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 nonsignificant 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.