Guidelines

2007 Guidelines for the Management of Arterial Hypertension

The Task Force for the Management of Arterial Hypertension of the European Society
of Hypertension (ESH) and of the European Society of Cardiology (ESC)
Authors/Task Force Members: Giuseppe Mancia
Mancia,, Co-
Co-Chairperson (Italy), Guy de Backer, Co-
Co-Chairperson (Belgium), Anna
Dominiczak (UK), Renata Cifkova (Czech Republic), Robert Fagard (Belgium), Giuseppe Germano (Italy), Guido Grassi
(Italy), Anthony M. Heagerty (UK), Sverre E. Kjeldsen (Norway), Stephane Laurent (France), Krzysztof Narkiewicz
(Poland), Luis Ruilope (Spain), Andrzej Rynkiewicz (Poland), Roland E. Schmieder (Germany), Harry A.J. Struijker Boudier
(Netherlands), Alberto Zanchetti (Italy)
ESC Committee for Practice Guidelines (CPG): Alec Vahanian Vahanian,, Chairperson (France), John Camm (United Kingdom), Raffaele De Caterina
(Italy), Veronica Dean (France), Kenneth Dickstein (Norway), Gerasimos Filippatos (Greece), Christian Funck Funck--Brentano (France), Irene
Hellemans (Netherlands), Steen Dalby Kristensen (Denmark), Keith McGregor (France), Udo Sechtem (Germany), Sigmund Silber (Germany),
Michal Tendera (Poland), Petr Widimsky (Czech Republic), Jose´ Jose´ Luis Zamorano (Spain)
ESH Scientific Council: Sverre E. Kjeldsen
Kjeldsen,, President (Norway), Serap Erdine
Erdine,, Vice-
Vice -President (Turkey), Krzysztof Narkiewicz
Narkiewicz,, Secretary
(Poland), Wolfgang Kiowski
Kiowski,, Treasurer (Switzerland), Enrico Agabiti
Agabiti--Rosei (Italy), Ettore Ambrosioni (Italy), Renata Cifkova (Czech Republic),
Anna Dominiczak (United Kingdom), Robert Fagard (Belgium), Anthony M. Heagerty Heagerty,, Stephane Laurent (France), Lars H. Lindholm (Sweden),
Giuseppe Mancia (Italy), Athanasios Manolis (Greece), Peter M. Nilsson (Sweden), Josep Redon (Spain), Roland E. Schmieder (Germany),
Harry A.J. Struijker
Struijker-- Boudier (The Netherlands), Margus Viigimaa (Estonia)
Document Reviewers: Gerasimos Filippatos (CPG Review Coordinator) (Greece), Stamatis Adamopoulos (Greece), Enrico Agabiti Agabiti--Rosei
(Italy), Ettore Ambrosioni (Italy), Vicente Bertomeu (Spain), Denis Clement (Belgium), Serap Erdine (Turkey), Csaba Farsang (Hungary), Dan
Gaita (Romania), Wolfgang Kiowski (Switzerland), Gregory Lip (UK), Jean- Jean- Michel Mallion (France), Athanasios J. Manolis (Greece), Peter M.
Nilsson (Sweden), Eoin O’Brien (Ireland), Piotr Ponikowski (Poland), Josep Redon (Spain), Frank Ruschitzka (Switzerland), Juan Tamargo
(Spain), Pieter van Zwieten (Netherlands), Margus Viigimaa (Estonia), Bernard Waeber (Switzerland), Bryan Williams (UK), Jose Luis
Zamorano (Spain)

