Cost-effectiveness of zofenopril in patients with left ventricular systolic dysfunction after acute myocardial infarction: a post hoc analysis of SMILE-4

Claudio Borghi,1 Ettore Ambrosioni,1 Stefano Omboni,2 Arrigo FG Cicero,1 Stefano Bacchelli,1 Daniela Degli Esposti,1 Salvatore Novo,3 Dragos Vinereanu,4 Giuseppe Ambrosio,5 Giorgio Reggiardo,6 Dario Zava7 1Unit of Internal Medicine, Policlinico S Orsola, University of Bologna, Bologna, Italy; 2Italian Institute of Telemedicine, Varese, Italy; 3Division of Cardiology, University of Palermo, Palermo, Italy; 4University and Emergency Hospital, Bucharest, Romania; 5Division of Cardiology, University of Perugia, Perugia, Italy; 6Mediservice, Milano, Italy; 7Istituto Lusofarmaco d'Italia SpA, Peschiera Borromeo, Italy Background: In SMILE-4 (the Survival of Myocardial Infarction Long-term Evaluation 4 study), zofenopril + acetylsalicylic acid (ASA) was superior to ramipril + ASA in reducing the occurrence of major cardiovascular events in patients with left ventricular dysfunction following acute myocardial infarction. The present post hoc analysis was performed to compare the cost-effectiveness of zofenopril and ramipril. Methods: In total, 771 patients with left ventricular dysfunction and acute myocardial infarction were randomized in a double-blind manner to receive zofenopril 60 mg/day (n = 389) or ramipril 10 mg/day (n = 382) + ASA 100 mg/day and were followed up for one year. The primary study endpoint was the one-year combined occurrence of death or hospitalization for cardiovascular causes. The economic analysis was based on evaluation of cost of medications and hospitalizations and was applied to the intention-to-treat population (n = 716). Cost data were drawn from the National Health Service databases of the European countries participating in the study. The incremental cost-effectiveness ratio was used to quantify the cost per event prevented with zofenopril versus ramipril. Results: Zofenopril significantly (P = 0.028) reduced the risk of the primary study endpoint by 30% as compared with ramipril (95% confidence interval, 4%–49%). The number needed to treat to prevent a major cardiovascular event with zofenopril was 13 less than with ramipril. The cost of drug therapies was higher with zofenopril (328.78 Euros per patient per year, n = 365) than with ramipril (165.12 Euros per patient per year, n = 351). The cost related to the occurrence of major cardiovascular events requiring hospitalization averaged 4983.64 Euros for zofenopril and 4850.01 Euros for ramipril. The incremental cost-effectiveness ratio for zofenopril versus ramipril was 2125.45 Euros per event prevented (worst and best case scenario in the sensitivity analysis was 3590.09 and