Review

doi: 10.1111/joim.12468

A tailored treatment strategy: a modern approach for stroke

prevention in patients with atrial fibrillation
G. Y. H. Lip1,2, T. Potpara3, G. Boriani4 & C. Blomstr€om-Lundqvist5
From the 1University of Birmingham Institute of Cardiovascular Sciences, Birmingham, UK; 2Aalborg Thrombosis Research Unit, Department
of Clinical Medicine, Aalborg University, Aalborg, Denmark; 3Cardiology Clinic, Clinical Centre of Serbia, School of Medicine, University of
Belgrade, Belgrade, Serbia; 4Institute of Cardiology, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna,
S.Orsola-Malpighi University Hospital, Bologna, Italy; and 5Department of Cardiology, Institution of Medical Science, Uppsala University,
Uppsala, Sweden

Content List – Read more articles from the symposium: Atrial fibrillation - from atrial extrasystoles to atrial
cardiomyopathy. What have we learned from basic science and interventional procedures

Abstract. Lip GYH, Potpara T, Boriani G, Blomstr€ om-
Lundqvist C (University of Birmingham Institute of
Cardiovascular Sciences, Birmingham, UK; Aalborg
University, Aalborg, Denmark; University of Belgrade,
Belgrade, Serbia; University of Bologna, S.Orsola-
Malpighi University Hospital, Bologna, Italy; Uppsala
University, Uppsala, Sweden). A tailored treatment
strategy: a modern approach for stroke prevention in
patients with atrial fibrillation. (Review Symposium).
J Intern Med 2016; 279: 467–476.
The main priority in atrial fibrillation (AF) manage-
ment is stroke prevention, following which deci-
sions about rate or rhythm control are focused on
the patient, being primarily for management of
symptoms. Given that AF is commonly associated
with various comorbidities, risk factors such as
hypertension, heart failure, diabetes mellitus and
sleep apnoea should be actively looked for and
managed in a holistic approach to AF management.
The objective of this review is to provide an
overview of modern AF stroke prevention with a
focus on tailored treatment strategies. Biomarkers
and genetic factors have been proposed to help
identify ‘high-risk’ patients to be targeted for oral
anticoagulation, but ultimately their use must be
balanced against that of more simple and practical
considerations for everyday use. Current guideli-
nes have directed focus on initial identification of
‘truly low-risk’ patients with AF, that is those
patients with a CHA2DS2-VASc [congestive heart
failure, hypertension, age ≥75 years (two points),
diabetes mellitus, stroke (two points), vascular
disease, age 65–74 years, sex category] score of 0
(male) or 1 (female), who do not need any
antithrombotic therapy. Subsequently, patients
with ≥1 stroke risk factors can be offered effective
stroke prevention, that is oral anticoagulation. The
SAMe-TT2R2 [sex female, age <60 years, medical
history (>2 comorbidities), treatment (interacting
drugs), tobacco use (two points), race non-Cauca-
sian (two points)] score can help physicians make
informed decisions on those patients likely to do
well on warfarin (SAMe-TT2R2 score 0–2) or those
who are likely to have a poor time in therapeutic
range (SAMe-TT2R2 score >2). A clinically focused
tailored approach to assessment and stroke pre-
vention in AF with the use of the CHA2DS2VASc,
HAS-BLED [hypertension, abnormal renal/liver
function (one or two points), stroke, bleeding
history or predisposition, labile international nor-
malized ratio, elderly (>65 years) drugs/alcohol
concomitantly (one or two points)] and SAMeTT2R2
scores to evaluate stroke risk, bleeding risk and
likelihood of successful warfarin therapy, respec-
tively, is discussed.
Keywords: atrial fibrillation, bleeding, stroke.

