Efficacy of Ace Inhibition with Zofenopril, Lisinopril, or Ramipril in Postacute Myocardial Infarction Patients With or Without Metabolic Syndrome: A Pooled Individual Data Analysis of Four Randomized, Double-Blind, Controlled, Prospective Studies

Background: The metabolic syndrome (MS) is a clustering of different cardiovascular (CV) risk factors, which further enhances the risk of death and CV complications in post-acute myocardial infarction (AMI) patients. In the present meta-analysis of individual data of the four randomized, prospective SMILE studies, we evaluated the efficacy of zofenopril vs. lisinopril, ramipril, and placebo on 1-year CV morbidity and mortality, according to the presence (+) or absence (−) of the MS. Methods: 2203 (63.2%) of the 3488 patients were classified as MS+, 1285 (36.8%) as MS−. Five hundred two MS+ and 380 MS− were treated with placebo, 1134 and 608 with zofenopril 30–60 mg/die, 340 and 175 with lisinopril 5–10 mg/die, and 227 and 122 with ramipril 10 mg/die. Treatment was continued for 6 to 48 weeks. Results: The 1-year risk of a major CV event was similar (P = 0.420) in MS+ (18.1%) and MS− (18.0%) patients [HR and 95% confidence interval: 0.92 (0.76–1.12)]. After accounting for MS+/MS−, the 1-year risk of CV events vs. placebo was significantly lower under zofenopril [0.79 (0.63–0.97); P = 0.028] and lisinopril [0.65 (0.47–0.89); P = 0.007], but larger under ramipril [2.57 (1.94–3.93); P = 0.0001]. Treatment with zofenopril was associated with a statistically significant (P = 0.0001) reduction in CV risk as compared with the other angiotensin-converting enzyme inhibitors [MS+: 0.52 (0.42–0.66); MS−: 0.52 (0.38–0.73)]. Conclusions: In post-AMI patients with MS, zofenopril treatment is associated with a clinically relevant reduction in long-term CV morbidity and mortality, compared with placebo, with an efficacy similar to lisinopril, but better than ramipril.