not recommended due to the increased risk of bleeding in
risk of hospitalizations for heart failure.
combination with OAC therapy and some evidence that aspirin may increase the
risk of hospitalizations for heart failure.
Keypoints
IC DCCV is recommended when a rapid ventricular rate does not respond to
DCCV ismeasures
pharmacological
I CIC recommended
in when a rapid
patients withventricular
AF and rate ongoing
does not myocardial
respond to
ischaemia,pharmacological measures inorpatients
symptomatic hypotension, symptoms withofAF and ongoing
pulmonary myocardial
congestion.
ischaemia, symptomatic hypotension, or symptoms of pulmonary congestion.
In patientsInwith AF with
patients and AF severe (NYHA(NYHA
and severe classclass
III or
III IV) or orrecent
or IV) recent (<4
(<4 weeks)
weeks)
IC unstable
I CIC heart failure,
unstable heartthe use the
failure, of antiarrhythmic therapy
use of antiarrhythmic therapyto maintain
to maintainsinus
sinus rhythm
rhythm
should be restricted to amiodarone.
should be restricted to amiodarone.
Administration
Administration of amiodarone
of amiodarone is a isreasonable
a reasonable optionforforpharmacological
option pharmacological
IIaB
IIa B cardioversion of AF, or to facilitate electrical cardioversion of AF. 21,39,45,186
IIa B cardioversion of AF, or to facilitate electrical cardioversion of AF.21,39,45,186
In patients with AF and stable heart failure (NYHA class I, II) dronedarone should
IIaC
InIIa C
patients with
be AF and to
considered stable
reduce heart failure (NYHA
cardiovascular class I, II) dronedarone should
hospitalizations.
IIa C For patients with heart failure and symptomatic persistent AF despite adequate
IIb B be considered to reduce cardiovascular hospitalizations.
rate control, electrical
For patients with heart cardioversion and rhythm
failure and symptomatic persistent control
AF despitemay be
adequate
IIbB
IIb B
considered. 27,29,30,32,187
rate control, electrical cardioversion and rhythm control may be
27,29,30,32,187
considered.
Catheter ablation (pulmonary vein isolation) may be considered in heart failure
IIb B Catheter ablation (pulmonary vein29,30
isolation) may be considered in heart failure
patients
IIbB
IIb B with refractory
patients symptomatic
with refractory AF. AF.29,30
symptomatic
9.9 ATHLETES
9.9 ATHLETES
In population-based studies, the intensity of physical activity showed a U-shaped

In population-based studies, the intensity of physical activity showed a U-shaped
relationship with incident AF, which may indicate that the positive antiarrhythmic
relationshipeffects
with incident
of physicalAF, which
activity may
are indicate
partially that the positive
negated antiarrhythmic
when exercise is too
effects of strenuous.
physical188,189
activity
AF is 2 are partially
– 10 times negated in when
more prevalent active orexercise is too
former competitive
188,189
strenuous. athletes AFandis 2those
– 10performing
times more prevalent
intense in active
recreational or former
endurance competitive
sports. 190,191
The
190,191
athletes and thoseforperforming
reasons intense
this association recreational
are probably endurance
both functional sports.sympathetic
(increased The
reasons foractivity, volume loadare
this association during exercise,
probably bothvagotonia
functionalat rest) and structural
(increased sympathetic (atrial
hypertrophy and dilatation).
activity, volume load during exercise, vagotonia at rest) and structural (atrial
hypertrophyRateandcontrol
dilatation).
is difficult to achieve in athletes. ß-blockers are not well tolerated
and may even be prohibited in some competitive sports, and digoxin or non-
Rate control is difficult tocalcium
dihydropyridine achieve in athletes.
antagonists will notß-blockers are not
be potent enough well heart
to slow tolerated
rate
and may even
duringbe prohibited
exertional AF. in some competitive sports, and digoxin or non-
dihydropyridine calcium antagonists will not be potent enough to slow heart rate
When the heart rate during AF is acceptable at maximal physical performance for
during exertional AF.
a given athlete without signs of haemodynamic impairment (dizziness, syncope,
sudden fatigue), competitive sports activity can be resumed.
When the heart rate during AF is acceptable at maximal physical performance for
a given athlete without
Caution signs when
is necessary of haemodynamic
using flecainide impairment
and propafenone(dizziness, syncope,
as monotherapy in
sudden fatigue),
athletes with AF.192 These
competitive sportsdrugs
activity
maycan
leadbe
to resumed.
atrial utter, with 1 to 1 conduction
to the ventricles during high sympathetic tone. Therefore, ablation of the utter
circuit may be needed in athletes with documented atrial utter. Continuation of
Caution is necessary when using flecainide and propafenone as monotherapy in
drug therapy for AF will often be required despite successful ablation (‘hybrid
athletes with AF.192 These drugs may lead to atrial utter, with 1 to 1 conduction
therapy’).
circuit mayInbesome
needed in with
athletes athletes with documented
paroxysmal AF, ecainide atrial utter. Continuation
or propafenone can be used for of
drug therapy
acuteforconversion
AF will often be required despite
(the ‘pill-in-the-pocket’ successful
approach; 5.1.2.1).42(‘hybrid
see Sectionablation These
therapy’). patients should refrain from sports as long as the atrial arrhythmia persists and
until one to two half-lives of the antiarrhythmic drug have elapsed.
65
In some athletes with paroxysmal
Non- pharmacological AF,such
options ecainide or ablation
as catheter propafenone
can be can be used
considered. 193 for
acute conversion (the ‘pill-in-the-pocket’ approach; see Section 5.1.2.1).42 These

Caution is necessary when using flecainide and propafenone as monotherapy in
athletes with AF.192 These drugs may lead to atrial utter, with 1 to 1 conduction
circuit may be needed in athletes with documented atrial utter. Continuation of
drug therapy for AF will often be required despite successful ablation (‘hybrid
therapy’).
In some athletes with paroxysmal AF, ecainide or propafenone can be used for
acute conversion (the ‘pill-in-the-pocket’ approach; see Section 5.1.2.1).42 These
patients should refrain from sports as long as the atrial arrhythmia persists and
until one to two half-lives of the antiarrhythmic drug have elapsed.
Non- pharmacological options such as catheter ablation can be considered. 193
Anticoagulation may be necessary depending on the presence of risk factors for