The main priority in AF management is stroke pre-

Introduction
Atrial fibrillation (AF) is the commonest cardiac
arrhythmia, with an increasing prevalence with age
and common cardiovascular disorders. Thus, AF is
an important healthcare issue and early detection
provides an opportunity to prevent fatal and dis-
abling strokes.
vention, after which decisions about rate or rhythm
control are largely patient-centred and symptom
directed. Given that AF is commonly associated with
various comorbidities, associated risk factors such as
hypertension, heart failure, diabetes mellitus and
sleep apnoea should be proactively investigated and
managed in a holistic approach to AF management.

ª 2016 The Association for the Publication of the Journal of Internal Medicine 467
 G. Y. H. Lip et al.
Here, our objective was to provide an overview of
modern AF stroke prevention with a focus on
practical, tailored treatment strategies.
Rationale for opportunistic screening for AF
AF is very common and is present in 3–6% of acute
medical admissions. Given the missed opportuni-
ties for stroke prevention, screening for AF has
been proposed in recent guidelines [1].
Approximately a third of AF patients are asymp-
tomatic, and such patients may have a poorer
prognosis compared with symptomatic patients [2].
Martinez et al. [3] reported the findings of a cohort
study of 5555 patients with incidentally detected
ambulatory AF where asymptomatic AF was sig-
nificantly associated with a high risk of stroke and
death. Importantly, there was reduction in the risk
of both stroke and death with oral anticoagulants
(OACs) but not with antiplatelet treatment. Even in
the historical randomized trials, OACs reduced the
risk of stroke/systemic embolism by 64% and all-
cause mortality by 26%, compared with controls/
placebo [4].
Lowres et al. [5] conducted a systematic review of
screening to identify unknown AF and concluded
that the prevalence of AF across all included
studies was 2.3% [95% confidence interval (CI)
2.2–2.4%], increasing to 4.4% (95% CI 4.1–4.6%) in
those aged ≥65 years. This is perhaps unsurprising
given the increasing prevalence of AF with increas-
ing age. Of note, the authors found that the overall
incidence of previously unknown AF was 1.0%
(95% CI 0.89–1.04%), increasing to 1.4% (95% CI
1.2–1.6%) in those aged ≥65 years [5]. Of those
with previously unknown AF, 67% were at high risk
of stroke, perhaps justifying how community AF
screening strategies in older age groups could
potentially provide stroke prevention opportunities
and reduce the overall health burden associated
with AF-related stroke.
In the community setting, opportunistic or system-
atic screening for AF was tested in the Screening for
AF in the Elderly (SAFE) trial [6]; the results
showed that opportunistic screening was the more
cost-effective strategy compared with systematic
screening. Given that common cardiovascular dis-
orders all contribute to AF and its complications,
initial focus on screening for AF in such patients
with associated comorbid risk factors allows better
opportunity for detecting AF.
468 ª 2016 The Association for the Publication of the Journal of Internal Medicine
Journal of Internal Medicine, 2016, 279; 467–476
Review Symposium: Tailored stroke prevention
In another community study, conducted by Eng-
dahl et al. [7], all inhabitants in the municipality of
Halmstad, Sweden aged 75–76 years were invited
to take part in a stepwise screening programme for
AF. As a first step, participants recorded a 12-lead
electrocardiogram (ECG) and reported their rele-
vant medical history. In step 2, those in sinus
rhythm according to the 12-lead ECG, no history of
AF and ≥2 risk factors according to CHADS2
[congestive heart failure, hypertension, age
≥75 years, diabetes mellitus, stroke (two points)]
score were invited to participate in a 2-week
recording period using a hand-held ECG device.
Previously undiagnosed silent AF was found in 1%
of 848 individuals who recorded a 12-lead ECG,
and 43% of the 81 patients with known AF were not
receiving OAC treatment. Amongst the 403 persons
with ≥2 risk factors for stroke, 7.4% were diag-
nosed with paroxysmal AF. Thus, a stepwise risk
factor-stratified AF screening programme in a
population of 75-year-old individuals yields a large
proportion of high-risk AF patients eligible for OAC
treatment. Broadly similar findings were reported
from the STOPSTROKE (Systematic ECG Screening
for Atrial Fibrillation Among 75 Year Old Subjects
in the Region of Stockholm and Halland, Sweden)
study [8], where of 7173 elderly participants (age
75–76 years) in a screening programme, 3.0% were
found to have previously unknown AF. A prior
diagnosis of AF was found in 9.3%, and the total AF
prevalence in the screened population was 12.3%.
