ORIGINAL ARTICLE Efficacy of zofenopril in combination with amlodipine in patients with acute myocardial infarction: a pooled individual patient data analysis of four randomized, double-blind, controlled, prospective studies Claudio Borghi a , Stefano Omboni b,c , Giorgio Reggiardo d , Stefano Bacchelli a , Daniela Degli Esposti a and and Ettore Ambrosioni a ; on behalf of the SMILE (Survival of Myocardial Infarction Long-Term Evaluation) Working Project a Unit of Internal Medicine, Policlinico S. Orsola, University of Bologna, Bologna, Italy; b Clinical Research Unit, Italian Institute of Telemedicine, Varese, Italy; c Scientific Research Department of Cardiology, Science and Technology Park for Biomedicine, Sechenov First Moscow State Medical University, Moscow, Russian Federation; d Mediservice S.r.l., Agrate Brianza, Italy ABSTRACT Objective: In the four SMILE (Survival of Myocardial Infarction Long-Term Evaluation) studies, early administration of zofenopril in acute myocardial infarction (AMI) showed beneficial effects as com- pared to placebo and other angiotensin converting enzyme inhibitors (ACEIs). This study investigated whether the concomitant administration of the dihydropyridine calcium channel-blocker amlodipine may improve zofenopril efficacy to prevent cardiovascular events in post-AMI patients. Methods: This was a post-hoc analysis of pooled individual patient data from the four large random- ized SMILE studies. The primary endpoint was the 1-year combined occurrence of death or hospitaliza- tion for cardiovascular causes. Results: In total, 3488 patients were considered, 303 (8.7%) treated with concomitant amlodipine. Baseline systolic blood pressure and prevalence of metabolic syndrome were higher in amlodipine treated patients. The 1-year occurrence of major cardiovascular outcomes was significantly reduced in patients receiving concomitant treatment with amlodipine (hazard ratio, HR ¼ 0.66; and 95% confi- dence interval, CI ¼ 0.44–0.98; p ¼ .039). After accounting for treatment with amlodipine, the risk of cardiovascular events was significantly reduced with zofenopril compared to placebo (HR ¼ 0.78; 95% CI ¼ 0.63–0.97; p ¼ .026]. Among ACEI-treated patients, the zofenopril plus amlodipine combination reduced the risk of cardiovascular events by 38%, compared to the combination of other ACEIs plus amlodipine [HR ¼ 0.76; 95% CI ¼ 0.61–0.94); p ¼ .013). The prognostic benefit of concomitant treatment with zofenopril plus amlodipine was independent from blood pressure lowering. Conclusions: Zofenopril had a positive impact on prognosis in post-AMI patients, compared to other ACEIs. Concomitant administration of amlodipine may help to reduce the risk of cardiovascular events at 1 year. ARTICLE HISTORY Received 5 December 2017 Revised 21 June 2018 Accepted 29 June 2018 KEYWORDS Acute myocardial infarction; Drug therapy; Angiotensin- converting enzyme inhibitors; Amlodipine; Cardiovascular risk Introduction Cardiovascular disease (CVD) is a leading cause of morbidity and mortality, despite improvements in outcomes 1 . The prevalence of many risk factors, including diabetes and obes- ity, has been progressively increasing, and measures to pre- vent CVD are now mandatory 2,3 . In 2016, the European Society of Cardiology released specific guidelines on CVD prevention, as defined as a coordinated set of actions, at the population level or targeted at an individual, that are aimed at eliminating or minimizing the impact of CVDs and their related disabilities 1 . According to these guidelines, subjects with previous acute myocardial infarction (AMI), acute coron- ary syndrome, coronary revascularization and other arterial revascularization procedures, stroke and transient ischemic attack are at very high risk of CVD, and frequently require pharmacological treatments, in combination with lifestyle changes 1 . In patients at high risk, the early control of blood pressure is desirable 1 ; the combination of several drugs with complementary mechanism of actions is often needed to achieve this goal 1 . In patients in the acute phase of AMI, the recommended pharmacological treatments to be initiated within the first 24-h are oral beta-blockers, non-dihydropyri- dine calcium channel blockers (CCBs) (in the absence of acute LVD or HF), dihydropyridine CCBs (when beta-blockers are contraindicated), and angiotensin converting enzyme inhibitors (ACEIs) (angiotensin receptor blockers if ACEIs are non-tolerated). These drugs have proved to reduce mortality in AMI and should be continued indefinitely when the patient is stabilized, in order to maintain a proper cardiac function and achieve control of CV risk factors, including blood pressure. Based on results from clinical trials, the most rational combinations for long-term management of post-AMI CONTACT Claudio Borghi claudio.borghi@unibo.it Divisione di Medicina Interna, Policlinico S.Orsola, Via Massarenti 9, 40138 Bologna, Italy ß 2018 Informa UK Limited, trading as Taylor & Francis Group www.cmrojournal.com CURRENT MEDICAL RESEARCH AND OPINION 2018, VOL. 34, NO. 10, 1869–1874 https://doi.org/10.1080/03007995.2018.1496076 Article ST-0763.R1/1496076 All rights reserved: reproduction in whole or part not permitted