Evidence Based Snapshots

The Journal of Informed Pharmacotherapy 2002;9:152.

Effect of an ACE-inhibitor, Ramipril, on Death from Cardiovascular Causes, MI and Stroke in High Risk Patients (HOPE trial)

Reviewer: James McCormack, B.Sc. (Pharm), Pharm. D.
Reviewer's email address:
Reviewer's profession/specialty:
Professor, Faculty of Pharmaceutical Sciences, UBC

Original Citation

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 PubMed citation

Overall Study Question

These investigators evaluated the benefit of treating high risk patients with either ramipril or placebo.


9,297 patients mean age 66 (26% women) with a history of CAD (80%), stroke (11%), peripheral vascular disease (45%), or diabetes (39%) PLUS AT LEAST ONE OF either hypertension (47%), elevated total cholesterol (66%), low HDL (19%), smoker (14%), or documented microalbuminuria (21%) - excluded if they had heart failure - prior to randomization - run in phase - 2-3 weeks - 1035 of 10,576 dropped out due to noncompliance, side effects, abnormal serum creatinine/ potassium or withdrawal of consent.


Ramipril 10 mg PO daily (starting at 2.5mg) or placebo.


5 years 


MI, stroke, death from CHD (%) All deaths (%) MI (%) Revascularization (%) CHF (%) Strokes (%)
Ramipril 14.0 10.4 9.9 16.0 9.0 3.4
Placebo 17.8 12.2 12.3 18.3 11.5 4.9
Relative Risk Reduction 21 15 20 13 22 31
Absolute Risk Reduction 3.8 1.8 2.4 2.3 2.5 1.5
NNT/NNH over 5 years 28 56 43 38 40 67

NNT = numbers needed to treat, NNH = numbers needed to harm

Blood pressure was 3/2 mmHg (2 years) to 2/1 mmHg different at end of trial.

How does this study contribute to the use of ACE inhibitors in high-risk patients?

This study shows that treatment of patients with a history of a cardiovascular complication or diabetes plus at least one other risk factor with ramipril reduces the chance of MI, stroke, death from CHD by 3.8%.  Whether this benefit is unique to ACE inhibitors versus other antihypertensives or antihyperlipidemics is not clearly known.

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