thrombo-embolic events (see Section 6.1). However, anticoagulation cannot be
used in individuals participating in sporting activities with a risk of bodily collision.
When a ‘pill-in-the-pocket’ approach with sodium channel blockers is used, sport
cessation
Keypointsshould be considered for as long as the arrhythmia persists, and until
1–2 half-lives of the antiarrhythmic drug used have elapsed.
When a ‘pill-in-the-pocket’ approach with sodium channel blockers is used, sport
IIaC
IIa C
cessation
Isthmus ablation should
should bebe consideredinforcompetitive
considered as long as the
or arrhythmia persists,
leisure-time athletesandwith
until
1–2 half-lives of the antiarrhythmic drug used have elapsed.
documented atrial utter, especially when therapy with ecainide or propafenone
is intended.Isthmus ablation should be considered in competitive or leisure-time athletes with
IIaC
IIa C
documented atrial utter, especially
When a ‘pill-in-the-pocket’ approachwhen therapychannel
with sodium with ecainide
blockersorispropafenone
used, sport
IIa C
Where appropriate,
iscessation
intended.AF ablation
should should be
be considered for considered
as long as thetoarrhythmia
prevent recurrent AFuntil
persists, and in
athletes. 1–2 half-lives of the antiarrhythmic drug used have elapsed.
IIaC
IIa C Where appropriate, AF ablation should be considered to prevent recurrent AF in
athletes.
Isthmus ablation should be considered in competitive or leisure-time athletes with
WhenIIa C a specic cause for AF is identied in an athlete (such as
documented atrial utter, especially when therapy with ecainide or propafenone
hyperthyroidism), ita isspecic
is intended.
When not recommended
cause for AF to continue participation
is identied in competitive
in an athlete (such as
or IIIC
III C
leisure time sports until correction
hyperthyroidism), of the cause.
it is not recommended to continue participation in competitive
IIa C orWhere
leisureappropriate,
time sportsAF ablation
until should
correction be cause.
of the considered to prevent recurrent AF in
athletes.
It is not recommended to allow physical sports activity when symptoms due to
haemodynamic
IIIC
III C
It is not recommended
impairment (suchtoas
allow physical are
dizziness) sports activity when symptoms due to
present.
When a specic
haemodynamic cause(such
impairment for asAFdizziness)
is identied in an athlete (such as
are present.
III C
hyperthyroidism), it is not recommended to continue participation in competitive
or leisure time sports until correction of the cause.
9.10 VALVULAR HEART DISEASE
9.10 VALVULAR HEART DISEASE
III C
It is not recommended to allow physical sports activity when symptoms due to
AF frequentlyhaemodynamic
accompanies
AF frequently impairment
valvular
accompanies (such as dizziness)
heart
valvular disease.
heart areLA
disease. present.
distension
LA distension is isananearly
early
manifestation
manifestation of progressive
of progressive mitral mitral
valve valve
disease, disease,
andand thethepresence
presence of of
paroxysmal
paroxysmal or permanent or permanent
AF AF is
is anDISEASE an accepted indication for early
accepted indication for early percutaneous or percutaneous or
9.10 VALVULAR HEART
surgical mitral intervention. 66
AF is also frequently seen in later stages of aortic
surgical mitral intervention.66 AF is also frequently seen in later stages of aortic
valve disease when LV dilatation and elevated end-diastolic pressure exert
valve diseaseAF when LV
frequently dilatation
accompanies
secondary effects on LA function. and elevated
valvular end-diastolic
heart disease. pressure
LA distension is anexert
early
manifestation
secondary effects of progressive mitral valve disease, and the presence of
on LA function.
paroxysmal orofpermanent
Management AF followsAF conventional
is an acceptedrecommendations
indication for earlyinpercutaneous
the setting or of
66
surgical heart
mitral disease,
intervention. AF isaalso
ratefrequently
control seen in later stages of aortic
Management of AF
valvular
valve
follows
disease when
conventional
LV
although
dilatation
recommendations
and elevated
strategy inis the
end-diastolic
setting
usually
pressure
of
adopted
exert
because
valvular heart of the low
disease, likelihoodaofrate
although maintaining
controlsinus rhythm in
strategy is the long term.
usually adopted
secondary effects on LA function.
because of the low likelihood of maintaining sinus rhythm in the long term.
Principal concerns surround the high risk of thrombo-embolism in subjects with
Management of AF follows conventional recommendations in the setting of
valvular heart disease, and a low threshold for anticoagulation is recommended
valvular surround
Principal concerns heart disease, although a rate control strategy is usually adopted
(See Section 6.1). the high risk of thrombo-embolism in subjects with
valvular heartbecause of the
disease, andlowa likelihood of maintaining
low threshold sinus rhythm inisthe
for anticoagulation long term.
recommended
(See SectionPrincipal
6.1). concerns surround the high risk of thrombo-embolism in subjects with
OAC therapy (INR 2.0–3.0) is indicated in patients with mitral stenosis and AF
IC valvular heartpersistent,
(paroxysmal, disease, and a low threshold for anticoagulation is recommended
or permanent).
(See Section 6.1).
Keypoints
OAC therapy (INR 2.0–3.0) is recommended in patients with AF and clinically
(paroxysmal,
IC persistent,
signicant mitralorregurgitation.
permanent).
I CIC (paroxysmal, persistent, or permanent).
OAC therapy (INR 2.0–3.0)
Percutaneous mitral is recommended
balloon in patients
valvotomy should with AFforand
be considered clinically
asymptomatic
IIa C
signicant mitral
OAC regurgitation.
patients with moderate
therapy or severe
(INR 2.0–3.0) mitral stenosisinand
is recommended suitable
patients valve
with AF anatomy who
and clinically
I CIC
have new-onset
signicant mitralAF in the absence of LA thrombus.
regurgitation.
Percutaneous mitral balloon valvotomy should be considered for asymptomatic
patients withPercutaneous
moderate ormitral balloon
severe valvotomy
mitral stenosis should be considered
and suitable valveforanatomy
asymptomatic
who
IIa C
patients with moderate or severe66mitral stenosis and suitable valve anatomy who
have new-onset AF in the absence of LA thrombus.
valvular heart disease, and a low threshold for anticoagulation is recommended
(See Section 6.1).
IC (paroxysmal, persistent, or permanent).
IC
OAC therapy (INR 2.0–3.0) is recommended in patients with AF and clinically
signicant mitral regurgitation.
Percutaneous mitral balloon valvotomy should be considered for asymptomatic

IIaC
IIa C
patients with moderate or severe mitral stenosis and suitable valve anatomy who
Early mitral valve surgery should be considered in severe mitral regurgitation,

IIaC
IIa C
preserved LV function, and new-onset AF, even in the absence of symptoms,
particularly when valve repair is feasible.
10. REFERRALS
10.1 Acute hospitalisation/referral

This is required for patients with:
x AF/AFL with haemodynamic compromise, acute dyspnoea, acute heart
failure, chest pain, ischaemia, near syncope, hypotension
x AF/AFL with rapid uncontrolled heart rate, e.g., over 140 bpm at rest
x AF/AFL with acute systemic illness requiring acute management
x rst/new onset of AF/AFL symptoms, no contraindications to cardioversion,
with the possibility of cardioversion within 48 hours of onset.
10.2 Outpatient specialist physician/cardiologist

Outpatient specialist referral is recommended for those who:
x Need further investigation/echocardiography
x Have suspected structural heart disease (e.g., hypertensive, valvular,
ischaemic)
x Are to be considered for cardioversion
x Are highly symptomatic, requiring ‘maintenance of sinus rhythm’
antiarrhythmic therapy
x Are having difficulty with pharmacological rate control
x Require a second opinion of the risk/benet ratio of anticoagulation
x Are having syncopal attacks.
10.3 Cardiac electrophysiologist (heart-rhythm specialist)

