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The Heart Outcomes Prevention Evaluation Study - HOPE - Ramipril
Description:
The goal of the trial was to evaluate ramipril and vitamin E for prevention of myocardial infarction (MI), stroke, or cardiovascular (CV) death in patients at high risk for CV events, but without left ventricular dysfunction or heart failure.
Hypothesis:
Ramipril, an angiotensin-converting enzyme (ACE) inhibitor, and vitamin E, a naturally occurring antioxidant vitamin, will be associated with a reduction in the risk of MI, stroke, or CV death in an at-risk population.
Study Design
Patients Enrolled: 9,297
Mean Follow Up: Mean follow-up 4.5 years
Mean Patient Age: Mean age 66 years
Female: 27
Mean Ejection Fraction: >40%
Patient Populations:
Age ≥55 years, and history of coronary artery disease, stroke, peripheral vascular disease, or diabetes plus at least one other CV risk factor (hypertension, elevated total cholesterol levels, low high-density lipoprotein cholesterol levels, cigarette smoking, or documented microalbuminuria)
Exclusions:
Heart failure, known low ejection fraction (<40%), use of an ACE inhibitor or vitamin E, uncontrolled hypertension or overt nephropathy, or MI or stroke within four weeks prior to enrollment
Primary Endpoints:
Combined endpoint of MI, stroke, or CV death
Secondary Endpoints:
Death from any cause, need for revascularization; hospitalization for unstable angina, or heart failure; and complications related to diabetes (whether or not hospitalization was required)
Drug/Procedures Used:
Patients were randomized to ramipril (10 mg/day, n=4,645) or placebo (n=4,652). In a factorial design, patients were also randomized to vitamin E (n=4,761) or placebo (n=4,780).
Principal Findings:
Baseline characteristics were well balanced between the treatment groups, with 52% having a prior MI, 55% stable angina, 25% unstable angina, 43% peripheral vascular disease, and 39% diabetes. Permanent discontinuation of study medication was reported in 28.9% of the ramipril group and 27.3% of the placebo group. Discontinuation due to cough was more frequent in the ramipril group than placebo (7.3% vs. 1.8%). Mean blood pressure was 139/79 mm Hg in both groups at baseline and was reduced to 136/78 mm Hg in the ramipril group and 139/77 mm Hg in the placebo group at study end.
The primary endpoint of CV death, MI, or stroke occurred less frequently in the ramipril group than the placebo group (14.0% vs. 17.8%, relative risk [RR] 0.78, p<0.001). Each of the individual components of the composite endpoint also occurred less frequently in the ramipril group: CV death (6.1% vs. 8.1%, RR 0.74, p<0.001); MI (9.9% vs. 12.3%, RR 0.80, p<0.001); and stroke (3.4% vs. 4.9%, RR 0.68, p<0.001).
Total mortality was less frequent in the ramipril group (10.4% vs. 12.2%, RR 0.84, p=0.005). The rate of revascularization was lower in the ramipril group (16.0% vs. 18.3%, RR 0.85, p=0.002), as was complications related to diabetes (6.4% vs. 7.6%, RR 0.84, p=0.03), but there was no difference in the other secondary endpoints of hospitalization for unstable angina (11.9% vs. 12.1%, RR 0.98, p=0.68) or hospitalization for heart failure (3.0% vs. 3.4%, RR 0.88, p=0.25).
Interpretation:
Among patients at high-risk for CV events but without left ventricular dysfunction or heart failure, treatment with the ACE inhibitor ramipril was associated with a reduction in the primary endpoint of CV death, MI, or stroke, as well as each of the individual endpoints, compared with placebo.
ACE inhibitor therapy had initially been targeted toward treatment of heart failure, where it was associated with a reduction in MI in patients with low ejection fraction. It was also studied in patients with acute MI. These findings led to the hypothesis that ACE inhibitors might also be effective in the prevention of CV events in high-risk patients without left ventricular dysfunction.
References:
Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:145-53.
Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:154-60.
The HOPE (Heart Outcomes Prevention Evaluation) Study: the design of a large, simple randomized trial of an angiotensin-converting enzyme inhibitor (ramipril) and vitamin E in patients at high risk of cardiovascular events. The HOPE study investigators. Can J Cardiol 1996;12:127-37.
Keywords: Myocardial Infarction, Stroke, Risk Factors, Ramipril, Peripheral Vascular Diseases, Smoking, Vitamins, Cholesterol, alpha-Tocopherol, Cough, Lipoproteins, HDL, Hypertension, Diabetes Mellitus
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