Overall, 5.1% of the screened elderly population
had untreated AF [8].
Other results were reported from the SEARCH-AF
study, in which community screening for unknown
AF was examined in pharmacies using an iPhone
ECG (iECG) and cost-effectiveness was determined
[9]. In SEARCH-AF, pharmacists performed pulse
palpation and iECG recordings in 1000 pharmacy
customers aged ≥65 years (mean 76  7 years;
44% male), with cardiologist iECG over-reading.
Newly identified AF was reported in 1.5% of the
cohort and all patients had a CHA2DS2-VASc score
≥2. Thus, AF prevalence was 6.7% and the auto-
mated iECG algorithm showed 98.5% sensitivity
for AF detection and 91.4% specificity. Such a
community-based AF screening programme was
also found to be cost-effective.
What about noncommunity settings? Even in
patients presenting with an ischaemic stroke, more
intense monitoring would allow a higher rate of
detection of AF; that is, the harder one looks the
 G. Y. H. Lip et al.
more likely it is that AF will be found. In a
systematic review, Sposato et al. [10] examined
the proportion of patients diagnosed with post-
stroke AF in four different phases: (i) phase 1
(emergency department) consisted of admission
ECG; (ii) phase 2 (in hospital) comprised serial
ECG, continuous inpatient ECG monitoring, con-
tinuous inpatient cardiac telemetry and in-hospital
Holter monitoring; (iii) phase 3 (first ambulatory
period) consisted of ambulatory Holter; and phase
4 (second ambulatory period) consisted of mobile
cardiac outpatient telemetry, external loop record-
ing and implantable loop recording. The authors
concluded that poststroke AF occurred in 7.7% of
patients (95% CI 5.0–10.8) in phase 1, 5.1% (3.8–
6.5) in phase 2, 10.7% (5.6–17.2) in phase 3 and
16.9% (13.0–21.2) in phase 4. The overall AF
detection yield after all phases of sequential car-
diac monitoring was 23.7% (95% CI 17.2–31.0)
[10]. Thus, by sequentially combining cardiac
monitoring methods, AF might be newly detected
in nearly a quarter of patients presenting with
stroke or transient ischaemic attack. Accordingly,
more stroke recurrences could be prevented in this
high-risk population.
Even in patients considered to have cryptogenic
stroke (more recently referred to as ‘embolic stroke
of uncertain source’ [11]), mobile cardiac outpa-
tient telemetry detects AF in a substantial propor-
tion [12]. In a study by Favilla et al. [12], for
example, age >60 years and radiographic evidence
of prior cortical or cerebellar infarction were good
indicators of occult AF. With improving technology
for detecting AF, the diagnosis of cryptogenic
stroke may become less easy to justify.
Are efficacy and safety of anticoagulation improved if tailored to the
patient’s profile? The role of genes and biomarkers
Whilst AF increases the risk of stroke five-fold
overall, this risk is not homogeneous and is
dependent upon the presence of various stroke
risk factors. In earlier guidelines, the initial focus
was to identify patients at high risk of stroke, to be
targeted for OAC therapy, given that until recently
the only OACs available were the vitamin K antag-
onists [(VKAs) e.g. warfarin].
