Risk Assessment and Risk Reduction by Perindopril in Patients With Normal Left Ventricular Function or Previous Revascularization in the EUROPA Study
Willem J. Remme, Jaap W. Deckers, Dick Goedhart, Maarten L. Simoons, Kim M. Fox, Roberto Ferrari, Michel E. Bertrand, Sticares Cardiovascular Research Institute, Rhoon, The Netherlands
Risk Assessment and Reduction/Rehabilitation
Background: In the EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA), perindopril 8 mg daily significantly reduced cardiovascular (CV) death, non-fatal myocardial infarction (MI) and resuscitated cardiac arrest by 20%,compared to placebo, after a follow-up of 4.2 years in patients (pts) with stable coronary artery disease (CAD). Subsequent risk profiling showed a consistent risk reduction among high, intermediate and low risk pts. Whether this pertains in pts with a normal left ventricular (LV) function or previous revascularisation is unknown.
Methods: Of the 12218 pts included in EUROPA, 6878 had a quantified LV ejection fraction (LVEF) = 40% and 6709 a previous revascularization at baseline. A risk score (tertiles) was composed of the following independent risk factors identified by multivariate analysis: age >65 years, male gender, BMI>30kg/m2, symptomatic CAD, previous stroke or peripheral vascular disease, previous myocardial infarction, diabetes, smoking, high cholesterol, family history of CAD, systolic blood pressure >130 mmHg, creatinine clearance = 80ml/min.
Results: In pts with LVEF= 40% the rates of CV death and MI were 5.4%, 9.5% and 14.7% in low, intermediate and high risk tertiles of the placebo pts, respectively, and 4.5%, 6.6% and 13.7% in comparable risk tertiles in perindopril pts, resulting in 17%, 30% and 6% risk reductions by perindopril in low , intermediate and high risk pts, respectively (interaction p-value 0.375). In revascularized pts, CV death and MI occurred in 4.2%, 7.1% and 12.9% in the low, intermediate and high risk placebo tertiles, respectively, and in 4.0%, 5.3% and 10.8% of comparable perindopril tertiles, resulting in a 5%, 26% and 16% risk reduction in favour of perindopril in the low, intermediate and high risk groups, respectively (interaction p-value 0.739).
Conclusions: Treatment benefit with perindopril is consistent among low, intermediate and high risk pts with normal LV function or previous revascularization without heterogeneity of treatment effect.
Keywords: ACE inhibitor, Coronary artery disease, Risk prediction