Perindopril and beta-blocker for the prevention of cardiac events and mortality in stable coronary artery disease patients: A EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) subanalysis

Background beta-Blockers relieve angina/ischemia in stable coronary artery disease (CAD), and angiotensin-converting enzyme inhibitors prevent CAD outcomes. In EUROPA, the angiotensin-converting enzyme inhibitor perindopril reduced cardiovascular outcomes in low-risk stable CAD patients over 4.2 years. This post hoc analysis examined whether the addition of perindopril to beta-blocker in EUROPA had additional benefits on outcomes compared with standard therapy including beta-blocker. Methods EUROPA was a multicenter, double-blind, placebo-controlled, randomized trial in patients with documented stable CAD. Randomized EUROPA patients who received beta-blocker at baseline were identified, and the effect on cardiovascular outcomes of adding perindopril or placebo was analyzed. Endpoints were the same as those in EUROPA. Results At baseline, 62% (n = 7534 [3789 on perindopril and 3745 on placebo]) received beta-blocker. Treatment with perindopril/beta-blocker reduced the relative risk of the primary end point (cardiovascular death, nonfatal myocardial infarction, and resuscitated cardiac arrest) by 24% compared with placebo/beta-blocker (HR, 0.76; 95% CI, 0.64-0.91; P = .002). Addition of perindopril also reduced fatal or nonfatal myocardial infarction by 28% (HR, 0.72; 95% CI, 0.59-0.88; P = .001) and hospitalization for heart failure by 45% (HR, 0.55; 95% CI, 0.33-0.93; P = .025). Serious adverse drug reactions were rare in both groups, and cardiovascular death and hospitalizations occurred less often with perindopril/beta-blocker. Conclusions The addition of perindopril to beta-blocker in stable CAD patients was safe and resulted in reductions in cardiovascular outcomes and mortality compared with standard therapy including beta-blocker.