Transcript Slide 1

VBWG
Role of RAAS Modulation:
Recent Clinical Trials
• CAD
• Diabetes
• ACEIs and ARBs
Benefit of ACE inhibition in CAD
Post-MI, HF, LVEF <40%
SOLVD
SAVE
AIRE
TRACE
SOLVD
(prev)
VBWG
HOPE
High risk
EUROPA
All CAD patients
Bertrand ME. Curr Med Res Opin. 2004;20:1559-69.
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EUROPA: EUropean trial on Reduction
Of cardiac events with Perindopril in stable
coronary Artery disease
Objective:
Assess effects of the ACEI perindopril on CV risk
in a broad-spectrum population with stable CAD
and without HF
Design:
N = 12,218, age ≥18 years, with
CAD/without HF at randomization
Treatment:
Perindopril 8 mg or placebo
Follow-up:
4.2 years
Primary
outcome:
CV death, nonfatal MI, cardiac arrest
EUROPA Investigators. Lancet. 2003;362:782-8.
EUROPA: Baseline characteristics
Perindopril (%)
(n = 6110)
Placebo (%)
(n = 6108)
Female
History of CAD
– MI
– PCI
– CABG
Documented CAD
– Angiographic evidence
(stenosis >70% )
14.5
100
64.9
29.0
29.3
14.7
100
64.7
29.5
29.4
60.4
60.5
– Positive stress test
(in men w/chest pain)
History of stroke/TIA
PVD
Hypertension
Diabetes
Hypercholesterolemia
22.6
23.3
3.4
7.1
27.0
11.8
63.3
3.3
7.4
27.2
12.8
63.3
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EUROPA Investigators. Lancet. 2003;362:782-8.
EUROPA: Concomitant medications
Baseline (%)
3 Years (%)*
Platelet inhibitors
92
91
Beta-blockers
62
63
Lipid-lowering agents
58
69
Nitrates
43
NA
Calcium channel blockers
32
NA
9
NA
Diuretics
*Concomitant medications
recorded in 11,547 patients
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EUROPA Investigators. Lancet. 2003;362:782-8.
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EUROPA: Primary outcome
CV death, MI, cardiac arrest
14
RRR 20% (95% CI: 9%–29%)
AR 8.0% vs 9.9%
P = 0.0003
12
10
Primary
outcome
(%)
Placebo
Perindopril
8 mg
8
6
20%
14%
4
11%
2
P < 0.05
10%
0
P = 0.35
0
1
2
3
4
5
Time (years)
AR = absolute risk (perindopril vs placebo)
EUROPA Investigators. Lancet. 2003;362:782-8.
Fox KM. Br J Cardiol. 2004;11:195-204.
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EUROPA: Effect of ACEI on fatal/nonfatal
MI and HF hospitalizations
Fatal and nonfatal MI
10
RRR 24%
AR 5.2% vs 6.8%
P < 0.001
8
Events
(%)
HF hospitalization
RRR 39%
AR 1.0% vs 1.7%
P = 0.002
2.0
Placebo
Placebo
1.5
Perindopril
8 mg
6
Perindopril
8 mg
1.0
4
0.5
2
0
0.0
0
1
2
3
4
5
Years
AR = absolute risk (perindopril vs placebo)
0
1
2
3
4
5
Years
EUROPA Investigators. Lancet. 2003;362:782–8.
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EUROPA: Benefit of ACEI on primary
and secondary outcomes
N = 12,218
Perindopril (%)
(n = 6110)
Placebo (%)
(n = 6108)
CV mortality, MI, cardiac arrest
8.0
9.9
Total mortality, MI, UA, cardiac arrest
14.8
17.1
CV mortality, MI
7.9
9.8
Total mortality
6.1
6.9
CV mortality
3.5
4.1
Fatal/nonfatal MI
5.2
6.8
Favors
perindopril
0.5
Favors
placebo
1.0
2.0
EUROPA Investigators. Lancet. 2003;362:782-8.
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EUROPA: Benefit of ACEI on selected
secondary outcomes
N = 12,218
Perindopril (%)
(n = 6110)
Placebo (%)
(n = 6108)
Unstable angina
5.6
6.0
Cardiac arrest
0.1
0.2
Stroke
1.6
1.7
Revascularization
9.4
9.8
HF w/hospital admission
1.0
1.7
Favors
perindopril
0.5
Favors
placebo
1.0
2.0
EUROPA Investigators. Lancet. 2003;362:782-8.