Tertiary referral is recommended for patients who have:
x AF with WPW syndrome (pre-excited AF)
x Highly-symptomatic AF unresponsive to rst-line antiarrhythmic treatment
x Uncontrolled ventricular rate with maximally tolerated atrioventricular-
blocking therapy
x Recurrent AFL (including mixed AFL and AF where AFL is the dominant
arrhythmia)
x Tachycardia-bradycardia syndrome (sinus node dysfunction)
x Suspicion or documentation of a regular tachycardia triggering AF (e.g.,
SVT).
10.4 No referral
Referral is not needed for patients who have rate-controlled AF with mild or
occasional symptoms, for whom echocardiography is not required (e.g.,
previously obtained), and for whom the decision regarding stroke prevention
management is clear cut.
67
11. AUDIT & EVALUATION
The Table below lists the audit criteria identified to evaluate the impact of the
implementation of the six key priority areas detailed above on clinical practice
and health outcomes.
Criterion Exception Definition of terms

All people presenting to None. Percentage of patient
primary or secondary records with a new
care with a history of diagnosis of AF made
hypertension, heart following an ECG made
failure, diabetes or stroke on the basis of detection
and noted to have an of an irregular pulse.
irregular pulse to be
offered an ECG and any
new diagnosis of AF
recorded.
All patients should be Haemodynamically Percentage of patient

assessed for risk of unstable patients or records with a
stroke/ thromboembolism those in whom documentation of risk
and given assessment is impossible assessment and
thromboprophylaxis or inappropriate. thromboprophylaxis
according to the stroke consistent with the stroke
risk stratification risk stratification
algorithms and have this algorithm.
assessment and any
antithrombotic therapy
recorded.
All patients should be Haemodynamically Percentage of patient
assessed for risk of unstable patients or records with a
bleeding and according those in whom documentation of risk
to the bleeding risk assessment is impossible assessment for bleeding
stratification algorithms or inappropriate. consistent with the
and have this bleeding risk stratification
assessment recorded. algorithm.
All AF patients in whom a Postoperative or Percentage of patient
rate-control or rhythm- haemodynamically records with a
control strategy is unstable patients, or documentation of
initiated to have their those otherwise not able involvement of the patient
involvement in choosing to engage in a decision- in the decision- making
a treatment strategy making process. process.
recorded.
All patients who are None. Percentage of patient
prescribed digoxin as records with a
initial monotherapy for prescription of digoxin for
68
rate control to have the initial rate-control
reason for this monotherapy where the
prescription recorded reason for digoxin
where it is not obvious prescription is:
(e.g. sedentary patient, • Sedentary patient
presence of • Presence of contra-
contraindication to indications to beta-
alternative agents). blockers
or rate-limiting calcium
Antagonists
• Other reasons.
All patients who are None. Percentage of patient

prescribed amiodarone records with a
as long-term therapy for prescription of
rhythm control to have amiodarone for long-term
the reason for this rhythm-control therapy
prescription recorded where the reason for
where it is not obvious amiodarone prescription
(e.g. failure of other is:
agents to control rhythm, • Presence of contra-
presence of indications to beta-
contraindication to blockers, dronedarone,
alternative agents). flecainide or propafenone
• Other reasons.
69
APPENDIX A
Search Terms
Scope of search
A literature search was conducted for guidelines, systematic reviews and
randomized controlled trials on the primary care management of Atrial
fibrillation, with additional searches in the following areas:
• Outpatient therapy
• Rhythm versus rate control
• Anti-arrhythmics for cardioversion
• Drugs for rate control
• Anticoagulation versus antiplatelet drugs to prevent thromboembolism
• Stroke risk versus bleeding risk
• Invasive or emerging therapies
• Referral criteria
Search dates
January 2010 –December 2011
Key search terms
Various combinations of searches were carried out. The terms listed below are
the core search terms that were used for Medline and these were adapted for
other databases.
• exp Atrial Fibrillation/, atrial fibrillation.tw

• exp Diagnosis/, exp Diagnosis, Differential/, exp Electrocardiography/,
exp Echocardiography/, exp Radiography, Thoracic/, exp Thyroid
Function Tests/, exp Hematologic Tests/, blood test$.tw
• exp atrial flutter.tw
• Outpatients/
• Ambulatory Care/
• (outpatient or out-patient).tw.
• exp Platelet Aggregation Inhibitors/, exp Aspirin/, exp Warfarin/
• exp thromboembolism/
• exp anticoagulants/
• $thromb$.ti,ab.
• anticoagul$.tw.
• exp Blood Coagulation/de, dt, pc [Drug Effects, Drug Therapy,
Prevention & Contro
• exp Platelet Aggregation Inhibitors/
• Aspirin/
• aspirin.tw.
• exp Anti-Arrhythmia Agents/, exp Calcium Channel Blockers/, exp
Verapamil/, exp Diltiazem/, exp Nifedipine/
• exp Adrenergic beta-Antagonists/, exp Atenolol/, exp Bisoprolol/,
exp Metoprolol/, exp Acebutolol/, exp Nadolol/, exp Oxprenolol/, exp
Propranolol/
70
• exp Digoxin/, exp Amiodarone/
• cardioversion/
• defibrillation/
• (countershock$ or (counter adj shock$)).tw. cardioconver$.tw.
• (electr$ adj3 (cardiover$ or conver$ or countershock)).tw. rhythm
control.tw.
• (electrover$ or (electric$ adj3 defibrillat$)).tw
• (antiarrhythm$ or anti-arrhythm$).tw.
• (pharmacol$ adj3 (cardiover$ or conver$ or cardioconver$)).tw.
• exp heart rate/
• (heart or cardiac or ventricular) adj3 rate).tw.
• (rate adj3 (control$ or reduc$ or normal$)).tw.
• (chronotrop$ adj3 therapy).tw.
• Digoxin/
• Verapamil/
• Diltiazem/
• (beta$ adj block$).tw.
• exp Beta Adrenergic Receptor Blocking Agent/
• Amiodarone/
• Clonidine/
• (ventricular adj5 pac$).
• exp thromboembolism/
• exp anticoagulants/
• $thromb$.ti,ab.
• anticoagul$.tw.
• exp Blood Coagulation/de, dt, pc [Drug Effects, Drug Therapy,
Prevention & Control
• exp Platelet Aggregation Inhibitors/
• Aspirin/
• aspirin.tw.
• exp Stroke/
• exp Hemorrhage/
• (heart or ventricular) adj3 rate).tw.
• *Heart Rate/de [Drug Effects]
• rate control.tw.
• (Cox or Maze).tw.
• (internal adj3 (defibrill$ or cardiover$)).tw.
• (radio$ or microwave$).tw.
• (cryotherm$ or cryoablat$).tw.
• laser$.tw.
• (atrial adj3 pac$).tw.
• (dual adj3 pac$).tw.
• (implant$ adj3 pacemaker$).tw.
• (AV nod$ adj3 ablat$).tw.
• (implant$ adj3 defibrill$).tw.
• (surg$ or catheter$) adj3 ablat$).tw.
• surgery/ or thoracic surgery/
• defibrillators, implantable/ or implants, experimental/
• exp Pulmonary Veins/ pulmonary vein$.tw
• exp Catheter Ablation/ or radiofrequency ablation.tw
• exp Catheter Ablation or radiofrequency catheter ablation.tw
71
APPENDIX B
Clinical questions
A. Introduction
1. What is the best way to classify atrial fibrillation?
2. What is the epidemiological characteristic of atrial fibrillation?
B. Initial management
1. What are the frequencies of the presenting symptoms?
2. In patients with suspected AF based on an irregular pulse, how accurate
is an ECG in diagnosing AF?
3. Should echocardiography be performed to identify underlying structural
heart disease?
4. In patients with suspected intermittent AF, how effective is ambulatory
ECG compared to an event ECG in diagnosing AF?
5. Which patients with AF would benefit from referral to specialist?
C. Management principles
1. In which patients with persistent AF does rate control result in improved
mortality/morbidity/quality of life over rhythm control?
2. In which patients with persistent AF does rhythm control result in
improved mortality/morbidity/quality of life over rate control?
D. Acute-onset AF
1. In haemodynamically unstable patients presenting with acute AF, what
is the best treatment strategy?
2. In which patients should pill-in-the-pocket therapy be recommended?
3. Does electrical cardioversion versus pharmacological cardioversion
affect rates of thromboembolism, quality of life, success rates?
4. In patients with persistent AF, is amiodarone better than a) flecainide or
b) propafenone for use in cardioversion?
5. In patients with persistent AF is amiodarone better than sotalol for use
in cardioversion?
6. What is the safety and efficacy of the adjunctive administration of
antiarrhythmic drugs for use in electrical cardioversion in comparison to
electrical cardioversion without adjunctive antiarrhythmic drugs?
7. Is a conventional anticoagulation strategy for elective cardioversion as
effective as a transoesophageal echocardiogram plus anticoagulation?
E. Prevention of thromboembolism
1. In patients with AF, what are the risk factors associated with stroke/TIA
and thromboembolism?
2. What is the efficacy of anticoagulation therapy versus placebo for
stroke prevention in: a) paroxysmal AF b) permanent AF c) peri/post
cardioversion to sinus rhythm d) acute/post-op AF e) peri/post stroke f)
72
asymptomatic AF?
3. What is the efficacy of anticoagulation therapy versus antiplatelet
therapy for stroke prevention in: a) paroxysmal AF b) permanent AF c)
peri/post cardioversion to sinus rhythm d) acute/post-op AF e) peri/post
stroke f) asymptomatic AF?
4. What is the efficacy of antiplatelet therapy versus placebo for stroke
prevention in: a) paroxysmal AF b) permanent AF c) peri/post
asymptomatic AF?
5. What is the efficacy of vitamin K antagonist versus novel anticoagulant
for stroke prevention in: a) paroxysmal AF b) permanent AF c) peri/post
asymptomatic AF?
6. What is the role of point-of-care testing and self-monitoring of
anticoagulation.
7. How best to institute anticoagulant and antiplatelet therapy in patients
with AF undergoing percutaneous coronary intervention and non-ST
elevation myocardial infarction
8. In patients with AF what are the risks of long-term oral anticoagulation
therapy?
9. In patients with AF and vitamin K antagonist, what are the risk factors
associated with bleeding?
F. Long-term rate control

