Double-blind comparison between zofenopril and lisinopril in patients with acute myocardial infarction: results of the Survival of Myocardial Infarction Long-term Evaluation-2 (SMILE-2) study

Background Angiotensin-converting enzyme (ACE) inhibitors have been reported to be effective in placebo-controlled trials in various subsets of patients with acute myocardial infarction (MI). However, no direct comparisons have been performed between different ACE inhibitors in the same patient population.Methods This phase III, double-blind, parallel-group, multicenter study compared the safety and efficacy of zofenopril and lisinopril in 1024 thrombolyzed patients with acute MI. Patients, aged 18 to 75 years, were randomized to receive oral zofenopril (30-60 mg/day) or lisinopril (5-10 mg/day), starting within 12 hours of completion of thrombolytic therapy and continuing for 42 days. The primary study end point was the incidence of severe hypotension (systolic blood pressure <90 mm Hg), either cumulative or drug-related. Secondary end points included additional safety and efficacy parameters.Results The overall incidence of severe hypotension was slightly 5more reduced with zofenopril (10.9%) than with lisinopril (11.7%, P = .38). The incidence of drug-related severe hypotension was slightly but significantly lower with zofenopril than with lisinopril (6.7 vs 9.8%, 2-tailed P = .048). The 6-week mortality rate was 3.2% in the zofenopril group and 4.0% in the lisinopril group (P = .38), and no significant differences were observed in the incidence of major cardiovascular complications or any safety variables between the 2 ACE inhibitors.Conclusions The SMILE-2 study demonstrates that both zofenopril and lisinopril are safe and associated with a rather low rate of severe hypotension when given in accordance with a dose-titrated scheme to thrombolyzed patients with acute MI. These findings could have a positive clinical impact and increase the proportion of patients with acute MI who can be safely treated with ACE inhibitors. (Am Heart J 2003;145:80-7.)