VBWG
EUROPA: Consistent benefits
in predefined subgroups
N = 12,218
Primary events (%)
n
Perindopril
(n = 6110)
Placebo
(n = 6108)
Male
10,439
8.2
10.1
Female
1779
6.9
8.8
Age (years)
≤55
3948
6.5
8.9
56–65
4439
6.9
8.1
≥66
3831
10.7
12.9
0.5
Favors
perindopril
Favors
placebo
1.0
2.0
EUROPA Investigators. Lancet. 2003;362:782-8.
VBWG
EUROPA: Consistent benefits in
predefined subgroups (continued)
Primary events (%)
n
Perindopril
(n = 6110)
Placebo
(n = 6108)
Previous MI
7910
8.9
11.3
No previous MI
4299
6.4
7.3
Previous revascularization
6709
6.6
8.0
No previous revascularization
5509
9.6
12.2
Hypertension
3312
9.8
12.0
No hypertension
8906
7.3
9.1
Diabetes mellitus
1502
12.6
15.5
No diabetes mellitus
10,716
7.4
9.0
0.5
Favors
perindopril
Favors
placebo
1.0
2.0
EUROPA Investigators. Lancet. 2003;362:782-8.
VBWG
EUROPA: Benefit of perindopril was
on top of recommended medications
Primary events (%)
Favors
perindopril
Placebo
Perindopril
(n = 6110)
(n = 6108)
Lipid-lowering drug
No lipid-lowering drug
7.0
9.3
8.3
11.9
-blockers
No -blockers
7.6
8.7
10.2
9.4
Calcium channel blockers
No calcium channel blockers
9.9
7.1
11.7
9.0
0.5
Favors
placebo
1.0
2.0
EUROPA Investigators. Lancet. 2003;362:782-8.
VBWG
EUROPA: Risk reduction with perindopril
stratified by baseline systolic BP level
N = 12,218
Baseline SBP (mm Hg)
0
<120
120 to <140
140
17
18
5
10
Primary
endpoint
relative risk
reduction with
perindopril (%)
15
20
25
No interaction between
treatment and SBP:
P = 0.464
30
35
40
39
Remme WJ. Circulation. 2004;110(suppl):III-628.
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EUROPA: Systolic BP reduction during
run-in did not affect risk reduction during trial
N = 12,218
12
10
RRR 20%
n = 1841
n = 4263
n = 1804
n = 4303
8
Primary
event
(%)
RRR 18%
6
4
2
0
SBP decrease
during run-in
Placebo
Run in = 4 weeks when all patients received
perindopril 8 mg
No SBP decrease
during run-in
Perindopril
Remme WJ. Circulation. 2004;110(suppl):III-628.
EUROPA vs HOPE: Inclusion criteria
EUROPA
• Age ≥18 years
• Females: 15%
• No clinical HF
• Documented CAD including
– Previous MI, PCI/CABG
– Angiographic evidence of
CAD with/without previous
coronary event
– Positive stress test (men)
VBWG
HOPE
• Age ≥55 years
• Females: 27%
• No HF or LV dysfunction
• High-risk of CV events
with history of
– CAD, stroke, or peripheral
vascular disease
– Diabetes + ≥1 CV risk factor
(hypertension, dyslipidemia,
smoking, microalbuminuria)
HOPE patients were at higher risk than EUROPA
EUROPA Investigators. Lancet. 2003;362:782-8.
HOPE Study Investigators. N Engl J Med. 2000;342:145-53.
EUROPA vs HOPE: Study populations
Age, mean (yrs)
BP (mm Hg)
Known CAD (%)
MI (%)
PVD (%)
Stroke/TIA (%)
Revascularization (%)
Diabetes (%)
Hypertension (%)
Hypercholesterolemia (%)
EUROPA
HOPE
60
66
137/82
139/79
100
65
7
3
58
12
27
63
80
53
43
11
44
39
47
66
VBWG
EUROPA Investigators. Lancet. 2003;362:782-8.
HOPE Study Investigators. N Engl J Med. 2000;342:145-53.
VBWG
EUROPA vs HOPE: Event rates in placebo
groups reflect differences in baseline risk
3.0
2.7
2.5
Annualized
event rate
in placebo
groups
(%)
2.0
1.8
1.5
1.5
1.0
1.0
0.5
0.0
CV mortality
EUROPA
Total mortality
HOPE
80% higher annual rate of CV and total mortality in HOPE
EUROPA Investigators. Lancet. 2003;362:782-8.