1. In patients with permanent AF, what is the efficacy of rate-limiting
calcium antagonists compared with digoxin in rate control?
2. In patients with permanent AF, what is the efficacy of beta-blockers
compared with digoxin in rate control?
3. In patients with permanent AF, what is the efficacy of beta-blockers
compared with rate-limiting calcium antagonists in rate control?
4. In patients with permanent AF, what is the efficacy of rate-limiting
calcium antagonists in combination with digoxin compared with rate-
limiting calcium antagonists monotherapy in rate control?
5. In patients with permanent AF, what is the efficacy of beta-blockers in
combination with digoxin compared with beta-blocker monotherapy in
rate control?
6. In patients with permanent AF, what is the efficacy of AV node ablation
with permanent pacemaker therapy in rate control?
G. Long-term rhythm control

1. In patients with paroxysmal AF, is flecainide/propafenone better than
beta-blockers in reducing the frequency of paroxysms?
2. In patients with paroxysmal AF, is amiodarone or sotalol better than
beta-blockers in reducing the frequency of paroxysms?
3. In patients with paroxysmal AF, is flecainide/propefanone better than
amiodarone or sotalol in reducing the frequency of paroxysms?
73
4. In patients with AF, is flecainide or propafenone better than beta-
blockers in maintaining sinus rhythm post cardioversion?
5. In patients with AF, is amiodarone or sotalol better than beta-blockers
in maintaining sinus rhythm post cardioversion?
6. In patients with AF, is flecainide/propafenone better than amiodarone or
sotalol in maintaining sinus rhythm post cardioversion?
7. Which antiarrhythmic agents should be chosen to maintain sinus rhythm
for patients with normal hearts?
8. Which antiarrhythmic agents should be chosen to maintain sinus rhythm
for patients with structural heart disease?
9. What is the efficacy of left atrial catheter ablation and surgical ablation
therapy for rhythm control in patients with a) paroxysmal AF b) persistent
AF?
10. What is the efficacy of cardiac pacing therapy for rhythm control in
patients with paroxysmal AF?
H. Referrals
1. Which patients with AF benefit from referral to specialist services for
assessment and management?
2. Which patients with AF benefit from referral to specialist services for
non-pharmacological treatment or electrophysiological studies?
APPENDIX C
C. WARFARIN IN PRACTICE
Barriers that may prevent people accessing medication and INR testing include:
• Financial barriers (including the ability to take time off work)
• Travel difficulties
• Lack of access to a telephone
• Fear or dislike of regular blood tests
• Difficulties with general practitioner monitoring.
Possible solutions include the following:

• Financial assistance from relevant agencies
• Provision of transport (e.g., shuttle service, taxi chits)
• Domiciliary testing, either at home or the work place
• Testing people in groups at a public health centre using a point-of-care monitor
C.1 INITIATION OF WARFARIN THERAPY
Loading doses are not recommended because they may increase the risk of
bleeding
Initiation of warfarin should be 5 mg daily in most patients (usually achieves INR
2 in 4-5 days)
A starting dose < 5 mg should be considered for patients >65 yrs, liver disease,
malnourished, severe heart failure, 74 or concomitant drugs affecting warfarin
metabolism.
• Difficulties with general practitioner monitoring.
Possible solutions include the following:

• Financial assistance from relevant agencies
• Provision of transport (e.g., shuttle service, taxi chits)
• Domiciliary testing, either at home or the work place
• Testing people in groups at a public health centre using a point-of-care monitor
C.1 INITIATION OF WARFARIN THERAPY
Loading doses are not recommended because they may increase the risk of
bleeding
Initiation of warfarin should be 5 mg daily in most patients (usually achieves INR
2 in 4-5 days)
A starting dose < 5 mg should be considered for patients >65 yrs, liver disease,
malnourished, severe heart failure, or concomitant drugs affecting warfarin
metabolism.
If overlapping LMWH or heparin with warfarin, overlap for at least 5 days.
Discontinue LMWH or heparin when INR is therapeutic on two consecutive
measurements 24 hr apart.
C.1.2 Frequency of INR Monitoring:
Check baseline INR prior to ordering warfarin

Check INR daily (AM lab) until therapeutic for two consecutive days then two-
three times weekly during initiation
C.1.2.1 Standard
Traditionally patients come into the clinic (or the hospital) to have venous blood
drawn for routine laboratory INR determination.
C.1.2.2 Point of Care
Finger tip capillary blood can be used with small, light weight and portable
instruments. The clinical trials result have compared favorably with traditional
INR determination.
Use in anticoagulation clinic.
Home use or Patient Self Test (PST)
x Need good quality control for point of care INR measurement.

