Angiotensin-Converting Enzyme Inhibitor Use in Coronary Artery Bypass Graft Surgery
Abstract & Commentary
By Michael H. Crawford, MD, Editor
Source: Drenger B, et al. 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. Circulation 2012;126:261-269.
Angiotensin-converting enzyme inhibitor (ACEI) therapy may be beneficial during coronary artery bypass graft (CABG) surgery because of its anti-inflammatory and other vascular benefits. However, ACEI therapy can cause vasoplegia and acute renal injury, so its use has been controversial. Accordingly, the International Multicenter study on Perioperative Ischemia Epidemiology II Research Group performed a prospective, longitudinal, observational study to characterize perioperative ACEI use in patients undergoing CABG and determine its relationship to in-hospital cardiovascular events. The primary outcome of the study was a composite of cardiac, cerebral and renal events, and mortality. Of the 5436 patients enrolled from 72 centers in 17 countries, 371 were excluded for procedural reasons and an additional 841 were excluded because they did not meet inclusion criteria (e.g., some had concomitant valve surgery). Of the 4223 remaining, 1838 were treated preoperatively with ACEI and 2386 were not treated, by physician discretion. After surgery, the patients segmented into four groups: 1) those continuing on ACEI, 2) those withdrawn from ACEI, 3) those in whom ACEI was added, and 4) those never on ACEI. Non-fatal events were significantly reduced in those continuing on ACEI therapy vs the never on ACEI group (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.52-0.91; P = 0.009), as were cardiovascular events (OR, 0.64; CI, 0.46-0.88; P = 0.006). Similar results were seen in comparing those started on ACEI therapy postoperatively vs the never on ACEI group. Continuous ACEI vs withdrawal of ACEI decreased total events, cardiovascular events, and renal events (P = 0.005). Mortality and cerebral events were not different in the four groups. The authors concluded that no ACEI therapy or withdrawal of ACEI is associated with non-fatal cardiovascular and renal events.
It is a common practice to withdraw ACEI therapy prior to CABG and not restart it in the hospital. In this observational, multicenter study, withdrawal was done in 50% of cases. When the Kaplan-Meier event-free survival curves of the four groups were inspected, it was clear that the withdrawal group did the worst. Continuing ACEI therapy reduced adverse events by 50%, whereas withdrawing ACEIs increased renal events by 113%. The other three groups’ results are more similar. Interestingly, if you compare the two larger groups of those on ACEI therapy preoperatively to those who were not, these two groups have significant differences in clinical characteristics. Those on ACEI therapy had higher incidences of heart failure, myocardial infarction, stroke, diabetes, and renal disease.
In this study, the continuing ACEI group did require more vasopressor support, which is consistent with earlier reports that led to the practice of withdrawing ACEIs before CABG. However, as discussed above, these were higher risk patients with more comorbidities, which can also explain the vasopressor needs. Despite the need for vasopressors, there was no difference in postoperative blood pressure, cardiac output, or time to extubation in the four groups.
Experimental studies have shown that cardiopulmonary bypass activates the renal angiotensin aldosterone system, which can have deleterious vascular effects beyond an increase in blood pressure. Thus, the authors believe that their observational study compels us to continue or start ACEI therapy pre- and post-operatively in CABG patients. However, observational studies have biases and confounders that cannot be fully adjusted and so are only hypothesis generating. If you look only at those on ACEI therapy, clearly the events increased when ACEIs were withdrawn. Thus, my take is that this is a poor practice and should be discouraged. However, until a randomized, controlled trial is done, I am not willing to push for the addition of ACEI therapy in patients with no indications for it.