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.