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Patterns of Use of Perioperative Angiotensin-Converting Enzyme Inhibitors in Coronary Artery Bypass Graft Surgery With Cardiopulmonary Bypass: Effects on In-Hospital Morbidity and Mortality
Study Questions:
Does use of angiotensin-converting enzyme inhibitor (ACEI) in the perioperative period in patients undergoing coronary artery bypass surgery (CABG) with cardiopulmonary bypass (CPB) have an effect on in-house morbidity and mortality?
Methods:
This was a prospective but nonrandomized multicenter trial. Data were available from 4,224 patients undergoing CABG with CPB, including 1,838 receiving ACEI therapy prior to surgery and 2,386 (56.5%) without preoperative ACEI. Decisions to continue, add, or discontinue ACEI were made by individual clinicians based on practice patterns. Outcomes which occurred >48 hours after surgery were tabulated, and included cardiac (myocardial infarction, congestive heart failure, or cardiac death), cerebrovascular (stroke, encephalopathy, or death from stroke), renal (dysfunction or failure), or other (such as gastrointestinal, infectious, pulmonary, or death of any other cause). The primary endpoint of the study was the composite outcome of cardiac, cerebral, and renal events and in-hospital death.
Results:
Patients on ACEI preoperatively had a higher prevalence of congestive heart failure (12.9% vs. 4.6%), myocardial infarction within 90 days (21.9% vs. 10.6%), hypertension (79.2% vs. 58.5%), creatine >1.3 mg/dl (20.2% vs.12.8%), and diabetes (37.6% vs. 25%) (all comparisons p < 0.001). EuroSCORE and APACHE II risk indexes were higher in those on ACEI than those not on ACEI. Based on clinical decisions to continue, withdraw, or add an ACEI, four groups of patients were identified, including 915 with continuation of preoperative ACEI, 923 with ACEI withdrawn at the time of surgery, 343 with ACEI added, and 2,043 with no ACEI exposure pre- or postoperatively. After propensity score and APACHE II adjustments, continuous use of ACEI was associated with 31% lower odds of the composited endpoint as well as a 36% lower odds of a cardiovascular event (both p < 0.006). Odds ratios for the composited outcome were 0.58 in the continuation versus no ACEI subgroup, 0.58 in the addition versus no ACEI subgroup, 1.70 in the withdrawal versus no ACEI subgroup, and 0.58 in the continuation versus withdrawal subgroup (all comparisons p < 0.006). In-hospital death occurred in 0.8% of the no ACEI subgroup, 1.5% in the continuation subgroup, 1.9% in the addition subgroup, and 3.0% in the withdrawal subgroup (all comparisons p = not significant).
Conclusions:
Withdrawal of ACEI after CABG is associated with a significant increase in nonfatal in-hospital cardiac events, whereas continuation of ACEI or institution of ACEI early after cardiac surgery is associated with improved outcomes.
Perspective:
Use of ACEI in the early perioperative period following CABG has been considered somewhat controversial in the past; the major concern being that ACEI in the setting of CPB may necessitate greater need for pressors and fluid resuscitation support. As a result, withdrawal of ACEI has become common practice at some institutions. While not a randomized study, this large prospective study provides robust data suggesting that continuation of ACEI throughout the entire perioperative period is both safe and has a beneficial effect on cardiovascular, neurological, and other outcomes, and addition of ACEI to patients not already on such is similarly beneficial. Abrupt withdrawal of ACEI prior to cardiovascular surgery resulted in substantially worse outcomes. The mechanism by with ACEI mitigates against a broad range of composite endpoints obviously relates to its blocking of the renin-angiotensin system, which is known to be hyperactive at the time of CPB and likely is a mediator of microvascular events, which is subsequently a presumed course of ischemic, renal, and cerebral events. The significant reduction in a broad range of cardiac events such as reported here attributable to continued or starting of ACEI at the time of CPB CABG should lead to a rethinking of the policy for its withdrawal. It would appear based on this study, that continuation of ACEI throughout the entire perioperative period is both safe and protective against events.
Keywords: Risk, Myocardial Infarction, Stroke, Resuscitation, Brain Diseases, Vasoconstrictor Agents, Renin-Angiotensin System, Creatine, Cardiovascular Diseases, Cardiopulmonary Bypass, Kidney, Cardiac Surgical Procedures, Coronary Artery Bypass, Hypertension, Diabetes Mellitus
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