Role of RAAS Modulation: Recent Clinical Trials CAD Diabetes ACEIs and ARBs VBWG.
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Transcript of Role of RAAS Modulation: Recent Clinical Trials CAD Diabetes ACEIs and ARBs VBWG.
Role of RAAS Modulation:Recent Clinical Trials
• CAD• Diabetes • ACEIs and ARBs
VBWG
Benefit of ACE inhibition in CADBenefit of ACE inhibition in CAD
EUROPA
HOPE
All CAD patientsAll CAD patients
Post-MI, HF, LVEF <40%
SOLVDSAVEAIRETRACE
SOLVD(prev)
High risk
Bertrand ME. Curr Med Res Opin. 2004;20:1559-69.
VBWG
EUROPA: EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease
EUROPA Investigators. Lancet. 2003;362:782-8.
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
VBWG
EUROPA: Baseline characteristics
EUROPA Investigators. Lancet. 2003;362:782-8.
Female
History of CAD
– MI
– PCI
– CABG
Documented CAD
– Angiographic evidence (stenosis >70% )
14.5
100
64.9
29.0
29.3
60.4
14.7
100
64.7
29.5
29.4
60.5
– Positive stress test
(in men w/chest pain)
History of stroke/TIA
PVD
Hypertension
Diabetes
Hypercholesterolemia
22.6
3.4
7.1
27.0
11.8
63.3
23.3
3.3
7.4
27.2
12.8
63.3
Placebo (%)(n = 6108)
Perindopril (%)
(n = 6110)
VBWG
EUROPA: Concomitant medications
Platelet inhibitors
Beta-blockers
Lipid-lowering agents
Nitrates
Calcium channel blockers
Diuretics
92
62
58
43
32
9
91
63
69
NA
NA
NA
EUROPA Investigators. Lancet. 2003;362:782-8.
Baseline (%) 3 Years (%)*
*Concomitant medications recorded in 11,547 patients
VBWG
EUROPA Investigators. Lancet. 2003;362:782-8.Fox KM. Br J Cardiol. 2004;11:195-204.
EUROPA: Primary outcome
12
4
10
0
1 3 4
14
0
Placebo
Perindopril 8 mg8
6
2
52
Primary outcome
(%)
Time (years)
10%
11%
14%
20%
CV death, MI, cardiac arrest
RRR 20% (95% CI: 9%–29%)AR 8.0% vs 9.9%
P = 0.0003
P < 0.05
P = 0.35
AR = absolute risk (perindopril vs placebo)
VBWG
RRR 24%AR 5.2% vs 6.8%
P < 0.001
EUROPA Investigators. Lancet. 2003;362:782–8.
Fatal and nonfatal MI
RRR 39%AR 1.0% vs 1.7%
P = 0.002
2
4
Events(%)
0
10
6
8
0 1 2 3 4 5
Years
Placebo
Perindopril8 mg
0.5
1.0
0.0
2.0
1.5
0 1 2 3 4 5
Years
Placebo
Perindopril8 mg
HF hospitalization
EUROPA: Effect of ACEI on fatal/nonfatal MI and HF hospitalizations
AR = absolute risk (perindopril vs placebo)
VBWG
EUROPA Investigators. Lancet. 2003;362:782-8.
8.0
14.8
7.9
6.1
3.5
5.2
CV mortality, MI, cardiac arrest
Total mortality, MI, UA, cardiac arrest
CV mortality, MI
Total mortality
CV mortality
Fatal/nonfatal MI
Favorsperindopril
Favorsplacebo
Perindopril (%)(n = 6110)
Placebo (%)(n = 6108)
9.9
17.1
9.8
6.9
4.1
6.8
0.5 1.0 2.0
EUROPA: Benefit of ACEI on primary and secondary outcomesN = 12,218
VBWG
EUROPA Investigators. Lancet. 2003;362:782-8.
