Abstract 14717: Double-blind, Randomized Comparison of Zofenopril vs. Ramipril in MI Patients Treated With ASA: The SMILE 4 Study and Subgroup Analysis
Background. ACE-inhibitors (ACEI's) are largely used for the treatment of patients with left ventricular dysfunction (LVD). Their efficacy has reported as unfavorably affected by the concomitant administration of ASA with differences among the drugs.
Methods. The primary objective of the SMILE IV study was the 1-year combined occurrence of death, hospitalization for CV causes (CV-Hx) or decrease in LVEF (>15%) in 771 patients with post-MI LVD (clinical CHF or EF<40%) randomly assigned to treatment with zofenopril (ZOF, n.389) 30-60 mg/day or ramipril (RAM,n.382) 5-10 mg/day in combination with ASA (100 mg/day) according to a double-blind study. The SMILE-IV study was a multinational trial including 7 European countries.
Results: Patients populations were comparable except for risk profile that was worse in patients treated with zofenopril. The primary outcome was significantly reduced in patients treated with ZOF vs. RAM (RR,95% CI: 0.70, 0.54-0.97;2p=0.028) as a result of a decrease in CV-Hx (RR,95% CI: 0.64,0.46-0.89;2p=0.009) and % with decline in LVEF% (RR,95% CI: 0.70, 0.54-0.97;2p=0.031) while mortality was comparable. Multivariate logistic regression analysis including all the significant univariate prognostic indicators showed that only Killip class 2-4 (p=0.0001) and ZOF treatment (p=0.04) remained significant after adjustment. The primary end-point was significantly reduced in some prespecified subgroups including: patients without prior CHD (RR,95% CI: 0.67,0.42-0.91:2p=0.01) DM (RR,95%CI: 0.61, 0.46-0.97,2p=0.019, baseline BP > 140 mmHg (RR,95% CI: 0.57,0.32-0.84, 2p=0.003) and preserved LV function at baseline (RR,95%CI: 0.60, 0.39-0.91,2p=0.016). A significantly smaller percentage of patients treated with zofenopril needed a concomitant treatment with more than 8 drugs (p= 0.021).
Conclusions: the SMILE IV study is the first trial directly comparing two ACEI's in patients with LVD. The results of the SMILE-IV study support a difference in the efficacy of various ACEI's when combined with ASA in post.MI patients with LV dysfunction and in particular in some subgroups of clinical interest. These findings might have some important implications for the future choice of ACEI's in patient with LVD and heart failure.
- © 2011 by American Heart Association, Inc.