HOPE Study Investigators. N Engl J Med. 2000;342:145-53.
EUROPA vs HOPE: Treatment more
intensive in EUROPA than in HOPE
VBWG
Baseline medication
100
80
92
75
62
%
57
60
39
40
28
20
0
Antiplatelet
drugs*
Betablockers
EUROPA
*Mostly aspirin
Lipidlowering
drugs
HOPE
EUROPA Investigators. Lancet. 2003;362:782-8.
HOPE Study Investigators. N Engl J Med. 2000;342:145-53.
EUROPA: Clinical implications
•
VBWG
In optimally treated CAD patients, perindopril 8 mg
significantly reduced
– CV mortality + nonfatal MI + cardiac arrest: 20%
– CV mortality + nonfatal MI: 19%
– Fatal + nonfatal MI: 24%
– Heart failure hospitalization: 39%
•
Benefits exhibited on top of recommended therapy
(aspirin, -blockers, lipid-lowering agents)
•
Benefits consistent across all predefined subgroups
•
Baseline BP and changes in BP had no significant impact on outcome
Treatment with perindopril should be considered in all
CAD patients, including patients at low risk
EUROPA Investigators. Lancet. 2003;362:782-8.
Remme WJ. Circulation. 2004;110(suppl):III-628.
VBWG
PEACE: Prevention of Events with
Angiotensin Converting Enzyme inhibition
Objective:
Assess effect of ACEI in patients
with stable CAD and normal/slightly
reduced LV function
Design:
N = 8290 randomized
Treatment:
Trandolapril 4 mg or placebo
Follow-up:
4.8 years
Primary
outcome:
CV death, nonfatal MI, CABG, PCI
PEACE Trial Investigators. N Engl J Med. 2004;351:2058-68.
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PEACE: Primary outcome
CV death, MI, CABG/PCI; N = 8290
30
4% Risk reduction
HR 0.96 (0.88–1.06)
P = 0.43
25
Placebo
Trandolapril
4 mg
20
Patients
(%)
15
10
5
0
0
1
2
3
4
5
6
Time (years)
PEACE Trial Investigators. N Engl J Med. 2004;351:2058-68.
VBWG
EUROPA vs PEACE:
Differences in compliance
3 Years
100
80
Patients
(%)
93
81
74.5
68.6
60
40
20
0
On study
ACEI
EUROPA (perindopril 8 mg)
At target
ACEI dose
PEACE (trandolapril 4 mg)
EUROPA Investigators. Lancet. 2003;362:782-8.
PEACE Trial Investigators. N Engl J Med. 2004;351:2058-68.
VBWG
ACEI trials in CAD without HF: Primary outcomes
14
12
10
% 8
6
4
2
0
EUROPA
20% Risk reduction
HR 0.80 (0.71–0.91)
P = 0.0003
Placebo
15
%
Perindopril
8 mg
1
2
3
Time (years)
4
Trandolapril
4 mg
10
2
3
Time (years)
50
4
All CV events
40
4% Risk reduction
HR 0.96 (0.88–1.06)
P = 0.43
1
QUIET
Placebo
25
%
4% Risk increase
HR 1.04 (0.89–1.22)
P = 0.6
30
20
Quinapril
20 mg
Placebo
10
5
0
Ramipril
10 mg
5
0
CV death/MI/CABG/PCI
30
15
22% Risk reduction
HR 0.78 (0.70–0.86)
P < 0.001
10
5
PEACE
20
Placebo
CV death/MI/stroke
0
0
%
HOPE
20
CV death/MI/cardiac arrest
0
1
2
3
4
Time (years)
5
6
0
1
2
Time (years)
3
HOPE Study Investigators. N Engl J Med. 2000;342:145-53.
EUROPA Investigators. Lancet. 2003;362:782-8.
Pitt B et al. Am J Cardiol. 2001;87:1058-63.
PEACE Trial Investigators. N Engl J Med. 2004;351:2058-68.
ACEI trials in CAD patients without HF:
Key baseline characteristics
EUROPA
N
Follow-up (yrs)
ACEI/dose (mg)
Age (yrs)
Men (%)
CAD/Cor rev (%)
Diabetes (%)
Hypertension (%)
Prior MI (%)
Ejection fraction (%)
PVD (%)
12,218
4.2
P-8
60
85
100/55
12
27
65
NA
7
VBWG
HOPE
PEACE
QUIET
9297
4.5
R-10
66
73
80/44
39
47
53
NA
43
8290
4.8
T-4
64
82
100/72
17
46
55
58
NA
1750
2.3
Q-20
58
82
100/100
16
47
49
59
NA
EUROPA Investigators. Lancet. 2003;362:782-8.
