Randomised comparison of zofenopril and ramipril plus acetylsalicylic acid in postmyocardial infarction patients with left ventricular systolic dysfunction: a post hoc analysis of the SMILE-4 Study in patients according to levels of left ventricular ejection fraction at entry.
Conflicting evidence exists on the benefits of treating patients with coronary artery disease and preserved left ventricular ejection fraction (LVEF) with an ACE inhibitor. This retrospective analysis of the SMILE-4 Study sought to compare the efficacy of zofenopril 60 mg plus acetylsalicylic acid (ASA) versus ramipril 10 mg plus ASA 100 mg in patients with acute myocardial infarction (AMI) and heart failure, according to an impaired or preserved LVEF.



The primary study end point was 1-year combined occurrence of death or hospitalisation for cardiovascular causes. A preserved LVEF was defined by a baseline LVEF >40% and an impaired one by an LVEF ≤40%.



448 patients (63%) had preserved and 262 (37%) had impaired LVEF. The primary end point occurred in 125 patients with preserved (28%) and 106 patients with impaired LVEF (41%, p=0.001). In the first group, the rate of major cardiovascular events was significantly lower under zofenopril than under ramipril (23% vs 33%; OR and 95% CI 0.60, 0.39 to 0.91; p=0.016). This was also the case for patients with impaired LVEF, though between-group difference was not statistically significant (38% zofenopril vs 44% ramipril; OR 0.77, 0.47 to 1.26; p=0.297). LVEF values significantly (p<0.0001) increased during the follow-up in both subsets with no between-treatment differences. However, improvement rates in LVEF (increase ≥5%) were higher in patients with impaired LVEF (72% vs 61%, p=0.006).



In the SMILE-4 Study, the cardiovascular outcome of patients with post-AMI with preserved LVEF was more favourable in the zofenopril than in the ramipril treatment group.



EudraCT Number: 2004-001150-88 (http://www.clinicaltrialsregister.eu); Italian Ministry of Health Code: GUIDOTT_III_2004_001 (https://oss-sper-clin.agenziafarmaco.it).
Unit of Internal Medicine , Policlinico S. Orsola, University of Bologna , Bologna , Italy.
Claudio
C
Borghi
Italian Institute of Telemedicine , Varese , Italy.
Stefano
S
Omboni
Unit of Internal Medicine , Policlinico S. Orsola, University of Bologna , Bologna , Italy.
Arrigo Fg
AF
Cicero
Unit of Internal Medicine , Policlinico S. Orsola, University of Bologna , Bologna , Italy.
Stefano
S
Bacchelli
Unit of Internal Medicine , Policlinico S. Orsola, University of Bologna , Bologna , Italy.
Daniela
D
Degli Esposti
Division of Cardiology , University of Palermo , Palermo , Italy.
Salvatore
S
Novo
University and Emergency Hospital , Bucharest , Romania.
Dragos
D
Vinereanu
Division of Cardiology , University of Perugia , Perugia , Italy.
Giuseppe
G
Ambrosio
Unit of Internal Medicine , Policlinico S. Orsola, University of Bologna , Bologna , Italy.
Ettore
E
Ambrosioni
acute myocardial infarction; angiotensin-converting enzyme inhibitors; left ventricular dysfunction; left ventricular ejection fraction