EUROPA study (efficacy of perindopril in reduction of cardiovascular (CV) events among patients with stable coronary artery disease)

• Evidence from trials such as AIRE and SAVE have shown that reatment 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. The EUROPA investigators designed a trial that assessed whether the ACE inhibitor perindopril reduced cardiovascular risk in a low-risk population with stable coronary heart disease and no apparent heart failure

Study Design and Method

• patients were recruited 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)
• 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

Results

• 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 during the study

Conclusions

• among patients with stable coronary heart disease without apparent heart failure, the evidence from the EUROPA study has shown that perindopril can significantly improve outcome
• about 50 patients need to be treated for a period of 4 years to prevent one major cardiovascular event
• 'these results provide strong support for considering this ACE inhibitor perindopril, in addition to other preventive treatments, irrespective of cardiac function or risk factors for all patients with coronary heart disease (1)'

Reference:

1. Lancet. 2003 Sep 6;362(9386):782-8.