o Patient selection is essential.
o Patients must have long-term indication for anticoagulation therapy.
o Patients must be willing and able to perform self-management.
o Patients must be willing to record results accurately and attend
clinics regularly for quality assurance.
o Patients must demonstrate competence in using the instrument and
interpreting the results.
o Patients must not have shown previous noncompliance in terms of
clinic attendance or medication management.
x Can increase INR testing frequency and decrease complications
associated with oral anticoagulation therapy.
C.1.3 Therapeutic INR Ranges:
AF alone: INR 2 – 3
Prosthetic Heart Valve: INR 2.5 – 3.5
C.1.4 Average Daily Dose
There are differences among various ethnic

75 groups
x Can increase INR testing frequency and decrease complications
associated with oral anticoagulation therapy.
C.1.3 Therapeutic INR Ranges:
AF alone: INR 2 – 3
Prosthetic Heart Valve: INR 2.5 – 3.5
C.1.4 Average Daily Dose
There are differences among various ethnic groups
About 4-5 mg/day or 28-35 mg/week for caucasian for target INR of 2.5 (2.0-3.0)
About 3-4 mg/day or 21-28 mg/week for Pacific-Asian (exclude caucasian in this
region). This dose will be less if target INR is recommended at <2.0.
C.1.5 Factors Effecting the Daily Dose
x Age ( For caucasian)

o <35 yr ----- 8.1 mg/day.
o 35-49 yr --- 6.4 mg/day.
o 50-59 yr --- 5.1 mg/day.
o 60-69 yr --- 4.2 mg/day.
o >70 yr ----- 3.6 mg/day.
x Genetic. Hereditary warfarin sensitive and resistance.
x Medicine noncompliance.
x Drugs interaction, including herbal medicine.
x Concurrent illness, fever, diarrhea, post op major surgery (i.e.. heart valve
replacement), malignancy, lupus anticoagulants.
x Impaired liver function, CHF with liver congestion.
x Food effect, vitamin K intake, alcohol.
x Hyperthyroidism, renal disease.
x During heparin and direct thrombin inhibitors treatment.
C.1.6 Warfarin Initiation
Day 1
(If there is an active or acute thromboembolic condition, warfarin should be

started along with heparin, unless there is a contraindication or patient cannot
take medicine orally. Following warfarin initiation, heparin should be continued
until INR reaches therapeutic level for 2 days).
5 mg (2.5-7.5). This dose is a good choice since it is known that average daily
dose is close to 5 mg. Using higher dose than necessary may lead to bleeding
complication due to rapidly and severely reduce factor VII. It may deplete protein
C too quick, and theoretically can cause hypercoagulable state. The 5 mg size
tablet is recommended for both inpatient and outpatient use, making inpatient to
outpatient transition more convenient. It is the most commonly used size tablet
by the majority of anticoagulation clinics today.
The higher dose warfarin initiation has also been tested successfully by using
normogram. It may be considered in patient who may need shorter period of time
to reach therapeutic INR. It should be done as inpatient. INR have to be done
frequently enough to prevent over anticoagulation and bleeding complication
Use lower dose (2.5 mg).

x >80 yr.
x Concurrent illness.
x On interaction drug. 76
x S/P major surgery, i.e. heart valve surgery.
outpatient transition more convenient. It is the most commonly used size tablet
by the majority of anticoagulation clinics today.
The higher dose warfarin initiation has also been tested successfully by using
normogram. It may be considered in patient who may need shorter period of time
to reach therapeutic INR. It should be done as inpatient. INR have to be done
frequently enough to prevent over anticoagulation and bleeding complication
Use lower dose (2.5 mg).

x >80 yr.
x Concurrent illness.
x On interaction drug.
x S/P major surgery, i.e. heart valve surgery.
x Chronic malnourished.
x Impaired liver function, liver congestion.�
Use higher dose (7.5-10.0 mg).
x Young healthy subject.
x In the first two days.
Day 2
A. If INR <1.5, continue the same dose.

B. If INR >1.5, give lower dose (2.5 mg or none)
Day 3
For #A. of Day 2
x If INR <1.5, suggests a higher than average maintenance dose of 5
mg/day or 35 mg/week will be needed. Give higher dose than 5 mg. i.e.7.5
mg for now.
x If INR 1.5-2.0, suggests an average maintenance dose close to 5 mg/day
or close to 35 mg/week will be needed, and continue 5 mg for now.
x If INR >2.0, suggests a lower than average maintenance dose of 5 mg/day
or 35 mg/week will be needed. Give less than 5 mg, i.e.2.5 mg or none for
now.
For #B. of Day 2
x If INR 1.5-2.0, suggests daily dose will be close to or less than 5 mg/day
or close to 35 mg/week or less. May give 5 mg or less for now.
x If INR >2.0, suggests daily dose will be lower than 5 mg/day or less than
35 mg/week. May give 2.5 mg or none for now.
Day 4
If there is no need for heparin therapy, the patient may have been discharged by
now, and warfarin initiation is continued as an outpatient.
x INR 2 times a week until INR is in target range twice in a row, then INR 1
time weekly until INR is in target range twice in a row, then INR 1 time in 2
week until INR is in target range twice in a row, then enter the patient in to
maintenance schedule (usually INR every 4 weeks).
x Patients during an acute illness, or post operative of major surgeries may
be more sensitive to warfarin than when they become more stable.
Out patient (See also "Day 4" above)
x Obtain baseline INR

x Start with 5 mg daily. See more detail for dose variation in "Inpatient
guideline"
x Check INR 2 times a week, or more often if necessary, during the first
week or so. Adjust warfarin dose and timing for INR check as outline in
"Inpatient" guidelines.
77
C.1.7 Ethnic Difference for Chinese-Asian or Pacific-Asian (exclude caucasian in
x Obtain baseline INR
x Start with 5 mg daily. See more detail for dose variation in "Inpatient
guideline"
x Check INR 2 times a week, or more often if necessary, during the first
week or so. Adjust warfarin dose and timing for INR check as outline in
"Inpatient" guidelines.
C.1.7 Ethnic Difference for Chinese-Asian or Pacific-Asian (exclude caucasian in

this region)
x Average daily dose of Warfarin for Pacific-Asian (exclude caucasian in this

region) or Chinese-Asian is about 3 mg. Weekly dose is about 21-28 mg,
or lower if "target INR" for various diagnoses are about 0.4-0.5 lower than
those of Caucasian-American-European level.
x "Target INR" for or Pacific-Asian (exclude caucasian in this region) or
Chinese-Asian should be lower than those of Caucasian-American-
European. The suggest level for nonvalvular atrial fibrillation is 1.6-2.6, to
achieve less combine thromboembolic and major bleeding events. (Need
more database for confirmation)
x Difference in polymorphism of CYP 2C9 and VKORC1which will influence
Warfarin dosage
Warfarin Initiation Table for average daily dose of 5 mg and 3 mg further
INR DOSE
DAY
INPATIENT OUTPATIENT
(Usually with daily INR)
Normal 5.0 mg 5.0 mg
1 (2.5 or 7.5-10.0 mg in patients listed in the (2.5 or 7.5-10.0 mg in patients listed in the text)
text)
< 1.5 5.0 mg 5.0 mg
> 1.5 0.0 - 2.5 mg 0.0 - 2.5 mg
2
[If INR is not measured
5.0 mg]
< 1.5 5.0 - 10 mg 5.0 - 10 mg
1.5 - 1.9 2.5 - 5.0 mg 2.5 - 5.0 mg
2.0 - 3.0 0.0 - 2.5 mg 0.0 - 2.5 mg
3 > 3.0 0.0 mg 0.0 mg
INR should be measured today. If INR is not measured,
may use the same dose as day 2, and should not > 5 mg
< 1.5 10.0 mg 10.0 mg

