In the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) studies, early administration of zofenopril after acute myocardial infarction (AMI) was prognostically beneficial as compared to placebo and other angiotensin-converting enzyme inhibitors (ACEIs), such as lisinopril and ramipril. Here, we investigated whether zofenopril efficacy could be affected by a concomitant use of thiazide diuretics (TDs).
This was a post hoc analysis of pooled individual patient data from the SMILE studies. Patients treated with other diuretics than TDs were excluded. The primary study endpoint was the 1-year combined occurrence of death or hospitalization for CV causes, with or without TD.
Among 2,995 patients, 263 (8.8%) were treated with a combination including a TD (TD+), whereas 2,732 (91.2%) were not treated with any diuretic (TD−). Proportions of subjects who were treated with TD were equally distributed ( p=0.774) within the placebo, zofenopril, and other ACEIs groups. The 1-year risk of major cardiovascular events was similar in TD+ (18.3%) and TD− (16.8%) patients (hazard ratio [HR] 1.04; 95% CI 0.74–1.45; p=0.838). After stratifying per concomitant treatment and TD, the 1-year risk of CV events was significantly lower with zofenopril than with placebo (HR 0.70; 95% CI 0.55–0.88; p=0.002) and other ACEIs (HR 0.58; 95% CI 0.46–0.74; p=0.0001). Treatment with ACEIs and TD as concomitant therapy was associated with a larger blood pressure (BP) reduction ( p=0.0001 for systolic BP and p=0.045 for diastolic BP).