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

Abstract

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 coNvertingEnzyme (IMAGINE) trial tested whether early initiation (Յ7 days) of an angiotensin-converting enzyme inhibitor after CABG reduced cardiovascular events in stable patients with left ventricular ejection fraction Ն40%. 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, Pϭ0.212) 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, Pϭ0.0356). 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 angiotensinconverting 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. (Circulation. 2008;117:24-31.)

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease

“…797 Similarly, the IMAGINE (Ischemia Management With Accupril Post-Bypass Graft via Inhibition of the Converting Enzyme) study demonstrated no reduction in clinical outcomes in low-risk patients (LVEF Ͼ40%) with quinapril after surgical revascularization. 803 In a meta-analysis of ACE-inhibitor therapy versus placebo in 31 555 patients from HOPE, EUROPA, PEACE, and QUIET, ACE-inhibitor therapy produced 14% reductions in all-cause mortality and MI (both Pϭ0.0004), a 23% reduction in stroke (Pϭ0.0004), and a 7% reduction in revascularization procedures (Pϭ0.025) compared with placebo. 796 Although the cited studies involved a variety of ACE inhibitors that differ with regard to structure, bioavailability, potency, receptor-binding characteristics, tissue distribution, metabolism, and excretion properties, there is little evidence that these differences are associated with therapeutic advantages.…”

2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery

“…The IMAGINE (Ischemia Management With Accupril Post Bypass Graft via Inhibition of Angiotensin Converting Enzyme) study failed to show a beneficial effect of postoperative ACE inhibitor therapy 3 years after CABG, instead noting an increase in adverse events, particularly recurrent angina in the first 3 months of therapy. 630 A subanalysis of the data from patients enrolled in EUROPA (European Trial on the Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease) with previous revascularization (CABG or PCI no sooner than 6 months before enrollment) suggested a primary and secondary prevention benefit over a 4.2-year follow-up period; however, an analysis of the data from almost 3000 patients in the PREVENT IV (PRoject of Ex-vivo Vein graft ENgineering via Transfection) trial, all of whom were taking either ACE inhibitors or ARBs at the time of hospital discharge, failed to demonstrate a significant reduction in death or MI after 2 years of follow-up in "ideal" candidates (based on ACCF/AHA/HRS guidelines) (HR: 0.87; 95% CI: 0.52 to 1.45; PϭNS), whereas significance was achieved in "non-ideal" candidates (HR: 1.64; 95% CI: 1.00 to 2.68; Pϭ0.05). Smoking cessation after CABG is associated with a substantial reduction in subsequent MACE, including MI and death.…”

Secondary Prevention After Coronary Artery Bypass Graft Surgery

“…The incidence of the primary composite end point increased significantly in the first 3 months after CABG in the quinapril group (P=0.04), and adverse events (such as hypotension) were also increased in the quinapril group, particularly during the first 3 postoperative months. 233 Thus, in this select trial population, routine ACE inhibitor therapy led to more harm than benefit when initiated early after CABG.…”

“…[244][245][246] The routine initiation of an ACE inhibitor early after CABG is not recommended for patients with an EF >40%. 233 However, it is unlikely that surgical revascularization mitigates the benefits of an ACE inhibitor in the post-CABG patient with a persistently reduced EF.…”