5.6
0.1
1.6
9.4
1.0
Unstable angina
Cardiac arrest
Stroke
Revascularization
HF w/hospital admission
Favorsperindopril
Favorsplacebo
Perindopril (%)(n = 6110)
Placebo (%)(n = 6108)
6.0
0.2
1.7
9.8
1.7
0.5 1.0 2.0
EUROPA: Benefit of ACEI on selected secondary outcomesN = 12,218
VBWG
EUROPA: Consistent benefits in predefined subgroups
EUROPA Investigators. Lancet. 2003;362:782-8.
Male
Female
≤55
56–65
≥66
Perindopril(n = 6110)
Placebo(n = 6108)
0.5 1.0 2.0
n
10,439
1779
3948
4439
3831
8.2
6.9
6.5
6.9
10.7
10.1
8.8
8.9
8.1
12.9
Primary events (%)
Favorsperindopril
Favorsplacebo
Age (years)
N = 12,218
VBWG
EUROPA: Consistent benefits in predefined subgroups (continued)
EUROPA Investigators. Lancet. 2003;362:782-8.
Previous MI
No previous MI
Previous revascularization
No previous revascularization
Hypertension
No hypertension
Diabetes mellitus
No diabetes mellitus
Perindopril(n = 6110)
Placebo(n = 6108)
0.5 1.0 2.0
n
7910
4299
6709
5509
3312
8906
1502
10,716
8.9
6.4
6.6
9.6
9.8
7.3
12.6
7.4
11.3
7.3
8.0
12.2
12.0
9.1
15.5
9.0
Primary events (%)
Favorsperindopril
Favorsplacebo
VBWG
EUROPA: Benefit of perindopril was on top of recommended medications
EUROPA Investigators. Lancet. 2003;362:782-8.
7.0
9.3
7.6
8.7
9.9
7.1
0.5 1.0 2.0
8.3
11.9
10.2
9.4
11.7
9.0
Lipid-lowering drug
No lipid-lowering drug
-blockers
No -blockers
Calcium channel blockers
No calcium channel blockers
Favorsperindopril
Favorsplacebo Perindopril
(n = 6110) Placebo
(n = 6108)
Primary events (%)
VBWG
EUROPA: Risk reduction with perindopril EUROPA: Risk reduction with perindopril stratified by baseline systolic BP levelstratified by baseline systolic BP level
<120 120 to <140 140
Primaryendpoint
relative riskreduction withperindopril (%)
Remme WJ. Circulation. 2004;110(suppl):III-628.
Baseline SBP (mm Hg)
39
17 18
40
35
30
25
20
15
10
5
0
N = 12,218
No interaction between treatment and SBP:
P = 0.464
VBWG
EUROPA: Systolic BP reduction during run-in did not affect risk reduction during trial
RRR 20%RRR 20% RRR 18%RRR 18%
SBP decreaseduring run-in
No SBP decreaseduring run-in
0
2
4
6
8
10
12
n = 4263n = 4263
n = 4303n = 4303
n = 1841n = 1841
n = 1804n = 1804
Primaryevent(%)
PerindoprilPlacebo
Run in = 4 weeks when all patients receivedperindopril 8 mg
N = 12,218
Remme WJ. Circulation. 2004;110(suppl):III-628.
VBWG
EUROPA vs HOPE: Inclusion criteria
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)
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)
EUROPA Investigators. Lancet. 2003;362:782-8.HOPE Study Investigators. N Engl J Med. 2000;342:145-53.
HOPE patients were at higher risk than EUROPAHOPE patients were at higher risk than EUROPA
VBWG
EUROPA HOPE
Age, mean (yrs) 60 66
BP (mm Hg) 137/82 139/79
Known CAD (%) MI (%)
PVD (%)
Stroke/TIA (%)
Revascularization (%)
Diabetes (%)
Hypertension (%)
Hypercholesterolemia (%)
10065
7
3
58
12
27
63
8053
43
11
44
39
47
66
EUROPA Investigators. Lancet. 2003;362:782-8.HOPE Study Investigators. N Engl J Med. 2000;342:145-53.
EUROPA vs HOPE: Study populationsVBWG
EUROPA vs HOPE: Event rates in placebo groups reflect differences in baseline risk
80% higher annual rate of CV and total mortality in HOPE80% 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.