1.5 - 1.9 5.0 - 7.5 mg 5.0 - 7.5 mg
2.0 - 3.0 0.0 - 5.0 mg 0.0 - 5.0 mg
4 > 3.0 0.0 mg 0.0 mg
INR measurement should be done, if INR on day 3 is < 1.5
or > 3.0
< 1.5 10.0 - mg 10.0 - mg
1.5 - 1.9 7.5 - 10.0 mg 7.5 - 10.0 mg
2.0 - 3.0 0.0 - 5.0 mg 0.0 - 5.0 mg
5 > 3.0 0.0 mg 0.0 mg
or > 3.0
< 1.5 7.5 - 12.5 mg 7.5 - 12.5 mg
1.5 - 1.9 5.0 - 10.0 mg 5.0 - 10.0 mg
2.0 - 3.0 0.0 - 7.5 mg 0.0 - 7.5 mg
> 3.0 0.0 mg 0.0 mg
or > 3.0
Note: Frequent INR measurement during warfarin initiation helps prevent bleeding from over anticoagulation and helps reaching target INR
sooner.
78
DOSE
DAY INR
INPATIENT
OUTPATIENT
(Usually with daily INR)
Normal 3.0 mg 3.0 mg

1 (1.5 or 3.0-6.0 mg in patients listed in the text) (1.5 or 3.0-6.0 mg in patients listed in the text)
3.0 mg 3.0 mg
< 1.3 0.0 - 1.5 mg 0.0 - 1.5 mg
> 1.3
2
[If INR is not measured
3.0 mg (1.5-4.5)]
< 1.3 3.0 - 6 mg 3.0 - 6 mg

1.3 - 1.6 1.5 - 3.0 mg 1.5 - 3.0 mg
1.6 - 2.6 0.0 - 1.5 mg 0.0 - 1.5 mg
> 2.6 0.0 mg 0.0 mg
3
INR should be measured today. If INR is not measured,
may use the same dose as day 2, and should not > 3.0 mg
< 1.3 4.5 - 6.0 mg 4.5 - 6.0 mg

1.3 - 1.6 3.0 - 4.5 mg 3.0 - 4.5 mg
1.6 - 2.6 1.5 - 3.0 mg 0.0 - 3.0 mg
4 > 2.6 0.0 mg 0.0 mg
or > 2.6
< 1.3 6.0 - 7.5 mg 6.0 - 7.5 mg
1.3 - 1.6 3.0 - 4.5 mg 3.0 - 4.5 mg
1.6 - 2.6 1.5 - 3.0 mg 1.5 - 3.0 mg
5 > 2.6 0.0 mg 0.0 mg

or > 2.6
< 1.3 6.0 - 7.5 mg 6.0 - 7.5 mg

1.3 - 1.6 4.5 - 6.0 mg 4.5 - 6.0 mg
1.6 - 2.6 1.5 - 3.0 mg 1.5 - 3.0 mg
6 > 2.6 0.0 mg 0.0 mg
or > 2.6
Note: Frequent INR measurement during warfarin initiation helps prevent bleeding from over anticoagulation and helps reaching target INR sooner.
C.1.8
C.1.8Dose
DoseAdjustments
Adjustmentsfor
forWarfarin
WarfarinMaintenance
Maintenance Therapy
Therapy (Target INR 2.0-3.0)
2.0-3.0)
INR
INR Dose Adjustments
Dose Adjustments
1.5
1.5 Increaseweekly
Increase weekly dose
dose by
by 20%
1.5-1.9
1.5-1.9 Increaseweekly
Increase weekly dose
dose by 10%
2.0-3.0
2.0-3.0 No change
No change
3.1-3.9
3.1-3.9 Nochange;
No change;ififpersistent
persistentdecrease
decrease weekly
weekly dose
dose by
by 10-20%
10-20%
4.0-5.0
4.0-5.0 Omit11dose;
Omit dose;decrease
decrease weekly
weekly dose
dose by
by 10-20%
10-20%
!5.0
!5.0 Seerecommendations
See recommendations for for managing
managing elevated
elevated INR
INR
Whenresume
When resumedecrease
decrease weekly
weekly dose
dose 20-50%
20-50%
79
C.1.8.1
C.1.8.1 Recommendationsfor
Recommendations forManaging
ManagingElevated
ElevatedINRs INRs or or Bleeding
Bleeding in Patients
C.1.8.1
Receiving
Receiving Recommendations
Warfarin:
Warfarin: for Managing Elevated INRs or Bleeding in Patients
Receiving Warfarin:
Condition
Condition Recommendation
Recommendation
INRINR Condition
above
above Lowerthe
Lower thedose
doseororomit Recommendation
omit aadose
doseand and resume
resume with with lower
lower dose
dose
INR aboverange
therapeutic
therapeutic range when Lower
whenINR thetherapeutic;
INR dose or omitififaonly
therapeutic; dose
only and resume
minimally
minimally above
above with lower dose
therapeutic
therapeutic
buttherapeutic
but nono range range,
5;
5; when
range,no INR therapeutic;
nodose
dose reduction
reduction if only
mayminimally
may be required.
be required.above therapeutic
but 5; no
significant
significant bleeding range, no dose reduction may be required.
bleeding
significant
INR 5 but
t but bleeding Omitnext nextone
oneorortwo twodoses,
doses,monitor
monitor INR INR more
more frequently,
frequently,
INR t5 9;9;nono Omit
INR t 5 but
significant 9; no and
bleeding Omit next one
andresume
resume with
with orlower
two doses,
lower dosewhen
dose monitor
when INR
INR INR more frequently,
therapeutic.
therapeutic. If
If risk
risk of
of
significant bleeding
and
significant bleeding bleeding, resume
bleeding, with
omit
omit thelower
the dose and
nextdose
next when
and give INRvitamin
give therapeutic.
vitamin K 1-2.5
K 1-2.5If risk
mg of
mg
bleeding,
PO.
PO. omit the next dose and give vitamin K 1-2.5 mg
INR t 9; PO.
Holdwarfarin
warfarinand andgivegiveVitamin
VitaminKK 2.5-5 2.5-5 mg mg orally;
orally; expect
INR t 9; nono Hold expect
INR t 9; nobleeding Hold
significant warfarin
substantial INR and give Vitamin
reduction K 2.5-5Monitor
in 24-48hr. mg orally;INRexpect
more
significant bleeding substantial INR reduction in 24-48hr. Monitor INR more
significant bleeding substantial
frequently and INRrepeat
reduction
vitaminin 24-48hr. Monitor Resume
K if necessary. INR more
frequently
frequently
and repeat vitamin K if necessary. Resume
warfarin atand repeat vitamin
an adjusted dose when K if necessary. Resume
INR therapeutic.
warfarin
warfarinatatan anadjusted
adjusteddosedosewhen when INR INR therapeutic.
therapeutic.
Serious bleeding at Hold warfarin and give vitamin K 10 mg slow IV infusion,
Serious
Serious bleeding ofatat Hold
bleeding
any elevation Hold warfarin
warfarinand
supplemented and
withgive
givevitamin
FFP,vitamin KK 10
prothrombin 10 mgmg slow
slow IV
complex infusion,
IVconcentrate
infusion,
anyany
INRelevation
elevationofof supplemented
supplemented
or rVIIa, depending with
withFFP,
FFP, prothrombin
prothrombin
on urgency complex
complex
of situation. concentrate
concentrate
Vitamin K can
INRINR ororrVIIa,
rVIIa,depending
depending
be repeated q12hr on
on urgency
urgency of
of situation.
situation. Vitamin
Vitamin K can
K can
Life threatening bebe repeated
repeated q12hr
q12hr
Hold warfarin and give FFP, prothrombin complex
Life threatening
Life threatening
bleeding Hold
Hold warfarin
warfarinand
concentrate, orand give
give
rVIIa FFP,
FFP,prothrombin
supplementedprothrombin complex
complex
with vitamin K 10 mg
bleeding
bleeding concentrate,
concentrate,
slow IV infusion.ororrVIIa
rVIIa supplemented
supplemented
Repeat, if necessary, with vitamin
vitamin K
withdepending 10
K 10 mg
on mg
INR.
slow
slowIVIVinfusion.
infusion. Repeat,
Repeat,ififnecessary,
necessary, depending
depending on on INR.
INR.
C.1.9 Interruption of Warfarin Therapy for Surgery