Risk factors for stroke in AF have been used to
formulate stroke risk stratification schemes. For
example, the CHADS2 score was proposed for
stroke risk assessment, categorizing patients as
low risk (score = 0), moderate risk (score = 1) and
Review Symposium: Tailored stroke prevention
high risk (score ≥2) [13]. A categorical approach to
stroke risk stratification and treatment decisions
artificially divides patients into low-, moderate-
and high-risk strata, despite stroke risk being a
continuum. Also, many studies have shown that
high-risk patients were undertreated with warfarin
and that those patients defined as ‘low risk’ using
the CHADS2 score were not low risk, with a stroke
rate as high as 3.2%/year [14].
The availability of the non-VKA oral anticoagulants
[(NOACs) previously referred to as new or novel OACs
[15]] and the recognition of the need for high-quality
anticoagulation control with a VKA [with average time
in therapeutic range (TTR) >70% [16]] has changed
the approach. The NOACs offer many advantages,
but some unanswered questions and gaps in trans-
lation to clinical practice remain [17, 18].
All the major guidelines [European, American and
National Institute for Health and Care Excellence
(NICE)] now recommend use of the CHA2DS2-VASc
score for stroke risk stratification [19–21]. The
CHA2DS2-VASc score extends the earlier CHADS2
score by including ‘non-CHADS2’ risk factors such
as age 65–74 years, vascular disease and female
sex [22] (Table 1). The CHA2DS2-VASc score out-
performs the CHADS2 score in being able to
discriminate ‘low-risk’ patients, who would not
derive any benefit from antithrombotic therapy
[23].
With the use of antithrombotic therapy, bleeding
risks as part of tailored therapy and decision-
making also have to be considered. Stroke and
bleeding risks track each other, but it would be
important to assess the patient’s potential risk of
bleeding at clinical review and follow-up [24]. The
HAS-BLED score has been recommended as an
easy, validated bleeding risk assessment tool [25]
(Table 1 for definition). The HAS-BLED score has
been shown to be as good as, and possibly better
than, other bleeding risk scores in predicting
clinically relevant bleeding events [26, 27]. A high
HAS-BLED score is not a reason to withhold OAC
treatment but to ‘flag up’ patients potentially at
risk of bleeding for more careful review and follow-
up and, importantly, to help identify and correct
potentially reversible risk factors for bleeding, such
as uncontrolled hypertension (the H in HAS-
BLED), labile international normalized ratios
[(INRs) if a warfarin user; the L in HAS-BLED],
alcohol excess or concomitant antiplatelet use in
an anticoagulated patient.
ª 2016 The Association for the Publication of the Journal of Internal Medicine 469
Journal of Internal Medicine, 2016, 279; 467–476
 G. Y. H. Lip et al.
Table 1 Stroke and bleeding risk stratification with the CHA2DS2-VASc and HAS-BLED schemas
CHA2DS2-VASc
Congestive heart failure/LV dysfunction
Hypertension
Age ≥75 years
Diabetes mellitus
Stroke/TIA/TE
Vascular disease (prior MI, PAD
or aortic plaque)
Age 65–74 years
Sex category (i.e. female)
Maximum score
BP, blood pressure; LV, left ventricular; MI, myocardial infarction; NSAID, nonsteroidal anti-inflammatory drug; PAD,
pulmonary artery disease; TE, thromboembolism; TIA, transient ischaemic attack; INR, international normalized ratio.
A tailored approach to stroke prevention is shown
in Fig. 1, with the use of the various clinical scores
to evaluate stroke risk, bleeding risk and likelihood
of successful warfarin therapy, respectively [28,
29]. The initial focus is on identification of ‘truly
low-risk’ patients with AF (step 1), that is those
patients who with a CHA2DS2-VASc score of 0
(male) or 1 (female), who do not need any
antithrombotic therapy. Subsequently (step 2),
patients with AF and ≥1 stroke risk factors can be
offered effective stroke prevention, that is oral
anticoagulation. Oral anticoagulation is given
either as a NOAC or a VKA (e.g. warfarin) with
good anticoagulation control as reflected by a TTR
of >70%. This is the approach used in the Euro-
pean [19] and NICE [21] guidelines.
