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Evevident
Original paper
2000NEJMCardiology

HOPE

Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients

RCTCardiovascular prevention

On this page

Overview

Ramipril reduced major cardiovascular events in high-risk patients without heart failure.

Clinical takeaway

HOPE broadened ACE inhibitor use from blood-pressure and heart-failure treatment to vascular protection in high-risk patients, especially those with diabetes or established vascular disease.

Key result

CV death, MI, or stroke occurred in 14.0% with ramipril vs 17.8% with placebo.

Practice impact

ACE inhibitors became core risk-reduction therapy for selected high-risk vascular patients.

Evidence

Study design

Randomized, double-blind, placebo-controlled trial.

Enrollment

9,297

Follow-up

Mean 5 years.

Geography

Multinational

Clinical question

Does ramipril reduce cardiovascular events in high-risk patients without known low ejection fraction or heart failure?

Population

  • Patients at least 55 years old with vascular disease or diabetes plus another cardiovascular risk factor.
  • Patients without known low ejection fraction or heart failure.

Intervention

Ramipril 10 mg daily.

Comparator

Placebo.

Primary outcome

Composite of myocardial infarction, stroke, or cardiovascular death.

Ramipril reduced major cardiovascular events in high-risk patients without heart failure.

Relative risk / 0.78 / CI 95% CI 0.70-0.86 / p=<0.001

Key results

  • Primary composite outcome: 14.0% with ramipril vs 17.8% with placebo; RR 0.78.
  • Cardiovascular death, MI, and stroke were each significantly reduced.
  • Benefits exceeded what would be expected from the modest blood-pressure difference alone.

Harms

  • Cough was more common with ramipril.
  • Hypotension and renal-function changes remain practical monitoring issues with ACE inhibitors.

Clinical Use

When to cite

  • When adding ACE inhibitor therapy for high-risk vascular disease beyond simple BP control.

Practice impact

  • Supported ACE inhibitor therapy for vascular protection in high-risk patients, including many with diabetes or established atherosclerotic disease.

Applicability

  • Best applied to patients resembling HOPE participants: older adults with vascular disease or diabetes plus additional risk.

Limitations

  • Background statin and revascularization use differ from contemporary care.
  • Not a trial of low-risk primary prevention.

Common misinterpretations

  • Do not generalize HOPE to all patients with uncomplicated hypertension; ALLHAT and other BP trials answer first-line antihypertensive questions.

Related evidence

ALLHAT - ContextSPRINT - Context

Citation

Heart Outcomes Prevention Evaluation Study Investigators, Yusuf S, Sleight P, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342(3):145-153. doi:10.1056/NEJM200001203420301

Ramipril significantly reduces the rates of death, myocardial infarction, and stroke in a broad range of high-risk patients.