Effects of zofenopril on myocardial ischemia in post–myocardial infarction patients with preserved left ventricular function: The Survival of Myocardial Infarction Long-term Evaluation (SMILE)–ISCHEMIA study

Background The aim of the study was to investigate the cardioprotective effects of the angiotensin-converting enzyme inhibitor zofenopril in post–myocardial infarction (MI) patients with preserved left ventricular function (LVF). Methods Three hundred forty-nine post-MI patients with preserved LVF (LV ejection fraction >40%) were treated for 6 months with zofenopril 30 to 60 mg (n = 177) or placebo (n = 172) according to a double-blind, randomized study design. The primary end point of the study was the combined occurrence of significant ST-T abnormalities on ambulatory electrocardiography (ECG), ECG abnormalities or symptoms of angina during standard exercise test, recurrence of MI, and need for revascularization procedures for angina. Results The primary end point occurred in 20.3% of zofenopril-treated and 35.9% of placebo-treated patients ( P = .001), despite no differences in blood pressure control, LVF, and concomitant therapy. ST-T depression during ambulatory ECG occurred in 22.7% of patients treated with placebo and 10.7% of those undergoing ACE-inhibition treatment ( P = .027). ST-T depression in response to exercise test occurred in 14.2% and 26.7% of patients treated with zofenopril or placebo, respectively, ( P = .024), with a lower proportion of zofenopril-treated patients who complained of anginal pain (4.7 vs 14.3%; P = .017), significant ST depression (14.2 vs 26.7%; P = .024), and major ventricular arrhythmias (3.8 vs 10.5%; P = .048). The rate of major cardiovascular events was reduced in patients treated with ACE inhibitor, with a lower rate of development and progression of congestive heart failure. Conclusions The results of the SMILE-ISCHEMIA study support the cardioprotective role of zofenopril when given to patients with normal LVF after acute MI.