HOPE Study Investigators. N Engl J Med. 2000;342:145-53.
PEACE Trial Investigators. N Engl J Med. 2004;351:2058-68.
Pitt B et al. Am J Cardiol. 2001;87:1058-63.
VBWG
EUROPA, HOPE, PEACE, QUIET:
Totality of trial evidence
Event rate (%)
ACEI
All-cause death
7.5
Placebo
Favors ACEI Favors placebo
P
0.0004
8.9
0.86
MI
6.4
Stroke
2.1
Revascularization
15.5
7.7
0.0004
0.86
2.7
0.0004
0.77
16.3
0.025
0.93
0.5
0.75
1
1.25
Odds ratio
Pepine CJ, Probstfield JL. Vasc Bio Clin Pract.
CME Monograph; UF College of Medicine. 2004;6(3).
VBWG
EUROPA, HOPE, PEACE, QUIET:
CV therapies at entry/during study
EUROPA
HOPE
PEACE
QUIET
Antiplatelet agents (%)
92
76
91
73
-Blockers (%)
62
40
60
26
Lipid-lowering agents (%)
58/69*
29/49†
70
0/14†
Calcium antagonists (%)
31
47
36
0/7†
Diuretics (%)
9
15
13
NA
*at 3 yrs
†at
study end
EUROPA Investigators. Lancet. 2003;362:782-8.
HOPE Study Investigators. N Engl J Med. 2000;342:145-53.
PEACE Trial Investigators. N Engl J Med. 2004;351:2058-68.
Pitt B et al. Am J Cardiol. 2001;87:1058-63.
VBWG
ACEI outcome trials in CAD patients
without HF: BP at entry/during study
EUROPA
HOPE
PEACE
QUIET
At entry
137/82
139/79
133/78
123/74
BP in ACEI group
128/78*
136/76†
129/74‡
NA
5/2
3.3/1.2
3/1.2
NA
BP (mm Hg)
Difference in mean BP
during follow-up (ACEI
vs placebo)
*Run-in BP maintained during study
†at study end
‡at 3 years
EUROPA Investigators. Lancet. 2003;362:782-8.
HOPE Study Investigators. N Engl J Med. 2000;342:145-53.
PEACE Trial Investigators. N Engl J Med. 2004;351:2058-68.
Pitt B et al. Am J Cardiol. 2001;87:1058-63.
VBWG
HOPE, EUROPA, PEACE, QUIET:
Differences in baseline CV risk
3.0
2.0
Annualized
event rate in
placebo group
(%/yr)
1.0
2.7
2.0
1.8
1.5
1.1
1.0
0.8
0.7
0.0
CV death
HOPE
Nonfatal MI
EUROPA
PEACE
QUIET
HOPE Study Investigators. N Engl J Med. 2000;342:145-53.
EUROPA Investigators. Lancet. 2003;362:782-8.
PEACE Trial Investigators. N Engl J Med. 2004;351:2058-68.
Pitt B et al. Am J Cardiol. 2001;87:1058-63.
EUROPA, HOPE: Consistent benefit
of ACEI on CV outcomes
Event rate (%)
ACEI
Placebo
14.0
17.8
8.0
9.9
CV mortality
6.1
3.5
8.1
4.1
Myocardial infarction
9.9
4.8
12.3
6.2
Stroke
3.4
1.6
4.9
1.7
0.8
1.3
0.1
0.2
Composite outcome
Cardiac arrest
VBWG
Favors
Favors
ACE inhibitor Placebo
HOPE
(ramipril 10 mg)
EUROPA
(perindopril 8 mg)
0.5
1.0
Hazard ratio
1.5
EUROPA Investigators. Lancet. 2003;362:782-8.
HOPE Study Investigators. N Engl J Med. 2000;342:145-53.
VBWG
Should all patients with stable CAD without
HF receive an ACEI? Interpreting evidence
• Totality of clinical trial evidence supports ACEI for treatment of
stable CAD patients with/without HF
• Benefits have been shown in patients at all levels of risk
• All ACEIs may not have comparable effects for all indications
• Consider evidence and guidelines in selection of an ACEI
and dose.