Recently, whether a single risk factor [i.e.
CHA2DS2-VASc score of 1 (male) or 2 (female)]
merits oral anticoagulation has been discussed
[30, 31]. The results of a recent Swedish study [32]
suggested that ischaemic stroke rates in this
category may be too low to warrant anticoagula-
tion, but methodological issues were a concern
given that all patients who were started on OAC
therapy at any time were excluded from the study,
thus ‘conditioning on the future’ and resulting in
bias towards artificially lower event rates [30, 31].
In addition, the Swedish results are at variance
with other data from Asia and Europe [33, 34]
showing ischaemic stroke rates of 1.5–2.5%/year
with a single stroke risk factor. Indeed, in the Loire
Valley AF study it was found that OAC use was
independently associated with a better prognosis
470 ª 2016 The Association for the Publication of the Journal of Internal Medicine
Journal of Internal Medicine, 2016, 279; 467–476
Review Symposium: Tailored stroke prevention
Score HAS-BLED Score
1 Hypertension (i.e. uncontrolled BP) 1
1 Abnormal renal/liver function 1 or 2
2 Stroke 1
1 Bleeding tendency or predisposition 1
2 Labile INR (if on warfarin) 1
1 Age (e.g. >65 years, frail condition) 1
1 Drugs (e.g. concomitant aspirin or 1
NSAIDSs) or alcohol excess
1
9 9
in AF patients with a single additional stroke risk
factor [i.e. CHA2DS2-VASc score of 1 (male) or 2
(female); adjusted hazard ratio 0.59, 95% CI 0.40–
0.86, P = 0.007] [35].
A positive net clinical benefit (NCB) of OAC versus
No treatment, or OAC versus aspirin, was clearly
evident in patients with a single stroke risk factor
[i.e. CHA2DS2-VASc score of 1 (male) or 2 (female)];
by contrast, the NCB of aspirin versus no treat-
ment was neutral/negative, indicating no benefit
of aspirin even with a single stroke risk factor
[36, 37].
Thus, clinicians would need to ask themselves
whether it is worth taking the risk of exposing
patients to fatal and disabling strokes. Impor-
tantly, AF patients are also not ‘static’ in relation
to their risk profile, given that the patient popula-
tion is often elderly and having multiple comor-
bidities.
Some European healthcare systems also manage
anticoagulation control with warfarin very well,
and thus, a common question is how can we
identify those patients likely to do well on warfarin,
rather than using a blanket ‘NOAC for everyone’
policy or a ‘trial of warfarin’ approach which leaves
patients with suboptimal anticoagulation control
for the initial few months prior to a decision being
taken about whether a NOAC can be prescribed.
The SAMe-TT2R2 score [38] has recently been
introduced to help physicians make informed
decisions on those patients likely to do well on
 G. Y. H. Lip et al. Review Symposium: Tailored stroke prevention

Fig. 1 A tailored approach to assessment and stroke prevention in atrial fibrillation (AF) with the use of the CHA2DS2VASc,
HAS-BLED and SAMeTT2R2 scores to evaluate stroke risk, bleeding risk and likelihood of successful warfarin therapy,
respectively. Non-vitamin K antagonist oral anticoagulants (NOACs) may be considered where the SAMeTT2R2 score
predicts poor control of anticoagulation with warfarin. VKA, vitamin K antagonist; INR, international normalized ratio;
NSAID, nonsteroidal anti-inflammatory drug; OAC, oral anticoagulant; and TTR, time in therapeutic range. Reproduced from
Shields and Lip, with permission [29].

warfarin (SAMe-TT2R2 score 0–2) or those who are
likely to have a poor TTR (SAMe-TT2R2 score >2)
(Table 2 for definition). The latter group would
benefit from more intense counselling, education
and follow-up [39] or, preferentially, a NOAC [40,
41]. The SAMe-TT2R2 score has been validated in
multiple independent cohorts [42, 43], and a high
score has been related to labile INRs, and the
associated sequelae of thromboembolism, serious
bleeding and mortality [44, 45].