CV mortality Total mortality
Annualizedevent ratein placebo
groups(%)
HOPEEUROPA
1.8
2.7
1.0
1.5
0.0
0.5
1.0
1.5
2.0
2.5
3.0
VBWG
EUROPA vs HOPE: Treatment more intensive in EUROPA than in HOPE
EUROPA Investigators. Lancet. 2003;362:782-8.HOPE Study Investigators. N Engl J Med. 2000;342:145-53.*Mostly aspirin
0
20
40
60
80
100
Antiplateletdrugs*
Beta-blockers
Lipid-lowering
drugs
Baseline medication
%
75
92
39
62
28
57
HOPEEUROPA
VBWG
EUROPA: Clinical implications
• 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
EUROPA Investigators. Lancet. 2003;362:782-8.Remme WJ. Circulation. 2004;110(suppl):III-628.
Treatment with perindopril should be considered in all Treatment with perindopril should be considered in all CAD patients, including patients at low riskCAD patients, including patients at low risk
VBWG
PEACE: Prevention of Events with Angiotensin Converting Enzyme inhibition
PEACE Trial Investigators. N Engl J Med. 2004;351:2058-68.
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
Primaryoutcome: CV death, nonfatal MI, CABG, PCI
VBWG
PEACE Trial Investigators. N Engl J Med. 2004;351:2058-68.
PEACE: Primary outcome
Trandolapril4 mg
Placebo30
20
10
15
5
1 2 3 4 5
25
0
6
Patients(%)
Time (years)
CV death, MI, CABG/PCI; N = 8290
4% Risk reductionHR 0.96 (0.88–1.06)
P = 0.43
0
VBWG
EUROPA vs PEACE: Differences in compliance
EUROPA (perindopril 8 mg) PEACE (trandolapril 4 mg)
EUROPA Investigators. Lancet. 2003;362:782-8.PEACE Trial Investigators. N Engl J Med. 2004;351:2058-68.
0
20
40
60
80
100
On study ACEI
At targetACEI dose
Patients (%)
93
68.6
8174.5
3 Years
VBWG
ACEI trials in CAD without HF: Primary outcomes
HOPE Study Investigators. N Engl J Med. 2000;342:145-53.Pitt B et al. Am J Cardiol. 2001;87:1058-63.
PEACECV death/MI/CABG/PCI
HOPECV death/MI/stroke
15
5
10
0
20
0
Placebo
Ramipril 10 mg
Time (years)
%
2 41
22% Risk reductionHR 0.78 (0.70–0.86)
P < 0.001
3Time (years)
12
4
10
0
1 3 4
14
0
Placebo
Perindopril 8 mg
86
2
52
EUROPACV death/MI/cardiac arrest
20% Risk reductionHR 0.80 (0.71–0.91)
P = 0.0003
40
20
30
0
50
0
Placebo
Quinapril 20 mg
Time (years)1
4% Risk increaseHR 1.04 (0.89–1.22)
P = 0.6
10
2 3
QUIETAll CV events
Time (years)
Trandolapril4 mg
Placebo30
20
10
15
5
1 2 3 4 5
25
06
4% Risk reductionHR 0.96 (0.88–1.06)
P = 0.43
EUROPA Investigators. Lancet. 2003;362:782-8.PEACE Trial Investigators. N Engl J Med. 2004;351:2058-68.
%
%
%
VBWG
N 12,218 9297 8290 1750
Follow-up (yrs) 4.2 4.5 4.8 2.3
ACEI/dose (mg) P-8 R-10 T-4 Q-20
Age (yrs) 60 66 64 58
Men (%) 85 73 82 82
CAD/Cor rev (%) 100/55 80/44 100/72 100/100
Diabetes (%) 12 39 17 16
Hypertension (%) 27 47 46 47
Prior MI (%) 65 53 55 49
Ejection fraction (%) NA NA 58 59
PVD (%) 7 43 NA NA
ACEI trials in CAD patients without HF: Key baseline characteristics
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.
