Efficacy of Perindopril in Reduction of Cardiovascular Events Among Patients With Stable Coronary Artery Disease: Randomised, Double-Blind, Placebo-Controlled, Multicentre Trial (The EUROPA Study)

Lancet. 2003 Sep 6;362(9386):782-8. doi: 10.1016/s0140-6736(03)14286-9.

Abstract

Background: Treatment with angiotensin-converting-enzyme (ACE) inhibitors reduces the rate of cardiovascular events among patients with left-ventricular dysfunction and those at high risk of such events. We assessed whether the ACE inhibitor perindopril reduced cardiovascular risk in a low-risk population with stable coronary heart disease and no apparent heart failure.

Methods: We recruited patients from October, 1997, to June, 2000. 13655 patients were registered with previous myocardial infarction (64%), angiographic evidence of coronary artery disease (61%), coronary revascularisation (55%), or a positive stress test only (5%). After a run-in period of 4 weeks, in which all patients received perindopril, 12218 patients were randomly assigned perindopril 8 mg once daily (n=6110), or matching placebo (n=6108). The mean follow-up was 4.2 years, and the primary endpoint was cardiovascular death, myocardial infarction, or cardiac arrest. Analysis was by intention to treat.

Findings: Mean age of patients was 60 years (SD 9), 85% were male, 92% were taking platelet inhibitors, 62% beta blockers, and 58% lipid-lowering therapy. 603 (10%) placebo and 488 (8%) perindopril patients experienced the primary endpoint, which yields a 20% relative risk reduction (95% CI 9-29, p=0.0003) with perindopril. These benefits were consistent in all predefined subgroups and secondary endpoints. Perindopril was well tolerated.

Interpretation: Among patients with stable coronary heart disease without apparent heart failure, perindopril can significantly improve outcome. About 50 patients need to be treated for a period of 4 years to prevent one major cardiovascular event. Treatment with perindopril, on top of other preventive medications, should be considered in all patients with coronary heart disease.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / prevention & control*
  • Cause of Death
  • Coronary Disease / drug therapy*
  • Coronary Disease / mortality
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Heart Arrest / prevention & control
  • Heart Failure / prevention & control
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / prevention & control
  • Perindopril / therapeutic use*
  • Treatment Outcome

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Perindopril