Journal of Hypertension 2007, 25:1105–

25:1105–1187
Eur Heart J 2007, 28:1462-
28:1462-1536

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 2007
2007 ESH/ESC
ESH/ESC Guidelines
Guidelines
1. INTRODUCTION AND PURPOSES 4.4 Event based trials comparing different active treatments 7. THERAPEUTIC APPROACHES IN SPECIAL
2. DEFINITION AND CLASSIFICATION OF 4.4.1 Calcium antagonists versus thiazide diuretics and CONDITIONS
HYPERTENSION ß- blockers 7.1 Elderly
2.1 Systolic versus diastolic and pulse pressure 4.4.2 ACE inhibitors versus thiazide diuretics and 7.2 Diabetes mellitus
2.2 Classification of hypertension ß- blockers 7.3 Cerebrovascular disease
2.3 Total cardiovascular risk 4.4.3 ACE inhibitors versus calcium antagonists 7.3.1 Stroke and transient ischemic attacks
2.3.1 Concept 4.4.4 Angiotensin receptor antagonists versus other 7.3.2 Cognitive dysfunction and dementia
2.3.2 Assessment drugs 7.4 Coronary heart disease and heart failure
2.3.3 Limitations 4.4.5 Trials with ß-
ß- blockers 7.5 Atrial fibrillation
3. DIAGNOSTIC EVALUATION 4.4.6 Conclusions 7.6 Renal disease
3.1 Blood pressure measurement 4.5 Randomized trials based on intermediate end-
end- points 7.7 Hypertension in women
3.1.1 Office or clinic blood pressure 4.5.1 Heart 7.7.1 Oral contraceptives
3.1.2 Ambulatory blood pressure 4.5.2 Arterial wall and atherosclerosis 7.7.2 Hormone replacement therapy
3.1.3 Home blood pressure 4.5.3 Brain and cognitive function 7.7.3 Hypertension in pregnancy
3.1.4 Isolated office or white coat hypertension 4.5.4 Renal function and disease 7.8 Metabolic syndrome
3.1.5 Isolated ambulatory or masked hypertension 4.5.5 New onset diabetes 7.9 Resistant hypertension
3.1.6 Blood pressure during exercise and laboratory 5. THERAPEUTIC APPROACH 7.10 Hypertensive emergencies
stress 5.1 When to initiate antihypertensive treatment 7.11 Malignant hypertension
3.1.7 Central blood pressure 5.2 Goal of treatment 8. TREATMENT OF ASSOCIATED RISK
3.2 Family and clinical history 5.2.1 Blood pressure target in the general hypertensive FACTORS
3.3 Physical examination population 8.1 Lipid lowering agents
3.4 Laboratory investigation 5.2.2 Blood pressure target in diabetic and very high or 8.2 Antiplatelet therapies
3.5 Genetic analysis high risk patients 8.3 Glycaemic control
3.6 Searching for subclinical organ damage 5.2.3 Home and ambulatory blood pressure targets 9. SCREENING AND TREATMENT OF
3.6.1 Heart 5.2.4 Conclusions SECONDARY FORMS OF HYPERTENSION
3.6.2 Blood vessels 5.3 Cost-
Cost-effectiveness of antihypertensive treatment 9.1 Renal parenchymal disease
3.6.3 Kidney 6. TREATMENT STRATEGIES 9.2 Renovascular hypertension
3.6.4 Fundoscopy 6.1 Lifestyle changes 9.3 Phaeochromocytoma
3.6.5 Brain 6.1.1 Smoking cessation 9.4 Primary aldosteronism
4. EVIDENCE FOR THERAPEUTIC MANAGEMENT 6.1.2 Moderation of alcohol consumption 9.5 Cushing’s syndrome
OF HYPERTENSION 6.1.3 Sodium restriction 9.6 Obstructive sleep apnoea
4.1 Introduction 6.1.4 Other dietary changes 9.7 Coarctation of aorta
4.2 Event based trials comparing active treatment to 6.1.5 Weight reduction 9.8 Drug-
Drug-induced hypertension
placebo 6.1.6 Physical exercise 10. FOLLOW
FOLLOW-- UP
4.3 Event based trials comparing more or less intense 6.2 Pharmacological Therapy 11. IMPLEMENTATION OF GUIDELINES
blood pressure lowering 6.2.1 Choice of antihypertensive drugs APPENDIX
6.2.2 Monotherapy REFERENCES
6.2.3 Combination treatment

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 2007
2007 ESH/ESC
ESH/ESC Guidelines
Guidelines
Benefits
Benefits of
of Antihypertensive
Antihypertensive Treatment
Treatment

Significant reductions in CV morbidity / mortality

Benefit at older ages, including ISH
Proportional CV risk reduction in men/women
Benefit across various ethnic groups
- Caucasians
- Asians
- Blacks
Major reductions in cause-specific events
- Stroke (-30 to -40%)
- CHD (-20%)
- CHF (> -40%)
11852 M
 Metanalysis
Metanalysis of
of Trials
Trials Comparing
Comparing Different
Different Treatments
Treatments or
or
Treatment
Treatment vs vs Placebo
Placebo in
in Hypertension
Hypertension

