Photo for HOPE


Official Title

Heart Outcomes Prevention Evaluation




To evaluate the use of the ACE inhibitor ramipril and of vitamin E in high-risk patients with chronic stable vascular disease and/or diabetes and additional risk factor(s). The trial showed clear benefit for ramipril and a neutral effect for vitamin E. Considered a landmark trial sin CV prevention, HOPE led to regulatory approvals for a new indication for the study drug in 40 countries and had a major impact on guidelines and patterns of practice worldwide. The HOPE Extension trial consisted of passive follow-up for ramipril arm of the trial and continued blinded study drug administration and follow-up for the vitamin E of the trial for additional 2.6 years and showed maintained benefit for ramipril and neutral effect for vitamin E. HOPE included also a large number of substudies and additional analyses (carotid IMT, LV function, economic substudy, biomarkers, renal outcomes, heart failure, effects in people with diabetes, women, the elderly) and over 60 publications.

Study Design

Randomized, double-blind, controlled trial with a factorial design.

Primary Endpoint

The primary study outcome was the composite of CV death, myocardial infarction and stroke. Secondary outcomes were all-cause death, revascularizations, hospitalization for heart failure, hospitalization for unstable angina and complications related to diabetes. All primary and secondary outcomes were adjudicated (except revascularizations.)

Number of Patients


Number of Sites


Number of Countries


Study Period


Principal Investigator

Salim Yusuf

Program Manager

Not Applicable

Research Coordinator

Jackie Bosch

Key Publications

  • Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G; The Heart Outcomes Prevention Evaluation 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. – highest cited publication in clinical medicine in year 2000.
  • Yusuf S, Dagenais G, Poge J, Bosch J, Sleight P; The Heart Outcomes Prevention Evaluation Study Investigators. Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med 2000 Jan 20;342:154-60.
  • The HOPE Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet 2000;355:253-9.
  • Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JM, Ross C, Arnold A, Sleight P, Probstfield J, Dagenais GR; HOPE and HOPE-TOO Trial Investigators. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005;293:1338-47.
  • Bosch J, Lonn E, Pogue J, Arnold JM, Dagenais GR, Yusuf S; HOPE/HOPE-TOO Study Investigators. Long-term effects of ramipril on cardiovascular events and on diabetes: results of the HOPE study extension. Circulation 2005;112:1339-46.