What aspects of the patient profile should be
considered? Numerous patient factors can be con-
sidered. For example, Asian patients with AF
present some additional issues with regard to
stroke prevention [46, 47]. Specifically, Asian
patients have a higher risk of intracranial
haemorrhage (ICH) and, even on warfarin, have
higher risks of stroke/systemic embolism and
major bleeding, compared with non-Asians with
AF; however, Asian patients show impressive
reductions in ICH related to the use of NOACs
[47]. Whilst on warfarin, a poor average TTR
amongst Asians is common, and may contribute
to the high event rates. Many reasons for the poor
TTR have been discussed but include the tendency
for physicians to aim towards a lower INR range,
use of herbal medicines and poor compliance.
Renal function is also an important consideration,
as illustrated by a recent consensus document
from the European Heart Rhythm Association

ª 2016 The Association for the Publication of the Journal of Internal Medicine 471
Journal of Internal Medicine, 2016, 279; 467–476
 G. Y. H. Lip et al.
Table 2 The SAMe-TT2R2 score for assisting with decision-
making for use of oral anticoagulants
Acronym Definitions
S Sex (female)
A Age (less than 60 years)
M Medical historya
e interpatient variability in responsiveness and min-
T Treatment (interacting drugs
e.g. amiodarone for rhythm control)
T Tobacco use (within 2 years)
R Race (non-Caucasian)
Maximum points
a
Two of the following: hypertension, diabetes mellitus,
coronary artery disease/myocardial infarction, pul-
monary artery disease, cardiac heart failure, previous
stroke, pulmonary disease, hepatic or renal disease.
(EHRA) [48]. AF patients with chronic kidney
disease represent a high-risk group for stroke,
death, myocardial infarction and major bleeding
[49, 50]. Renal impairment does not independently
add to the CHA2DS2-VASc score for stroke predic-
tion [51, 52].
Beyond the CHA2DS2-VASc score, there are many
potential additional stroke risk factors, whether
clinical or biomarker based, that have been asso-
ciated with elevated risks of stroke and throm-
boembolism. It is clear that the term biomarkers
could refer to ‘biological markers’ whether blood,
urine, imaging (cardiac or cerebral) or clinical [53].
Blood biomarkers have included indices of coagu-
lation, platelets, inflammation or extracellular
matrix turnover, as well as various genotypes.
Many biomarkers are nonspecific for decision-
making regarding stroke and bleeding risks, being
predictive of both these risks. The prevalence,
accessibility, ease of measurement and degree of
impact of various biomarkers on thromboembolic
risk also differ greatly, which results in very
different utility in clinical practice.
Indeed, adding multiple biomarkers may help
improve prediction of ‘high risk’ but would confer
additional costs, time delay or the disadvantage of
adding substantial complexity, expense and lack of
practicality, which would be a disadvantage espe-
cially where quick treatment decisions are needed
in busy clinics or wards. Thus, rather than the
obsession to identify ‘high-risk’ patients, the focus
472 ª 2016 The Association for the Publication of the Journal of Internal Medicine
Journal of Internal Medicine, 2016, 279; 467–476
Review Symposium: Tailored stroke prevention
should be on the initial identification of low-risk
patients, following which effective stroke preven-
tion can be offered to those with ≥1 additional
Points
stroke risk factors.
1
1 What about genetic factors? Warfarin metabolism
1 genotypes have been proposed to overcome the
1 imize the requirement for INR dose adjustment.
Results from randomized trials of genotype-guided
warfarin dosing have been disappointing [54, 55]. A
2 substudy of the Effective Anticoagulation With
2 Factor Xa Next Generation in Atrial Fibrillation
8 (ENGAGE – AF TIMI – 48) trial found that CYP2C9
and VKORC1 genotypes identified patients who
were more likely to experience early bleeding with
warfarin and who derived a greater early safety
benefit from edoxaban compared with warfarin for
stroke prevention [56].