Relative risk of outcome event

1.50

1.25
Stroke
1.00
CHD
0.75

0.50

0.25
-10 -8 -6 -4 -2 0 2 4
SBP difference between randomized groups (mmHg)

11688 M BP Trialists’ Coll Group, Lancet 2003

 VALUE: Analysis of Results Based on
BP Control at 6 Months
Patients Treated With Valsartan Patients Treated With Amlodipine
Odds Ratio Odds Ratio
Fatal/Non-fatal cardiac ** 0.76 ** 0.73
(0.66–0.88) (0.63–0.85)
events
Fatal/Non-fatal 0.60 0.50
** (0.48–0.74) **
stroke (0.39–0.64)

** 0.79 ** 0.79
All-cause death (0.69–0.91) (0.69–0.92)
0.83 0.91
Myocardial infarction (0.66–1.03) (0.71–1.17)
Heart failure ** 0.62 ** 0.64
(0.50–0.77) (0.52–0.79)
hospitalisations
0.4 0.6 0.8 1.0 1.2 0.4 0.6 0.8 1.0 1.2
Controlled Non-controlled Controlled Non-controlled
patients* patients patients* patients
(n = 5253) (n = 2396) (n = 5502) (n = 2094)
Hazard Ratio 95% CI Hazard Ratio 95% CI
*SBP < 140 mmHg at 6 months.
**P < 0.01.
Weber MA et al. Lancet. 2004;363:2047–49.
 2007
2007ESH/ESC
ESH/ESC Guidelines
Guidelines
BP
BP Threshold
Threshold // Target
Target in
in the
the General
General Hypertensive
Hypertensive Population
Population

BP threshold BP target

140/90 mmHg < 140/90 mmHg

(and lower values
if tolerated)

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 Evidence
Evidence on
on Greater
Greater CV
CV Protection
Protection by
by Tighter
Tighter BP
BP Control
Control

UKPDS IDNT HOT ABCD ADVANCE Meta--analysis

Meta

Diabetes

Multiple INVEST
trials Renal More intense BP ¯
EUROPA
dysfunction / Lower BP target CAD
Meta-
Meta- CAMELOT
proteinuria Lower BP threshold
analyses
HOPE

Previous stroke / TIA

PROGRESS PATS

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 On-treatment BP
On-treatment BP in
in Recent
Recent Trials
Trials
CVD ¯ ¯ ¯ ¯ ®
PROGRESS EUROPA CAMELOT ABCD PEACE
140
128 128 129
127
124

120
mmHg

100

80
78 76
75 75 74

60
Pts: CerVD CAD CAD DM CAD

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 Trials
Trials Showing
Showing CV CV Protection
Protection by
by Treatment
Treatment
at
at Initial
Initial BP
BP << 140/90
140/90 mmHg
mmHg

Trial Treatment

HOPE (High CV risk / CAD) ACEI

ABCD (Diabetes) ACEI / CA
CAMELOT (CAD) CA
PROGRESS (Cerebrov. D) ACEI / D
PATS (Cerebrov. D) ACEI / D
EUROPA (CAD) ACEI
ADVANCE (Diabetes) ACEI / D
JIKEI (High CV risk) ARB
PEACE (CAD) ACEI
No protection
ACTION (CAD) CA

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 Trials
Trials Showing
Showing CV CV Protection
Protection by
by Treatment
Treatment
at
at Initial
Initial BP
BP << 140/90
140/90 mmHg
mmHg

Trial Treatment

HOPE (High CV risk / CAD) ACEI

ABCD (Diabetes) ACEI / CA
CAMELOT (CAD) CA
PROGRESS (Cerebrov. D) ACEI / D
PATS (Cerebrov. D) ACEI / D
EUROPA (CAD) ACEI
ADVANCE (Diabetes) ACEI / D
Jikei (High CV risk) ARB

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 2007
2007ESH/ESC
ESH/ESC Guidelines
Guidelines
BP
BP Thresholds
Thresholds // Targets
Targets ((mmHg)
mmHg)

