Overview of large randomized trials of ACE inhibitors in patients with stable vascular disease without left ventricular systolic dysfunction or heart failure, in the context of previous large trials

Abstract

Clinical CardiologyVolume 29, Issue 12 p. 549-549 Progress in Clinical TrialsOpen Access Overview of large randomized trials of ACE inhibitors in patients with stable vascular disease without left ventricular systolic dysfunction or heart failure, in the context of previous large trials First published: 18 December 2006 https://doi.org/10.1002/clc.20031AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Abstract Presenter GR Dagenais, MD, at the 2006 World College of Cardiology Background ACE inhibitors reduce cardiovascular (CV) mortality and morbidity in patients with heart failure or left ventricular systolic dysfunction (LVSD). Three large trials, HOPE (ramipril), EUROPA (perindopril) and PEACE (trandolapril), have assessed their impact in stable patients without these conditions but with atherosclerosis. Among these trials, only PEACE failed to meet its primary outcome (4% relative risk reduction in CV death, nonfatal MI or coronary revascularization, p = 0.043). Objective To determine (i) if there is any consistency with which ACE inhibitors reduce total mortality and fatal and nonfatal CV events in these trials and (ii) to determine if the benefits vary among patients with varying levels of risks or by ancillary treatments. Methodology Data were assessed from HOPE, EUROPA, PEACE and from five other trials carried out among patients with heart failure and LVSD: SOLVD-T, SOLVD-P, SAVE, AIRE and TRACE. Antiplatelet therapy consisted of aspirin at 81–325 mg daily. Study Populations HOPE, EUROPA and PEACE included nearly 30,000 patients. Age, blood pressure and diabetes rates were higher in HOPE. More patients in PEACE received lipid-lowering agents, but it also had more patients with prior PCI or CABG surgery. Results All-cause mortality was 6.1 vs. 6.9%, 7.2 vs. 8.1% and 10.4 vs. 12.2% for EUROPA, PEACE and HOPE, respectively. Results across all the eight trials were consistent in that they all revealed reduced all-cause mortality for ACE inhibition vs. placebo. In the three trials, the overall all-cause mortality odds ratio was 0.86 for those without heart failure or LVSD and 0.80 for those with these problems. Of the 12 trials, noted in the Methodology Section, only PEACE failed to show any reduction in nonfatal MI. There was reduced stroke in EUROPA, PEACE and HOPE (OR 0.77) but not in the other trials (OR 0.96). Conclusions This review of 30,000 patients without any known heart failure or LVSD demonstrates consistency and clear benefits for ACE inhibition on different outcomes. In the 12,000 patients with heart failure or LVSD, there was a consistent fourfold risk reduction across a broad range of outcomes except stroke. In patients with coronary artery disease, it is unlikely that the benefits of ACE inhibition will vary among patients with varying levels of risks or by ancillary treatments. ACE inhibition should be considered in all patients with any evidence of vascular atherosclerotic disease. Comment (Gilles R Dagenais, MD) PEACE results appear to differ, most likely because the trial was underpowered and used a single soft endpoint (coronary revascularization). (Discussant: Nicholas Danchin, MD, Canada) The difference in the results of PEACE from that of HOPE and EUROPA is possibly accounted for by a lower risk in the PEACE population, but more likely due to insufficient doses of trandolapril. Copyright © 2006 Wiley Periodicals, Inc. Volume29, Issue12December 2006Pages 549-549 RelatedInformation