• Both ramipril and perindopril reduce risk of CV events in
stable CAD patients without HF
– Ramipril 10 mg has proven efficacy in CAD patients ≥55 yrs
– Perindopril 8 mg has proven efficacy in CAD patients ≥18 yrs
Pitt B. N Engl J Med. 2004;351:2115-7.
EUROPA Investigators. Lancet. 2003;362:782-8.
HOPE Study Investigators. N Engl J Med. 2000;342:145-53.
PEACE Trial Investigators. N Engl J Med. 2004;351:2058-68.
VBWG
Evidence-based medicine: Updated guide-lines
for ACEI in CAD patients without HF
“ACE inhibitors should be used as routine secondary prevention
for patients with known CAD, particularly in diabetics without
severe renal disease.” . . . R.J. Gibbons et al.
“The HOPE trial…confirms that the ACE inhibitor ramipril
reduced CV death, MI, and stroke in patients who were at
high risk for, or had, vascular disease in the absence of
heart failure.” . . . R.J. Gibbons et al.
EUROPA “showed that an ACE inhibitor can have a
vasculoprotective effect in patients at lower risk than those
enrolled in the HOPE study.” . . . V. Snow et al.
Gibbons RJ et al. 2002 ACC/AHA Practice Guidelines. www.acc.org; July 2005.
Snow V et al. Ann Intern Med. 2004;141:562-7.
ACP guidelines for ACEI in chronic stable
angina or asymptomatic CAD
VBWG
• Symptomatic patients with chronic stable angina
(Level of evidence: A)
• Asymptomatic patients
– CAD with systolic dysfunction (Level of evidence: A)
– Diabetes with CAD (Level of evidence: A)
– Diabetes without CAD (Level of evidence: B)
Snow V et al. Ann Intern Med. 2004;141:562-7.
PERSUADE: PERindorpil SUbstudy of
coronary Artery disease and DiabEtes:
The diabetic substudy of EUROPA
Objective:
VBWG
Investigate the effect of long-term treatment with
perindopril added to standard therapy on CV
events in diabetic patients with CAD and without
heart failure
Population: N = 1502 with known diabetes
at randomization
Treatment:
Perindopril 8 mg (n = 721) or placebo (n = 781)
Follow-up:
4.2 years
Daly CA et al. Eur Heart J. 2005;26:1369-78.
VBWG
PERSUADE: Primary outcome
CV death, MI, cardiac arrest
20
RRR: 19%
95% CI: –7% to 38%
P = 0.13
16
Placebo
Perindopril
8 mg
Cumulative 12
frequency
(%)
8
4
0
0
1
2
3
4
5
Years from randomization
Daly CA et al. Eur Heart J. 2005;26:1369-78.
VBWG
PERSUADE and EUROPA: Comparable outcomes
Perindopril Placebo
EUROPA n = 6110 n = 6108
PERSUADE n = 721
n = 781
RRR (%)
CV mortality, nonfatal MI,
cardiac arrest
488
91
603
121
20
19
Total mortality
375
73
420
93
11
15
CV mortality
215
47
249
60
14
16
Fatal and nonfatal MI
320
56
418
78
24
23
Non–Q-wave infarction
212
37
273
60
23
34
Stroke
98
18
102
23
4
15
Heart failure
63
13
103
26
39
46

Favors
perindopril
0.5
1.0
EUROPA
Favors
placebo
2.0
PERSUADE
Daly CA et al. Eur Heart J. 2005;26:1369-78.
VBWG
PERSUADE and MICRO-HOPE:
Consistency of benefit
Favors ACEI
Favors placebo
Primary outcome
Total mortality
MICRO-HOPE
(N = 3577)
CV mortality
PERSUADE
(N = 1502)
All MI
Stroke
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
Relative risk (95% CI)
Daly CA et al. Eur Heart J. 2005;26:1369-78.
HOPE Study Investigators. Lancet. 2000;355:253-9.
PERSUADE: Clinical implications
VBWG
• Perindopril 8 mg once daily reduced CV events in patients
with CAD and diabetes
• Relative risk reduction in primary and secondary outcomes
with perindopril was similar to EUROPA
• Results extend the benefit of ACEI shown in MICRO-HOPE
to a lower-risk population with diabetes and CAD
Daly CA et al. Eur Heart J. 2005;26:1369-78.