Optimal periprocedural use of anticoagulation therapy: ablation,
cardioversion and device surgery
Given that many patients with AF are being treated
with OACs, a practical consideration is what to do
when procedures need to be performed, for exam-
ple ablation, cardioversion or device implantation.
This has been addressed recently in a consensus
document from the EHRA [57].
In relation to ablation, many centres now perform
the procedure whilst the patient is on therapeutic
warfarin (INR 2–3), with good outcomes. Observa-
tional data suggest that there are additional risks
of bleeding or thromboembolism when ablation is
performed with interrupted warfarin and bridging
[58]. In the Role of Coumadin in Preventing Throm-
boembolism in Atrial Fibrillation (AF) Patients
Undergoing Catheter Ablation (COMPARE) ran-
domized trial, thromboembolism risks were higher
with interrupted warfarin compared with a strategy
of continuous warfarin [59]. The low risk of peri-
cardial effusion is mitigated by the ability to
‘reverse’ the anticoagulation effect of warfarin by
administration of vitamin K and fresh frozen
plasma, or by other nonspecific reversal strategies.
With the availability of the NOACs, how best to
manage anticoagulation peri-ablation in patients
taking these drugs has been debated. Results from
cohort studies and meta-analyses suggest that
periprocedural anticoagulation with NOACs is as
safe and effective as with warfarin [60]. However,
some centres continue with uninterrupted NOACs,
 G. Y. H. Lip et al.
whereas others stop the drug 24 h beforehand, and
administer heparin bridging. Ongoing randomized
trials with the NOACs will provide some additional
data on the optimal strategy for these patients.
For cardioversion, current guidelines recommend
therapeutic anticoagulation (whether warfarin with
an INR of 2–3, or a NOAC) for a minimum of
3 weeks prior to elective cardioversion, and con-
tinuation of anticoagulation for a minimum of
4 weeks postcardioversion; however, in the pres-
ence of stroke risk factors, long-term anticoagula-
tion should be considered even after the apparent
restoration of sinus rhythm [19]. With a transoe-
sphageal echocardiography-guided strategy, pre-
existing left atrial appendage thrombus is
excluded, following which cardioversion can be
performed and oral anticoagulation (e.g. a NOAC,
which has a rapid onset of action) can be admin-
istered for a minimum of 4 weeks. Again, in the
presence of stroke risk factors, long-term antico-
agulation should be considered even following the
apparent restoration of sinus rhythm.
Data regarding pericardioversion anticoagulation
with the NOACs were obtained from a subgroup of
patients from the large Phase III trials with dabi-
gatran and apixaban [61, 62]. For rivaroxaban, few
patients underwent cardioversion (or ablation) in
the ROCKET-AF trial, but the X-VERT trial showed
that there were no significant differences in throm-
boembolism or bleeding with rivaroxaban com-
pared with warfarin; however, fewer patients in the
rivaroxaban arm experienced delays in undergoing
cardioversion [63].
In the situation of device implantation, the
accepted option is to perform the procedure with
uninterrupted warfarin, rather than interrupted
warfarin with heparin bridging. The latter strategy
is associated with more bleeding and thrombotic
events, as was shown in the Bridge or Continue
Coumadin for Device Surgery Randomized Con-
trolled Trial (BRUISE CONTROL) trial [64]. Until
additional data are available, NOACs should prob-
ably be temporarily discontinued without heparin
bridging for all device surgery.
The optimal periprocedural use of anticoagulation
therapy in the setting of ablation, cardioversion
and device surgery has been addressed by a new
EHRA consensus document, endorsed by the
Working Group on Thrombosis, Heart Rhythm
Society and Asia-Pacific Heart Rhythm Society [57].