General HT population High risk patients

(CAD/Cerebrovasc. disease/
Diabetes/Renal dysfunction)

Threshold 140/90 130/85

Target < 140/90 < 130/80

Concept of flexible threshold/target

for treatment in relation to total CV risk
11854 M
 Stratification
Stratification of
of CV
CV Risk
Risk in
in Four
Four Categories
Categories
Blood Pressure (mmHg)

Other Risk Factors, Normal High Normal Grade 1 HT Grade 2 HT Grade 3 HT

OD SBP 120-
120-129 SBP 130-
130-139 SBP 140-
140-159 SBP 160-
160-179 SBP 180
or Disease or DBP 80-
80-84 or DBP 85-
85-89 or DBP 90-
90-99 or DBP 100-
100-109 or DBP 110

Average Average Low Moderate High

No other risk factors
risk risk added risk added risk added risk

Low Low Moderate Moderate Very high

1-2 risk factors
added risk added risk added risk added risk added risk

3 or more Risk Factors, Moderate High High High Very high

MS, OD or Diabetes added risk added risk added risk added risk added risk

Established CV Very high Very high Very high Very high Very high
or renal disease added risk added risk added risk added risk added risk
SBP: systolic blood pressure; DBP: diastolic blood pressure; CV: cardiovascular
cardiovascular;; HT: hypertension
hypertension.. Low, moderate, high, very high risa refer to 10year risk of a CV fatal or non
non--fatal event
event..
The term “added
added”” indicates that in all categories risk is greater than average
average.. OD: subclinical organ damage; MS: metabolic syndrome
syndrome..

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 Risk
Risk Reclassification
Reclassification in
in APROS
APROS Study
Study

100 Risk:
% High
80 Medium
53.2%
Low
60 81.3%

40
35.7%

20
18.7%
11.1%
0 ** After
After ecocardiogram
ecocardiogram ++
Initial Final * carotid
carotid ultrasonography
ultrasonography

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Cuspidi et al., J Hypertens 2002; 20: 1307-1315
 ESH/ESC
ESH/ESC Guidelines
Guidelines and
and Search
Search for
for Subclinical
Subclinical Organ
Organ Damage
Damage

2003 - SCr (> 1.4-1.5 mg/dl) LVH (Echo)

GLs EKG † CA thickening / plaques
MA

Search for
multiorgan OD
Routine Recommended OD assessed before
and during T

2007 - SCr (> 1.4-1.5 mg/dl) LVH (Echo)

GLs ¯ eCrCl / GFR Concentric LVH
MA LA enlargement
EKG † CA thickening / plaques
Ankle/Brachial ratio
Arterial stiffening (PWV)*
* Depending on availability / also shown by high SBP / low DBP
† LVH / MI-
MI-ischemia / Arrhythmias

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 2007
2007 ESH/ESC
ESH/ESC Guidelines: Initiation
Guidelines: Initiation of
of Antihypertensive
Antihypertensive Treatment
Treatment
Blood Pressure (mmHg)
Normal High Normal Grade 1 HT Grade 2 HT Grade 3 HT
Other risk factors SBP 120-
120-129 SBP 130-
130-139 SBP 140-
140-159 SBP 160-
160-179 SBP 180
OD or disease or or or or or
DBP 80-
80-84 DBP 85-
85-89 DBP 90-
90-99 DBP 100-
100 -109 DBP 110

Lifestyle changes for

Lifestyle changes for Lifestyle changes
several
several months then +
No other risk factors No BP intervention No BP intervention weeks then drug
drug treatment if Immediate drug
treatment if BP
BP uncontrolled treatment
uncontrolled
Lifestyle changes for Lifestyle changes for
Lifestyle changes
several several
+
1-2 risk factors Lifestyle changes Lifestyle changes weeks then drug weeks then drug
Immediate drug
treatment if BP treatment if BP
treatment
uncontrolled uncontrolled
Lifestyle changes
3 Risk Factors,
Lifestyle changes and consider drug Lifestyle changes
MS or OD Lifestyle changes Lifestyle changes
treatment +
+ +
Immediate drug
Lifestyle changes + Drug treatment Drug treatment
Lifestyle changes treatment
Diabetes Drug treatment

