Cardioprotective role of zofenopril in patients with acute myocardial infarction: a pooled individual data analysis of four randomised, double-blind, controlled, prospective studies

BACKGROUND: Early administration of zofenopril following acute myocardial infarction (AMI) proved to be prognostically beneficial in the four individual randomised, double-blind, parallel-group, prospective SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies. In the present analysis, we evaluated the cumulative efficacy of zofenopril by pooling individual data from the four SMILE studies. METHODS: 3630 patients with AMI were enrolled and treated for 6–48 weeks with zofenopril 30–60 mg/day (n=1808), placebo (n=951), lisinopril 5–10 mg/day (n=520) or ramipril 10 mg/day (n=351). The primary study end point of this pooled analysis was set to 1 year combined occurrence of death or hospitalisation for cardiovascular (CV) causes. RESULTS: Occurrence of major CV outcomes was significantly reduced with zofenopril versus placebo (−40%; HR=0.60, 95% CI 0.49 to 0.74; p=0.0001) and versus the other ACE inhibitors (−23%; HR=0.77, 0.63 to 0.95; p=0.015). The risk reduction observed under treatment with the other ACE inhibitors was nearly statistically significant (−22%; HR=0.78, 0.60 to 1.02; p=0.072). The benefit of zofenopril versus placebo was already evident after the first 6 weeks of treatment (−28%; HR=0.72, 0.54 to 0.97; p=0.029), while this was not the case for the other ACE inhibitors (−19%; HR=0.81, 0.57 to 1.17; p=0.262). In this early phase of treatment, zofenopril showed a non-significant trend towards a larger reduction in CV events versus the other ACE inhibitors (−11%; HR=0.89, 0.69 to 1.15; p=0.372). CONCLUSIONS: The pooled data analysis from the SMILE Programme confirms the favourable effects of zofenopril treatment in patients with post-AMI and its long-term benefit in terms of prevention of CV morbidity and mortality.