VBWG
Are all ACEIs the same? Survival
1-year post-MI by ACEI at discharge
N = 7512, Canadian pharmacy database
100
90
Unadjusted
cumulative
survival
(%)
Ramipril
Perindopril n = 243
80
0
Reference = ramipril
n = 905
Lisinopril
n = 2201
Enalapril
n = 2577
Quinapril
n = 276
Fosinopril
n = 889
Captopril
n = 421
2
4
P < 0.001 log-rank
6
Months
8
10
12
Pilote L et al. Ann Intern Med. 2004;141:102-12.
VBWG
Multiple mechanisms of ACEI
in atherosclerotic CVD
Blood pressure lowering
Cardioprotective effects
Vasculoprotective effects
• Direct antiatherogenic
•  Preload and afterload
• Enhance endogenous fibrinolysis
•  LV mass
• Inhibit platelet aggregation
•  Sympathetic stimulation
• Antimigratory for mononuclear cells
•  Reperfusion injury
•  Matrix formation
• Improved myocardial remodeling
• Improve endothelial function
Metabolic syndrome
• Antioxidant
• Lipid neutral
• Anti-inflammatory
• Improved glucose metabolism
• Protection from plaque rupture
• Improved arterial compliance and tone
Lonn E et al. Eur Heart J. 2003;5(suppl):A43-8.
Clinical trials of ARBs: CV outcomes
Trial (year)
Patients
(Follow-up)
Treatment
BP
VBWG
CV outcomes
LIFE (2002)
Essential HTN
N = 9193
(4.8 years)
Losartan vs
atenolol
Similar 
VALUE (2004)
Essential HTN,
high CV risk
N = 15,245
(4.3 years)
Valsartan vs
amlodipine
Primary outcome similar
Greater  with
at study end
amlodipine
(2.0/1.6 mm Hg) Trend favors amlodipine
at 3 and 6 months
Difficult to interpret due
to BP difference
HTN = hypertension
13%  in primary outcome
(CV death, MI, stroke) with
ARB (P = 0.021) driven by
25%  in stroke (P = 0.001)
No difference in CV death/MI
Dahlöf B et al. Lancet. 2002;359:995-1003.
Julius S et al. Lancet. 2004;363:2022-31.
VBWG
LIFE: Effects of ARB vs -blockade
on primary outcome and components
N = 9193 with hypertension and ECG-LVH
Primary composite endpoint
(CV death/MI/stroke)
Primary outcome
components
(Losartan vs atenolol)
16
12
Proportion
of patients
with first
event (%)
10
Adjusted RR 13.0%
P = 0.021
(losartan vs atenolol)
Risk
increase
(%)
5
0
Losartan
4
0
18
30
Stroke
5
10
Risk
reduction 15
(%)
20
0 6
CV death
P = 0.491
Atenolol
8
MI
42
54
66
P = 0.206
25
P = 0.001
Time (months)
LIFE = Losartan Intervention for Endpoint Reduction
in Hypertension
Dahlöf B et al. Lancet. 2002;359:995-1003.
VALUE: Similar treatment effects
on primary outcome at study end
VBWG
14
Valsartan-based regimen
12
10
Proportion
of patients
with first
event (%)
8
6
Amlodipine-based regimen
4
2
HR = 1.03; 95% CI 0.94–1.14; P = 0.49
0
0
6
12 18 24 30 36 42 48 54 60 66
Time (months)
Julius S et al. Lancet. 2004;363:2049-51
VBWG
VALUE: SBP and outcome differences
during consecutive time periods
Primary outcome
Time
interval
(mos)
All study
0–3
3–6
6–12
12–24
24–36
36–48
Study end
∆ SBP
(mm Hg)
Favors
valsartan
Myocardial infarction
Favors
amlodipine
Favors
valsartan
Favors
amlodipine
2.2
3.8
2.3
2.0
1.8
1.6
1.4
1.7
0.5
1.0
2.0
Odds ratio
VALUE = Valsartan Antihypertensive
Long-Term Use Evaluation
4.0
0.5
1.0
2.0
4.0
Odds ratio
Julius S et al. Lancet. 2004;363:2022-31.
VBWG
Evidence of benefit: ACEI vs ARB
ACE
inhibitor
ARB
Heart failure
√
√
Post-MI
√
High CAD risk
√
Diabetes
√
√
Chronic kidney disease
√
√
Recurrent stroke prevention
√
High risk condition
Evidence from clinical trials supports the use of ACEIs
vs ARBs in a broader range of high-risk conditions
JNC 7. JAMA. 2003;289:2560-72.