Published Online
on December 10, 2007

A more recent version of this article appeared on January 1, 2008

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Submitted on December 18, 2006
Accepted on October 15, 2007

Effects of Angiotensin-Converting Enzyme Inhibition in Low-Risk Patients Early After Coronary Artery Bypass Surgery

Jean L. Rouleau MD^*, Wayne J. Warnica MD, Richard Baillot MD, Pierre J. Block MD, Sidney Chocron MD, PhD, David Johnstone MD, Martin G. Myers MD, Cristina-Dana Calciu MD, Sonia Dalle-Ave MD, Pierre Martineau PharmD, Christine Mormont PhD, Wiek H. van Gilst PhD, for the IMAGINE (Ischemia Management with Accupril post-bypass Graft via Inhibition of the coNverting Enzyme) Investigators

From the Research Center, Montreal Heart Institute and University of Montreal (J.L.R.), Montreal, Quebec, Canada; Department of Cardiology, Foothills Hospital, University of Calgary (W.J.W.), Calgary, Alberta, Canada; Department of Cardiology, Hôpital Laval, Laval University (R.B.), Quebec City, Quebec, Canada; Department of Cardiology, Academisch Ziekenhuis Vrije Universiteit (P.J.B.), Brussels, Belgium; Department of Cardiology, Université of Franche-Comté (S.C.), Besançon, France; Walter C. McKenzie Health Sciences Center, Queen Elizabeth II Hospital, Dalhousie University (D.J.), Halifax, Nova Scotia, Canada; Medical Division, Sunnybrook and Women’s College Health Science Centre, University of Toronto (M.G.M.), Toronto, Ontario, Canada; Medical Division, Pfizer Canada (C.D.C., P.M., C.M.), Montreal, Quebec, Canada; Medical Division, Pfizer Canada (S.D.A.), Toronto, Ontario, Canada; and Medical Center, University Medical Center, University of Groningen (W.H.v.G.), Groningen, the Netherlands.

^* To whom correspondence should be addressed. E-mail: jean.rouleau{at}umontreal.ca.

Background—Early after coronary artery bypass surgery (CABG), activation of numerous neurohumoral and endogenous vasodilator systems occurs that could be influenced favorably by angiotensin-converting enzyme inhibitors.

Methods and Results—The Ischemia Management with Accupril post-bypass Graft via Inhibition of the coNverting Enzyme (IMAGINE) trial tested whether early initiation (7 days) of an angiotensin-converting enzyme inhibitor after CABG reduced cardiovascular events in stable patients with left ventricular ejection fraction 40%. The trial was a double-blind, placebo-controlled study of 2553 patients randomly assigned to quinapril, target dose 40 mg/d, or placebo, who were followed up to a maximum of 43 months. The mean (SD) age was 61 (10) years. The incidence of the primary composite end point (cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction, coronary revascularization, unstable angina or heart failure requiring hospitalization, documented angina, and stroke) was 13.7% in the quinapril group and 12.2% in the placebo group (hazard ratio 1.15, 95% confidence interval 0.92 to 1.42, P=0.212) over a median follow-up of 2.95 years. The incidence of the primary composite end point increased significantly in the first 3 months after CABG in the quinapril group (hazard ratio 1.52, 95% confidence interval 1.03 to 2.26, P=0.0356). Adverse events also increased in the quinapril group, particularly during the first 3 months after CABG.

Conclusions—In patients at low risk of cardiovascular events after CABG, routine early initiation of angiotensin-converting enzyme inhibitor therapy does not appear to improve clinical outcome up to 3 years after CABG; however, it increases the incidence of adverse events, particularly early after CABG. Thus, early after CABG, initiation of angiotensin-converting enzyme inhibitor therapy should be individualized and continually reassessed over time according to risk.

Key words: cardiopulmonary bypass • coronary disease • inhibitors • trials • vasodilation

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