A meta-analysis of three key trials found overall benefit despite one discrepant set of results.
Angiotensin-converting–enzyme (ACE) inhibitors reduce rates of mortality, hospitalization for heart failure, and myocardial infarction in patients with heart failure or left ventricular systolic dysfunction (LVSD). Do ACE inhibitors have similar benefits in patients with coronary artery disease (CAD) but without heart failure or LVSD? Of three large randomized, placebo-controlled trials in patients with known CAD, two (HOPE and EUROPA) showed fewer cardiovascular events with ACE inhibitors, but a third (PEACE) did not. Researchers now present a meta-analysis of these three trials, which had a combined enrollment of 29,805 and a mean follow-up of 4.5 years. (See Journal Watch Jan 25 2000 for HOPE; Journal Watch Oct 21 2003 for EUROPA; and Journal Watch Nov 19 2004 for PEACE.)
The composite outcome of death, MI, or stroke was less likely in patients taking ACE inhibitors than in those who were not (odds ratio, 0.82). The individual endpoints of death, MI, stroke, admission for heart failure, and coronary artery bypass graft were also significantly less likely. In a combined analysis of the HOPE and EUROPA trials, similar reductions were seen at varying levels of baseline risk and in various other subgroups of patients.
Comment: The authors conclude that "the use of ACE inhibitors should be considered in all patients with vascular disease" and attribute the discrepant results of the PEACE study to inadequate power. Alternatively, editorialists ascribe the discrepancy to a difference in subjects: PEACE participants had lower risks and used more concomitant protective medications. A point of controversy, not addressed in this analysis, is the extent to which the benefit of ACE inhibitors is independent of blood pressure lowering. In any case, ACE inhibitors appear to be worthwhile for patients with established CAD.
— Bruce Soloway, MD
Published in Journal Watch September 26, 2006
Citation(s):
Dagenais GR et al. Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: A combined analysis of three trials. Lancet 2006 Aug 12; 368:581-8.