C.1.9 Interruption
C.1.9 InterruptionofofWarfarin
WarfarinTherapy
Therapyfor
forSurgery
Surgery
Condition Recommendations
Condition
LowCondition
risk of Recommendations
Stop warfarin 5 daysRecommendations
before surgery allowing INR to return
Low
Lowrisk ofof
risk
thromboembolism Stop
Stop warfarin
to near warfarin 55days
normal. days before
before
Bridge surgery
with allowing
surgery
therapy doseINR
allowing
low LMWH return
to return
or no
thromboembolism
thromboembolism totonear
nearnormal.
bridging. normal. Bridge
Bridgetherapy
therapy with
with low
low dose
dose LMWH or no no
Moderate risk of bridging.
bridging.
Stop warfarin 5 days before surgery allowing INR to fall,
Moderate
Moderate riskofof
risk
thromboembolism Stop
Stop warfarin
startwarfarin
bridge 55days
dayswith
therapy before
before surgery allowing
surgery
therapeutic allowing
dose LMWH to fall,
INR 2-3 days
thromboembolism
thromboembolism start
start bridge
priorbridge therapy
therapy
to surgery withtherapeutic
with
(or when therapeutic dose LMWH 2-3
dose
INR is sub-therapeutic). 2-3 days
days
prior totosurgery
Administer
prior surgery (orwhen
last(or
dose when
of LMWHINRisis24
INR sub-therapeutic).
hrs before surgery.
sub-therapeutic).
High risk of Administer
Administer
Stop warfarin last dose
last 5dose of LMWH
daysofbefore
LMWH 24 hrs before
24 hrsallowing
surgery surgery.
before surgery.
INR to fall,
High risk
ofof
thromboembolism
High risk Stop warfarin
startwarfarin
Stop bridge 55days
dayswith
therapy before
before surgery allowing
therapeutic
surgery allowing
dose LMWH INR 2-3
INR to
to fall,
days
fall,
thromboembolism
thromboembolism start bridge
priorbridge
start therapy
to surgery
therapy with
(or when therapeutic dose LMWH 2-3
dose LMWH
INR is sub-therapeutic).
with therapeutic 2-3 days
days
prior
prior to
Administer surgery (or
last(or
to surgery dose when
of LMWH
when INR is sub-therapeutic).
INR is 24hrs before surgery.
sub-therapeutic).
Low risk of Administer
Lower warfarin
Administer last dose of
last dose ofand LMWH
LMWH operate24hrs
at an
24hrs before surgery.
INR of
before 1.3-1.5; the
surgery.
Low risk
bleeding
Low risk ofof Lower warfarin
dose warfarin
Lower may doseand
be lowered
dose and operate
4-5operate at an
days before
at ansurgery;
INR of
INR of 1.3-1.5;
1.3-1.5;
warfarinthe
thecan
bleeding
bleeding dose
be may
restartedbe lowered
post-op, 4-5 days
supplement before
with
dose may be lowered 4-5 days before surgery; warfarinsurgery;
LMWH if warfarin
necessary. can
can
beberestarted
restartedpost-op,
post-op,supplement
supplement with with LMWH
LMWH ifif necessary.
necessary.
Urgent surgical or For immediate reversal give FFP, prothrombin complex
Urgent
Urgent surgicaloror
other surgical
invasive For immediate
concentrate
For immediate reversal
inreversal give
additiongive FFP, prothrombin
to vitamin
FFP, prothrombin
K 2.5-5 mg po complex
or by slow
complex
other invasive
procedure (within concentrate
IV infusion. ininaddition
addition to vitamin K 2.5-5 mg po or by slow
other invasive concentrate to vitamin K 2.5-5 mg po or by slow
procedure
12 (within
hours)(within IV infusion.
procedure IV infusion.
12 hours)
12Urgent
hours)surgical or If surgery is urgent but can be delayed for 18-24 hrs give
Urgent surgical or If surgery is urgent but can be delayed for 18-24 hrs give
Urgent surgical or If surgery is urgent but can be delayed for 18-24 hrs give
80
other invasive vitamin K 2.5- 5 mg po or by slow IV infusion. If INR is still
procedure (within high, additional vitamin K 1-2 mg po can be given.
18-24 hours)
Low risk: VTE: Single VTE occurred >12 months ago and no other risk factors,
AF: (CHADS2 score 0-2) without a history of stroke or other risk factors, Mech
heart valve: bileaflet aortic valve without AF and no other risk factors for stroke.
Moderate risk: VTE: VTE within 3-12 months, non-severe thrombophilic

conditions, recurrent VTE, active cancer, AF: (CHADS2 score 3 or 4), Mech heart
valve: bileaflet aortic valve and one of the following: AF, prior stroke or TIA, HTN,
DM, CHF, age >75 yr.
High risk: VTE: recent (within 3mo) VTE, severe thrombophilia, AF:(CHADS2
score 5 or 6), recent (within 3 months) stroke or TIA, rheumatic valvular heart
disease,
Mech heart valve: any mitral valve prosthesis, older aortic valve prosthesis
(caged-ball or tilting disc), recent (within 6 months) stroke or TIA
x Resume warfarin therapy 12-24 hrs after surgery and when there is
adequate hemostasis.
x Resume bridge therapy:
o Minor surgery or other invasive procedure and receiving therapeutic
dose LMWH: Resume 24 hrs after the procedure when there is
adequate hemostasis
o Major surgery or high bleeding risk surgery/procedure where post-
op therapeutic dose LMWH is planned: delay initiation of
therapeutic dose LMWH for 48-72 hours after surgery when
hemostasis is secured or administering low dose LMWH after
surgery when hemostasis is secured or completely avoiding LMWH
after surgery.
81
APPENDIX D
Vaughn Williams Classification of Antiarrhythmic Drugs
Type IA
Disopyramide
Procainamide
Quinidine
Type IB
Lignocaine
Mexilitine
Type IC
Flecainide
Propafenone
Type II
Beta blockers (e.g. propranolol)
Type III
Amiodarone
Dronedarone
Bretylium
Dofetilide
Ibutilide
Sotalol
Type IV
Nondihydropyridine calcium channel antagonist (verapamil and diltiazem)
Table includes compounds introduced after publication of the original classification.
82
Glossary
ACEI Angiotensin Converting Enzyme Inhibitor

