title: Zofenopril and Ramipril in Combination with Acetyl Salicylic Acid in Postmyocardial Infarction Patients with Left Ventricular Systolic Dysfunction: A Retrospective Analysis of the SMILE-4 Randomized, Double-Blind Study in Diabetic Patients.
abstract: OBJECTIVE
  In the SMILE-4 study, zofenopril + acetyl salicylic acid (ASA) was more effective than ramipril + ASA on 1-year prevention of major cardiovascular events (MACE) in patients with acute myocardial infarction complicated by left ventricular dysfunction. In this retrospective analysis, we evaluated drug efficacy in subgroups of patients, according to a history of diabetes mellitus.
  
  
  METHODS
  The primary study endpoint was 1-year combined occurrence of death or hospitalization for cardiovascular causes. Diabetes was defined according to medical history (previous known diagnosis).
  
  
  RESULTS
  A total of 562 of 693 (81.0%) patients were classified as nondiabetics and 131 (18.9%) as diabetics. The adjusted rate of MACE was lower under zofenopril than under ramipril in both nondiabetics [27.9% vs. 34.9% ramipril; odds ratio, OR and 95% confidence interval: 0.55 (0.35, 0.86)] and diabetics [30.9% vs. 41.3%; 0.56 (0.18, 1.73)], although the difference was statistically significant only for the nondiabetic group (P = 0.013). Zofenopril was superior to ramipril as regards to the primary study endpoint in the subgroup of 157 patients with uncontrolled blood glucose (≥ 126 mg/dL), regardless of a previous diagnosis of diabetes [0.31 (0.10, 0.90), P = 0.030]. Zofenopril significantly reduced the risk of hospitalization for cardiovascular causes in both nondiabetics [0.64 (0.43, 0.96), P = 0.030] and diabetics [0.38 (0.15, 0.95), P = 0.038], whereas it was not better than ramipril in terms of prevention of cardiovascular deaths.
  
  
  CONCLUSIONS
  This retrospective analysis of the SMILE-4 study confirmed the good efficacy of zofenopril plus ASA in the prevention of long-term MACE also in the subgroup of patients with diabetes mellitus.
authors.affiliation: Unit of Internal Medicine, Policlinico S. Orsola, University of Bologna, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Borghi
authors.affiliation: Clinical Research Unit, Italian Institute of Telemedicine, Varese, Italy.
authors.forename: Stefano
authors.identifier: http://orcid.org/0000-0002-7124-2096
authors.initials: S
authors.lastname: Omboni
authors.affiliation: Division of Cardiology, University of Palermo, Palermo, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Novo
authors.affiliation: University and Emergency Hospital, Bucharest, Romania.
authors.forename: Dragos
authors.initials: D
authors.lastname: Vinereanu
authors.affiliation: Division of Cardiology, University of Perugia, Perugia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ambrosio
authors.affiliation: Unit of Internal Medicine, Policlinico S. Orsola, University of Bologna, Bologna, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Ambrosioni
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage*; D002216:Captopril / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D058065:Diabetic Cardiomyopathies / Q000150:complications*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000209:etiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D017257:Ramipril / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D013599:Systole; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; C044958:zofenopril; D002216:Captopril; D017257:Ramipril; D001241:Aspirin
keywords: Acetyl salicylic acid; Acute myocardial infarction; Angiotensin-converting enzyme inhibitors; Diabetes mellitus; Left ventricular dysfunction; Ramipril; Zofenopril