EUROPA HOPE PEACE QUIET
VBWG
EUROPA, HOPE, PEACE, QUIET: Totality of trial evidence
MI
Stroke
All-cause death
Event rate (%)
Favors ACEIACEI
Revascularization
Favors placeboPlacebo
7.5
6.4
2.1
15.5
8.9
7.7
2.7
16.3
0.86
0.86
0.77
0.93
0.0004
0.0004
0.0004
0.025
0.5 0.75 1.251Odds ratio
P
Pepine CJ, Probstfield JL. Vasc Bio Clin Pract. CME Monograph; UF College of Medicine. 2004;6(3).
VBWG
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
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.
*at 3 yrs†at study end
EUROPA, HOPE, PEACE, QUIET: CV therapies at entry/during study
VBWG
ACEI outcome trials in CAD patients without HF: BP at entry/during study
BP (mm Hg) 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
Difference in mean BP during follow-up (ACEI vs placebo)
5/2 3.3/1.2 3/1.2 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.
*Run-in BP maintained during study†at study end‡at 3 years
VBWG
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.
HOPE, EUROPA, PEACE, QUIET: Differences in baseline CV risk
HOPE EUROPA PEACE
Annualized event rate in placebo group
(%/yr)
CV death Nonfatal MI
QUIET
1.8
1.00.8 0.7
2.7
1.5
1.1
2.0
0.0
1.0
2.0
3.0
VBWG
EUROPA, HOPE: Consistent benefit of ACEI on CV outcomes
Event rate (%)
14.0 17.8
8.0 9.9
6.1 8.1
3.5 4.1
9.9 12.3
4.8 6.2
3.4 4.9 1.6 1.7
0.8 1.3
0.1 0.2
Composite outcome
CV mortality
Myocardial infarction
Stroke
Cardiac arrest
FavorsACE inhibitor
FavorsPlacebo
HOPE(ramipril 10 mg)
EUROPA(perindopril 8 mg)
EUROPA Investigators. Lancet. 2003;362:782-8.HOPE Study Investigators. N Engl J Med. 2000;342:145-53.
Hazard ratio 0.5 1.0 1.5
ACEI Placebo
VBWG
• 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.
Should all patients with stable CAD without HF receive an ACEI? Interpreting evidence
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 ofheart 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.
VBWG
ACP guidelines for ACEI in chronic stable angina or asymptomatic CAD
• 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.
VBWG
PERSUADE: PERindorpil SUbstudy of coronary Artery disease and DiabEtes: The diabetic substudy of EUROPA
Objective: 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
Cumulative frequency
(%)
Perindopril8 mg
Placebo
2 3 4 510
Years from randomization
0
4
8
12
16
20
RRR: 19%95% CI: –7% to 38%
P = 0.13
CV death, MI, cardiac arrest
Daly CA et al. Eur Heart J. 2005;26:1369-78.
VBWG
PERSUADE and EUROPA: Comparable outcomes
EUROPAPERSUADE Favors
perindoprilFavorsplacebo
Perindopril n = 6110
n = 721
Placebo n = 6108
n = 781
RRR (%)
PERSUADEEUROPA
CV mortality, nonfatal MI,cardiac arrest
488 603 2091 121 19
Total mortality375 420 11
73 93 15
CV mortality 215 249 1447 60 16
Fatal and nonfatal MI320 418 24
56 78 23
Non–Q-wave infarction 212 273 2337 60 34
Stroke 98 102 418 23 15
Heart failure13 26 4663 103 39
0.5 1.0 2.0
Daly CA et al. Eur Heart J. 2005;26:1369-78.
VBWG
PERSUADE and MICRO-HOPE: Consistency of benefit
Daly CA et al. Eur Heart J. 2005;26:1369-78.HOPE Study Investigators. Lancet. 2000;355:253-9.
Primary outcome
Total mortality
CV mortality
All MI
Stroke
0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8
Favors ACEI Favors placebo
Relative risk (95% CI)
MICRO-HOPE(N = 3577)
PERSUADE(N = 1502)
VBWG
PERSUADE: Clinical implications
• 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
Pilote L et al. Ann Intern Med. 2004;141:102-12.