ACS Acute Coronary Syndrome
AF Atrial fibrillation
AFl Atrial Flutter
AFFIRM Atrial Fibrillation Follow-up Investigation of Rhythm
Management
AP Accessory Pathway
AV Atrioventricular
ARB Angiotensin Receptor Blocker
BAFTA Birmingham Atrial Fibrillation Treatment of the Aged
bpm Beats per minute
CCB Calcium Channel Blocker
CAD Coronary Artery Disease
CCS-SAF Canadian Cardiovascular Society Severity in Atrial Fibrillation
CHA2DS2VASc Congestive Heart Failure, Hypertension, Age, Diabetes
Mellitus and Stroke, Vascular Disease
CHADS2 Congestive Heart Failure, Hypertension, Age, Diabetes
Mellitus and Stroke
CHF Congestive Heart Failure
COPD Chronic Obstructive Pulmonary Disease
CPR Cardiopulmonary Resuscitation
CRT Cardiac Resynchronisation Therapy
CT Computed tomography
CV Cardioversion
CYP Cytochrome P
DCCV Direct Current Cardioversion
DM Diabetes Mellitus
EAPCI European Association of Percutaneous Cardiovascular
Interventions
ECG Electrocardiogram
EHRA European Heart Rhythm Association
GPI Glycoprotein IIb/IIIa Inhibitor
HAS-BLED Hypertension, Abnormal renal and liver function, Stroke,
Bleeding, Labile INR, Elderly, Drugs
HCM Hypertrophic Cardiomyopathy
HF Heart Failure
HOT CAFÉ HOw to Treat Chronic Atrial Fibrillation
HTN Hypertension
ICD Implantable Cardioverter Defibrillator
83
INR International Normalised Ratio
IV Intravenous
J-RHYTHM Japanese Rhythm Management Trial for Atrial Fibrillation
LA Left atrium
LAA Left atrial appendage
LMWH Low molecular weight heparin
LoE Level of Evidence
LV Left ventricle
LVEF Left Ventricular Ejection Fraction
LVH Left Ventricular Hypertrophy
MI Myocardial Infarction
N/A Not available
ND Not Determined
NYHA New York Heart Association
OAC Oral Anticoagulant
PAD Peripheral Artery Disease
PAF Paroxysmal atrial fibrillation
PCI Percutaneous Intervention
PIAF Pharmacological Intervention in Atrial Fibrillation
PUFA Polyunsaturated fatty acids
PVI Pulmonary Vein Isolation
RACE RAte Control versus Electrical CardioversionFor Persistent
Atrial Fibrillation
RE-LY Randomised Evaluation of Long-Term Anticoagulation
Therapy
SCD Sudden Cardiac Death
SR Sinus Rhythm
STAF Strategies of Treatment of Atrial Fibrillation
TE Thromboembolism
TE risk Thrombo-embolic risk
TIA Transient ischemic attack
TOE Transesophageal echocardiogram
TTE Transthoracic echocardiogram
UFH Unfractionated Heparin
VHD Valvular Heart Disease
VKA Vitamin K Antagonist
VTE Venous Thromboembolism Prophylaxis
WPW Wolff-Parkinson-White Syndrome
84
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This clinical practice guideline comprises [a] figure[s] from the ESC
Guidelines for the Management of Atrial Fibrillation (“ESC Guidelines”)
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THE PUBLICATION of the Clinical Practice Guidelines for Atrial Fibrillation

In a broader sense, these guidelines emphasized that AF is a worldwide public

This latest version has undergone extensive revision in response to comments

In a voluntary and multidisciplinary undertaking of this magnitude, many individuals

Professor Dr. Sim Kui Hian FNHAM

GUIDELINE DEVELOPMENT PROCESS

Evidence was obtained by systematic review of current medical literature on Atrial

Reference was also made to other guidelines on Atrial Fibrillation, Guidelines

Clinical Issues Addressed

1. How do you assess a patient suspected of having atrial fibrillation?

This CPG is directed at all healthcare providers treating patients with AF –

Implementation of the Guidelines

To ensure successful implementation of this CPG we suggest:

1. Constant checks and feedback on whether the guideline is relevant.

2. Identify implementation leaders

Identification of multiple leaders to share the implementation work and ensure

3. Identify an implementation group

Support from medical associations such as the Private Medical Practitioners

4. Carrying out a baseline assessment

5. Developing an action plan

The baseline assessment will have identified which recommendations are

6. Key areas for implementation

Datuk Dr Hj Azhari b Rosman,

Dato’ Dr Chang Kian Meng

Dr Ernest Ng Wee Oon

Associate Professor Dr Imran b Zainal Abidin

Dr Lai Voon Ming

Dr Ngau Yen Yew

Dato’ Dr Omar b Ismail,

Prof. Madya Dr Oteh b Maskon

Datuk Dr Raihanah bt Abdul Khalid

Dr Ridzuan b Dato Mohd Isa

1) Dato’ Dr Ravindran Jegasothy

2) Datuk Dr Razali b Omar

3) Professor Dr Sim Kui Hian

4) Dato’ Dr. Sree Raman

1 An electrocardiogram (ECG) should be performed in all patients, whether

2 The stroke risk stratification algorithms, CHADS2 and CHA2DS2VASc,

3 Antithrombotic therapy should be based upon the absolute risks of stroke/

4 When choosing either an initial rate-control or rhythm-control strategy, the

5 When choosing an antiarrhythmic agent for rhythm control strategy, safety

II-bII-b Usefulness/efficacy is less

Adapted from the American Heart Association/American College of Cardiology (AHA/

Atrial fibrillation (AF) is an atrial tachyarrhythmia characterized by uncoordinated

Atrial Flutter (AFl) in the typical form is characterized by a saw-tooth pattern of

1.2 TYPES OF ATRIAL FIBRILLATION

‘Silent AF’ being asymptomatic is detected by an opportunistic ECG or may

1.4 EPIDEMIOLOGY AND PROGNOSIS

AF is the commonest sustained cardiac arrhythmia. Information on AF in

Data from predominantly western populations suggest the estimated prevalence

AF is associated with a prothrombotic state, intra-atrial stasis, structural heart

Hospitalizations are frequent in

Stroke in AF is often severe and results in long-term disability or death.

Understanding the pathophysiology of atrial brillation (AF) requires integration

2.1 CLINICAL ASPECTS

2.1.1 CAUSES AND ASSOCIATED CONDITIONS

AF is often associated with co-existing medical conditions. The underlying

Table 3: Common cardiac and non-cardiac risk factors of AF.

AF is often associated with co-existing medical conditions. The underlying

Some of the conditions predisposing to AF may be reversible such as acute

Approximately 30 – 40% of cases of paroxysmal AF and 20 – 25% of persistent

Rhythm control is recommended in patients with symptomatic (EHRA class 2)