HOPE: Heart Outcomes Prevention Evaluation study
Purpose
To evaluate whether the long-acting ACE inhibitor ramipril and/or vitamin E reduce the incidence of cardiovascular morbidity and mortality in a high-risk population
References
The HOPE Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000;342:145–53.
The HOPE Study Investigators. Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med 2000;342:154–60.
HOPE: Heart Outcomes Prevention Evaluation study - TRIAL DESIGN -
Treatment
Multicenter, multinational, randomized, double-blind, placebo-controlled parallel-group, two-by-two factorial study
Patients
55 years or older with history of vascular disease or diabetes mellitus, plus one other cardiovascular risk factor; patients with stroke or MI in previous month, heart failure or evidence of low ejection fraction excluded
Follow up and primary endpoint
Mean 5.0 years follow up for ramipril (4.5 for vitamin E). Primary endpoint composite of MI, stroke or cardiovascular death
HOPE: Heart Outcomes Prevention Evaluation study - TRIAL DESIGN continued -
Pre-randomization therapy
Ramipril 2.5 mg once daily (7–10 days), then placebo (10–14 days). Patients with side effects, abnormal serum creatinine/potassium, or noncompliance subsequently excluded
Treatment
9297 patients (2480 women, 6817 men) randomly assigned to receive one of four treatments for 5 years:
Ramipril 2.5 mg for 1 week, 5 mg for 3 weeks, then 10 mg + vitamin E 400 IU daily
Ramipril 2.5 mg for 1 week, 5 mg for 3 weeks, then 10 mg + placebo matching vitamin E treatment
Placebo matching ramipril treatment + vitamin E 400 IU daily
Placebo matching ramipril treatment + placebo matching vitamin E treatment
HOPE: Heart Outcomes Prevention Evaluation study - RESULTS -
Ramipril vs. placebo
Study halted 6 months early on recommendation of monitoring board because of consistent benefit of ramipril:
Composite primary endpoint of MI, stroke or death from cardiovascular causes significantly lower in ramipril group (14.0 vs. 17.8%, relative risk 0.78, P<0.001)
Individual primary endpoints (MI, stroke, death from cardiovascular causes), all-cause mortality, and secondary outcomes of revascularization and complications related to diabetes, significantly lower in ramipril group
New diagnosis of diabetes significantly lower in ramipril group (3.6 vs. 5.4%, relative risk 0.66, P<0.001)
Drug well tolerated as defined by permanent discontinuation of treatment (28.9% of ramipril group versus 27.3% placebo)
HOPE: Heart Outcomes Prevention Evaluation study - RESULTS continued -
Vitamin E vs. placebo
No benefit shown for vitamin E vs. placebo:
No significant difference in composite primary endpoint of MI, stroke or cardiovascular death in ramipril group (16.0 vs. 15.5%, relative risk 1.05, P=0.33)
No significant difference in individual primary endpoints or secondary cardiovascular outcomes or death from any cause
No significant adverse effects of vitamin E
HOPE: Heart Outcomes Prevention Evaluation study - RESULTS continued -
MI, stroke or death from cardiovascular causes
Days of follow up
P <0.001
0
0.00
500
1000
1500
0.05
0.10
0.15
0.20
The Hope Study Investigators.
N Engl J Med
2000;
342
:145
–
53.
Proportion
of patients
Placebo
Ramipril
HOPE: Heart Outcomes Prevention Evaluation study - RESULTS continued -
P
Primary outcome and deaths from any cause
The Hope Study Investigators.
N Engl J Med
2000;
342
:145
–
53.
Relative risk
(95% CI)
MI, stroke, or death from
cardiovascular causes
Death from cardiovascular causes
MI
Stroke
Death from noncardiovascular causes
Death from any cause
0.78 (0.70
–
0.86)
0.74 (0.64
–
0.87)
0.80 (0.70
–
0.90)
0.68 (0.56
–
0.84)
1.03 (0.85
–
1.26)
0.84 (0.75
–
0.95)
<0.001
<0.001
<0.001
<0.001
0.74
0.005
HOPE: Heart Outcomes Prevention Evaluation study - RESULTS continued -
P
Secondary outcomes and new diagnosis of diabetes
Relative
risk
Secondary outcomes
Revascularization
Hospitalization for unstable angina
Complications related to diabetes
Hospitalization for heart failure
New diagnosis of diabetes
0.85 (0.77–0.94)
0.98 (0.87–1.10)
0.84 (0.72–0.98)
0.88 (0.70–1.10)
0.66 (0.51–0.85)
0.002
0.68
0.03
0.25
<0.001
The Hope Study Investigators.
N Engl J Med
2000;
342
:145
–
53.
HOPE: Heart Outcomes Prevention Evaluation study - SUMMARY -
In high-risk patients not known to have low ejection fraction or heart failure:
Ramipril
Reduced rates of death, MI, stroke and revascularization
Reduced rates of new diagnosis of diabetes and complications due to diabetes
Vitamin E
Had no effect on outcomes