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

SUMMARYObjective: 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.

Efficacy of Zofenopril Compared With Placebo and Other Angiotensin-converting Enzyme Inhibitors in Patients With Acute Myocardial Infarction and Previous Cardiovascular Risk Factors: A Pooled Individual Data Analysis of 4 Randomized, Double-blind, Controlled, Prospective Studies

“…7,8 Thus, the knowledge of the clinical profiles of ACE inhibitors in these settings is essential. For example, congestive heart failure is frequently evident in post-AMI patients and significantly contributes to a high mortality and morbidity risk; the presence of renal dysfunction is a further negative complication increasing the 1-month and 1-year mortality and adverse cardiac events.…”

“…For this aim, the individual data were first included in a previous pooled analysis 5 where the cumulative efficacy of zofenopril on CV mortality and morbidity in post-AMI patients was evaluated by increasing the robustness of the evidence related to the prevention of major CV events. The SMILE project further encompassed in-depth analyses of patient subgroups such as patients with diabetes 6,7 or hypertension. 8,9 …”

Efficacy and Safety of Zofenopril Versus Ramipril in the Treatment of Myocardial Infarction and Heart Failure: A Review of the Published and Unpublished Data of the Randomized Double-Blind SMILE-4 Study

“…In the SMILE-4 study, in which diabetic patients represented 19% of the population, zofenopril had a larger effect than ramipril in reducing the combined occurrence of death or hospitalization in patients with diabetes (OR 0.56, 95% CI 0.18–1.73), although the between-treatment difference was not statically significant ( p = 0.313). Conversely, the reduction in the rate of hospital admission for CV causes was significantly larger under zofenopril (OR 0.38, 95% CI 0.15–0.95, p = 0.038) (Table 3 ) [ 26 ]. The larger effect of zofenopril over ramipril was particularly evident in patients with uncontrolled blood glucose (≥ 126 mg/dL), regardless of the previous diagnosis of diabetes (Fig.…”

Pulse pressure index as a discriminator of predicting the cardiovascular events in hypertensive patients treated with drugs acting on angiotensinogen-angiotensin pathway..

“…J. 15 (1), 2019 (CVEs) [3]. Ramipril and perindopril have a protective effect against cerebrovascular accidents and they significantly reduced the recurrence of stroke [4].…”