European trial on reduction of cardiac events with perindopril in stable coronary artery disease - EUROPA

Description:

The goal of the EUROPA trial was to evaluate the effect of treatment with the angiotensin-converting enzyme (ACE) inhibitor perindopril compared with placebo on cardiovascular (CV) events in patients with stable coronary artery disease (CAD).

Hypothesis:

In low-risk stable CAD patients, treatment with the ACE inhibitor perindopril will reduce CV events.

Study Design

Study Design:

Patients Screened: 13,655
Patients Enrolled: 12,218
Mean Follow Up: mean 3.7 years
Mean Patient Age: mean age 60 years
Female: 15%

Patient Populations:

Age >18 years; documented CAD (prior MI >3 months, PCI/CABG >6 months, stenosis on angiography ≥70%, males with chest pain and positive ETT or stress test); no scheduled revascularization; and no clinical signs of HF

Primary Endpoints:

Composite of CV mortality, nonfatal MI, and cardiac arrest

Secondary Endpoints:

Composite of total death, nonfatal MI, and cardiac arrest; HF; revascularization (percutaneous coronary intervention [PCI]/coronary artery bypass graft [CABG]); and stroke

Drug/Procedures Used:

Following a four-week, open-label run-in phase, patients were randomized to perindopril (8 mg/day, n=6,110) or placebo (n=6,108). The trial was conducted in 424 European countries.

Concomitant Medications:

Platelet inhibitors were used in 92% of patients; beta-blockers in 62%; and lipid-lowering therapy in 57%.

Principal Findings:

Baseline characteristics were well matched between the perindopril and control arms: prior myocardial infarction (MI) 65%, history of revascularization 55%, hypertension 27%, and history of stroke 3% in each arm. At three years, 80% of patients remained on treatment. Systolic blood pressure decreased 5 mm Hg, and diastolic blood pressure decreased 2 mm Hg in the perindopril arm.

The primary composite endpoint of CV mortality, nonfatal MI, and cardiac arrest was lower in the perindopril arm versus control (8.0% vs. 9.9%, RRR 20%, p=0.0003). Among the components of the composite endpoint, CV death and cardiac arrest were not significantly reduced (RRR 14% and RRR 46%, respectively), but nonfatal MI was significantly lower (RRR 22%).

The secondary composite endpoint of total mortality, nonfatal MI, unstable angina, and cardiac arrest was significantly lower in the perindopril arm (RRR 14%, p=0.0009), as was the composite of CV death/MI (RRR 19%), fatal and nonfatal MI (RRR 24%, p<0.001), and heart failure (HF) (RRR 39%, p=0.002), although the HF endpoint rate was relatively low (<2%).

Interpretation:

Among patients with stable CAD, treatment with the ACE inhibitor perindopril was associated with a reduction in the primary endpoint of CV mortality, nonfatal MI, and cardiac arrest compared with placebo.

Previous trials have demonstrated that ACE inhibitors are effective in other patient populations, including HF, left ventricular dysfunction, and high-risk CAD patients. However, the present trial is the largest to show such a benefit in stable, low-risk CAD patients.

As expected, the HF endpoint was also lower in the perindopril arm, a benefit which was observed early during the follow-up. The benefit in the primary endpoint was not observed until later during the follow-up course, at approximately two years.

References:

Presented by K.M. Fox at the European Society of Cardiology Congress, Vienna, Austria, September 2003.

The European trial on reduction of cardiac events with perindopril in stable coronary artery disease investigators. 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;362:782-8.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Statins, Acute Heart Failure, Hypertension

Keywords: Perindopril, Stroke, Myocardial Infarction, Follow-Up Studies, Constriction, Pathologic, Heart Arrest, Heart Failure, Ventricular Dysfunction, Left, Hypertension, Exercise Test


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