N = 7512, Canadian pharmacy database
Reference = ramipril
Are all ACEIs the same? Survival 1-year post-MI by ACEI at discharge
P < 0.001 log-rank
100
90
80
121086420 Months
Captopril
Ramipril
Quinapril
Fosinopril
Lisinopril
Enalapril
Perindopril
Unadjusted cumulative
survival(%)
n = 421
n = 905
n = 276
n = 889
n = 2201
n = 2577
n = 243
VBWG
Multiple mechanisms of ACEI in atherosclerotic CVD
Lonn E et al. Eur Heart J. 2003;5(suppl):A43-8.
Blood pressure lowering
Cardioprotective effects
• Preload and afterload
• LV mass
• Sympathetic stimulation
• Reperfusion injury
• Improved myocardial remodeling
Vasculoprotective effects
• Direct antiatherogenic
• Enhance endogenous fibrinolysis
• Inhibit platelet aggregation
• Antimigratory for mononuclear cells
• Matrix formation
• Improve endothelial function
• Antioxidant
• Anti-inflammatory
• Protection from plaque rupture
• Improved arterial compliance and tone
Metabolic syndrome
• Lipid neutral
• Improved glucose metabolism
VBWG
Clinical trials of ARBs: CV outcomes
Similar
Greater with amlodipine (2.0/1.6 mm Hg)
Losartan vs atenolol
Valsartan vs amlodipine
Essential HTN
N = 9193
(4.8 years)
Essential HTN, high CV risk
N = 15,245
(4.3 years)
LIFE (2002)
VALUE (2004)
BPTreatment
Patients
(Follow-up)Trial (year)
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
CV outcomes
Primary outcome similar at study end
Trend favors amlodipine at 3 and 6 months
Difficult to interpret due to BP difference
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
Dahlöf B et al. Lancet. 2002;359:995-1003.
N = 9193 with hypertension and ECG-LVH
LIFE = Losartan Intervention for Endpoint Reduction in Hypertension
16
Proportionof patientswith first
event (%)
12
8
4
0
60 18 30 5442 66
AtenololLosartan
Primary composite endpoint(CV death/MI/stroke)
Adjusted RR 13.0%P = 0.021
(losartan vs atenolol)
Time (months)
5
10Risk
increase(%)
0
5
10
15
20
25
Primary outcome components
(Losartan vs atenolol)
Riskreduction
(%)
P = 0.206
CV death
P = 0.491
Stroke
MI
P = 0.001
VBWG
VALUE: Similar treatment effectson primary outcome at study end
14
4
2
0
Proportionof patientswith first
event (%)
0 12 3018 24 54 60 66
Time (months)
6
8
10
12
6 36 42 48
HR = 1.03; 95% CI 0.94–1.14; P = 0.49
Valsartan-based regimen
Amlodipine-based regimen
Julius S et al. Lancet. 2004;363:2049-51
VBWG
Timeinterval(mos)
∆ SBP(mm Hg)
Odds ratio Odds ratio
Favorsvalsartan
Favorsamlodipine
Favorsvalsartan
Favorsamlodipine
Primary outcome Myocardial infarction
0.5 1.0 2.0 4.0 0.5 1.0 2.0 4.0
All study 2.20–3 3.83–6 2.36–12 2.012–24 1.824–36 1.6
Study end 1.736–48 1.4
Julius S et al. Lancet. 2004;363:2022-31.
VALUE: SBP and outcome differencesduring consecutive time periods
VALUE = Valsartan Antihypertensive Long-Term Use Evaluation
VBWG
High risk condition ACE
inhibitor ARB
Heart failure √ √
Post-MI √
High CAD risk √
Diabetes √ √
Chronic kidney disease √ √
Recurrent stroke prevention √
JNC 7. JAMA. 2003;289:2560-72.
Evidence of benefit: ACEI vs ARB
Evidence from clinical trials supports the use of ACEIsvs ARBs in a broader range of high-risk conditions
VBWG