Lifestyle changes Lifestyle changes Lifestyle changes Lifestyle changes Lifestyle changes
EstablishedCV
Established CVor + + + + +
orrenal
renal disease
disease Immediate drug Immediate drug Immediate drug Immediate drug Immediate drug
treatment treatment treatment treatment treatment

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 2007
2007 ESH/ESC
ESH/ESC Guidelines
Guidelines
Lifestyle
Lifestyle Changes
Changes

In all patients to ¯ BP / CV risk / n° /doses of drugs

Also in patients with high-normal BP and additional
risk factors (¯ new onset HT)
Lifestyle recommendations not to be given as lip service,
but instituted with adequate behavioural / expert
support and periodical reinforcement

11768 M
 Reduction
Reduction in
in CV
CV Events
Events by
by Antihypertensive
Antihypertensive Treatment
Treatment
D/BB (vs PL) ACEI (vs PL)
D BP -10
10--12/
12/--5-6 -5/
5/--2
(mmHg) CVD CHD Stroke CVD CHD Stroke
0 0

-10 -10

-20 -16 -20

-21 -20
* -22
-30 * -30
* * -28

-40 -39
-40 *
% %
CA (vs PL) * ARB ( vs others)
D BP -8/
8/--4 -3/
3/--2
(mmHg) CVD CHD Stroke CVD CHD Stroke
0 0
-4
-10 -10
-10
-20 -18 -20 * -21
-22
-30 * * -30 *
-40 -38 -40
% * %

11848 M * Statistically significant BPLTTG, Arch Int Med 2005

 Major
Major CVD
CVD with
with ACE -I vs
ACE-I vsD/BB
D/BB vs
vsCA
CA
Favours Favours
D BP (mmHg) First Second RR (95% CI) I2 (%)

ACE-I vs D/BB
Diabetes -0.5 / 0.1 0.90 (0.74-1.11) 55
No diabetes 0.6 / 0.1 1.04 (0.98-1.10) 0
Overall p homog = 0.19

CA vs D/BB
Diabetes 0.7 / -0.6 0.95 (0.82-1.10) 0
No diabetes 1.4 / -0.2 1.04 (0.98-1.10) 0
Overall p homog = 0.82

ACE-I vs CA
Diabetes 0.4 / 1.2 0.92 (0.79-1.07) 0
No diabetes 0.4 / 0.8 0.99 (0.92-1.07) 0
Overall p homog = 0.37

0.25 0.5 1 2
Risk Ratio

8776 M BP Trialists’ Coll. Group, Arch Int Med 2005

 2007
2007 ESH/ESC
ESH/ESC Guidelines
Guidelines
Choice
Choice of
of Antihypertensive
Antihypertensive Drugs
Drugs

Main benefits due to BP ¯ per se

D / CA / ACEI / ARB / BB all suitable for
initiation/maintenance of antihypertensive treatment
Because in many patients more than one drug needed
(for life) emphasis on 1st drug often futile

11820 M
 Rate
Rate of
of Mono
Mono // Combination
Combination Therapy
Therapy in
in ASCOT
ASCOT

100
91.4
85.4

80

60
Monotherapy
%
Combination therapy
40

20 14.6
8.6

0
Atenolol Amlodipine

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 2007
2007 ESH/ESC
ESH/ESC Guidelines
Guidelines
Monotherapy
Monotherapy versus
versus Combination
Combination Therapy
Therapy Strategies
Strategies
Mild BP elevation Choose between
Marked BP elevation
Low/moderate
Low /moderate CV High/very
High/ very CV high
risk risk
Conventional BP Lower BP target
target

Single agent Two-- drug combination

Two
at low dose at low dose

If goal BP not achieved

Previous agent Switch to different agent Previous combination Add a third drug
at full dose at low dose at full dose at low dose

If goal BP not achieved

Two-to
Two- to--three drug Full dose Two--three drug combination
Two
combination at full dose monotherapy at full doses

11659a M
 2007
2007 ESH/ESC
ESH/ESC Guidelines
Guidelines
Choice
Choice of
of Antihypertensive
Antihypertensive Drugs
Drugs ((to
to be
be used
used alone
alone or
or in
in combination
combination))