Review Symposium: Tailored stroke prevention
The patient with acute coronary syndrome: rationale for individual
anticoagulation therapy and stent preference
In the management cascade of AF, stroke preven-
tion is the main priority. Because approximately
25–30% of AF patients have associated coronary
artery disease, some may present with an acute
coronary syndrome (ACS) and/or require percuta-
neous coronary intervention and stenting. Hence,
the dilemma is how to balance stroke prevention
(with OACs) with preventing recurrent cardiac
ischaemia (if ACS, with antiplatelet agents), avoid-
ing stent thrombosis (with antiplatelet agents) and
managing the risk of serious bleeding (with OACs
combined with antiplatelet drugs).
In 2014, the joint European consensus document
endorsed by the Heart Rhythm Society and Asia-
Pacific Heart Rhythm Society was published, pro-
viding detailed consensus recommendations on
managing these complex patients [65]. In general,
a period of triple therapy (OAC, aspirin and clopi-
dogrel) is needed, followed by an OAC and single
antiplatelet drug (preferably clopidogrel) then,
when the patient is stable, an OAC alone. There
is a preference towards using third-generation
drug-eluting stents, and to keep the duration of
triple therapy as short as possible, balancing
stroke and bleeding risks using the CHA2DS2-
VASc and HAS-BLED scores. In stable vascular
disease, OAC monotherapy would suffice, as com-
bination OAC plus antiplatelet therapy leads to a
higher risk of bleeding without any significant
reduction in cardiovascular events or thromboem-
bolism. The OAC can be either a VKA (e.g. warfarin)
with a TTR of >70%, or a NOAC. The latter should
be given in the lower tested dose used for AF stroke
prevention, for example dabigatran 110 mg twice
daily (bid), rivaroxaban 15 mg and apixaban
2.5 mg bid [65].
Conclusions
Screening provides opportunities for identification
of AF and improving stroke prevention in patients
with this common arrhythmia. The harder one
looks, the more likely it is that AF will be found.
Modern AF stroke prevention requires a tailored
treatment strategy. Biomarkers and genetic factors
have been proposed to help identify ‘high-risk’
patients to be targeted for oral anticoagulation,
but ultimately their use must be balanced against
the simplicity and practicality for routine applica-
tion for everyday use.
ª 2016 The Association for the Publication of the Journal of Internal Medicine 473
Journal of Internal Medicine, 2016, 279; 467–476
 G. Y. H. Lip et al.
A clinically focused tailored approach to assessment
and stroke prevention in AF with the use of the
CHA2DS2VASc, HAS-BLED and SAMeTT2R2 scores
to evaluate stroke risk, bleeding risk and likelihood
of successful warfarin therapy, respectively, is
advocated. Finally, patient values and preferences
should be considered, as advocated in a recent
consensus document from the EHRA [66]. Manage-
ment of the patient with AF can only improve.
Conflict of interest statement
Prof GYH Lip has been a member of various
committees/reviewing bodies for guidelines and
position statements from European Society of
Cardiology, EHRA, NICE, and others; a member
of steering committees for various Phase II and III
studies, and health economics and outcomes
research; an investigator in various clinical trials
of cardiovascular disease, including antithrom-
botic therapies in AF, ACS, lipid disorders, and
others; a consultant for Bayer/Jensen J&J, Astel-
las, Merck, Sanofi, BMS/Pfizer, Biotronik, Medtro-
nic, Portola, Boehringer Ingelheim, Microlife and
Daiichi-Sankyo; and a speaker for Bayer, BMS/
Pfizer, Medtronic, Boehringer Ingelheim, Microlife,
Roche and Daiichi-Sankyo. Prof G Boriani received
speaker fees from Boehringer, Boston, Medtronic,
St. Jude.
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europace/euv233 [Epub ahead of print].
Correspondence: Prof G. Y. H. Lip, University of Birmingham
Centre for Cardiovascular Sciences, City Hospital, Birmingham,
UK.
(fax: +44 121 5075503; e-mail: g.y.h.lip@bham.ac.uk).