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Risk Assessment and Risk Reduction by Perindopril in Patients With Normal Left Ventricular Function or Previous Revascularization in the EUROPA Study
Authors:
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
Topic(s):
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
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