Previous patient’s experience with drug class

Effect of drugs on CV risk factors
Presence / absence of OD / CVD / KD / DM
clear D between drugs
Other disorders limiting particular drug use
Cost of drugs
24h BP coverage
Once-a-day administration
Continuing attention to side effects ® D between drugs
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 2007
2007 ESH/ESC
ESH/ESC Guidelines
Guidelines
Preferred
Preferred Drugs
Drugs
ISH (elderly) ® D / CA
MS ® ACEI / ARB / CA
Condition DM ® ACEI / ARB
Pregnancy ® CA / MD / BB
Blacks ® D / CA

LVH ® ACEI / CA / ARB

Asympt. atherosclerosis ® CA / ACEI
Subclinical OD MA ® ACEI / ARB
Renal dysfunction ® ACEI / ARB

Previous stroke ® any BP lowering agent

Previous MI ® BB / ACEI / ARB
Angina pectoris ® BB / CA
CHF ® D / BB / ACEI / ARB / antialdo agents
Clinical Event AF (recurrent) ® ARB / ACEI
AF (permanent) ® BB / nonDHCA
ESRF/proteinuria ® ACEI / ARB / loop D
PAD ® CA

11813 M
 Goals
Goals of
of Antihypertensive
Antihypertensive Treatment
Treatment

BP ¯ LVH
No unfavourable TOD regression / Arterial thickening / plaques
lipid effects prevention Proteinuria / microalbuminuria
Arterial stiffness
Arteriolar remodelling

NOD prevention ESRF ¯ Reduced GFR / - SCr

Endothelial dysfunction
HT prevention Arteriolar remodelling

AF prevention Coronary Ca++

Cerebral lacunae / WMLs
CAD / MI ¯
Stroke ¯ Retinopathy
CHF ¯ Cardiac fibrosis (collagen markers
markers))
Cognitive dysfunction / Dementia

10608 M
 Kaplan-Meier Plot
Kaplan-Meier Plot for
for the
the Composite
Composite End
End Point
Point
by
by AUCR
AUCR Categories
Categories

0.20

High B / high yr 1
composite end point

0.15
Fraction suffering

High B / low yr 1
0.10
Low B / high yr 1

Low B / low yr 1
0.05

0.00
0 10 20 30 40 50 60 70
Time (months)

10794 M Ibsen H et al., Hypertension 2005; 45: 198-202

 2007
2007 ESG/ESC
ESG/ESC Guidelines
Guidelines and
and Subclinical
Subclinical OD
OD -- Novelties
Novelties

More markers in routine work-up

- SCr values
- eGFR / CrCl
- MA
More measures recommended
- Detection of LVH (Echo/EKG)
- Concentric LVH
- Left atrial diameter
- CA IMT
- Arterial stiffness (PWV)
- Ankle-brachial index
Multiorgan assessment
Assessment before and during treatment
- MA ® month intervals
- LVH ® yearly intervals

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 2007
2007ESH/ESC
ESH/ESC Guidelines
Guidelines
Combinations
Combinations between
between Some
Some Classes
Classes of
of Antihypertensive
Antihypertensive Drugs
Drugs
Thiazide diuretics

ß-blockers AT1-receptor
antagonists

α -blockers
Calcium antagonists

ACE inhibitors
The preferred combinations in the general hypertensive population are represented as thick lines
lines..
The frames indicate classes of agents proven to beneficial in controlled intervention trials
trials..

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 2007
2007 ESH/ESC
ESH/ESC Guidelines
Guidelines
Combination
Combination Therapy
Therapy

More than one agent necessary to achieve BP control in the

majority of patients
A vast array of effective / well tolerated combinations available
A combination of two drugs at low doses preferred 1st step when
- initial BP in 2-3 grade range
- total CV risk high / very high

Need for more prompt BP control

Fixed combinations simplify treatment / favour compliance
In several patients combination of three or more drugs necessary
11815 M
 2007
2007 ESH/
ESH/ ESC
ESC Guidelines
Guidelines
Total
Total CV
CV Risk
Risk

Dysmetabolic risk factors / subclinical OD common in

hypertensives
All patients should be classified in relation to hypertension
grades and total CV risk
Treatment strategies depend on the initial level of risk
Total risk expressed as absolute 10-year risk of a CV event.
In younger patients treatment decision better guided by
relative risk

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