Effects of perindopril on long-term clinical outcome of patients with coronary artery disease and preserved left ventricular function

Background: The EUROPA trial has demonstrated that an ACE inhibitor perindopril, was able to significantly decrease the risk of major cardiac events in patients with stable coronary heart disease without apparent heart failure. Aim: To assess the long-term clinical outcome of patients with stable coronary heart disease and preserved left ventricular function (left ventricular ejection fraction (LVEF ≥ 40%). Methods: A retrospective evaluation of LVEF was performed in the EUROPA study population. Among the 12,218 patients of EUROPA, we identified 7096 (58%) patients who had LVEF measurement before randomization. The measurements were obtained mainly by echocardiography in 5214 cases (73%) or by angiography in 1470 cases (21%). Two groups of patients were studied: 6878 (97 %) patients with LVEF ≥ 40% (3429 received 8 mg of perindopril and 3449 received a placebo) and 218 patients (3%) with a LVEF < 40% (111 received perindopril and 107 a placebo). Results: The baseline characteristics of patients with documented LVEF were similar to the whole EUROPA population in terms of demographics, medical history, physical examination (heart rate, blood pressure), and medications at screening. The mean LVEF of this population was 57.0 ± 10.4%. In patients (n = 6878) with preserved LV function (LVEF ≥ 40%), there was a significant relative risk reduction of 16% of the primary endpoint (a composite of cardiovascular death, non-fatal myocardial infarction and resuscitated cardiac arrest) in the group treated with perindopril (8.3%) in comparison to the group treated with placebo (9.8%): Hazard ratio (HR) = 0.84 [95% CI: 0.72-0.99] p = 0.033). Similar results were obtained for the first secondary endpoint (total mortality, non-fatal myocardial infarction, hospital admission for unstable angina and cardiac arrest with successful resuscitation): HR = 0.85 [95% CI: 0.76-0.96] p = 0.008, for cardiovascular mortality and non-fatal MI: HR = 0.84 [95% CI: 0.72-0.99] p = 0.036. Similar benefits were observed in patients with an LVEF ≥ 40% and a history of previous myocardial infarction and in patients with an LVEF < 40%. Conclusions: LVEF was documented in 58% of the EUROPA study population and only 3% had an impaired LV function, confirming that EUROPA patients did not have asymptomatic LV dysfunction. Results in patients with preserved LV function are consistent with those of the whole EUROPA study population and perindopril 8 mg is beneficial in the broad spectrum of patients with stable coronary artery disease without evidence of heart failure.

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