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Perioperative ACE Inhibitors reduce CABG risks

NEW YORK (Reuters Health) – Outcomes of coronary artery bypass graft (CABG) surgeries were improved when patients received angiotensin-converting enzyme inhibitors (ACEIs) perioperatively in a recent study.

The approach is controversial. Perioperative ACEIs have been linked to low systemic vascular resistance and a higher incidence of cardiovascular events after surgery.

The new analysis, published online June 19 in Circulation, is by Dr. Benjamin Drenger of Hadassah-Hebrew University and Dr. Manuel L. Fontes of Duke University and the International Multicenter Study on Perioperative Ischemia-Epidemiology II Research Group.

Altogether the research team had access to prospectively collected data on more than 4,200 patients treated at 72 hospitals in 17 countries.

They excluded patients who died within 48 hours of surgery and stratified their cohort into a continuation group (ACEIs before and after surgery), a withdrawal group (ACEIs preoperatively but not postoperatively), an addition group (ACEIs started only after surgery), and a no-ACEI group.

The four groups were similar demographically and surgically, except that no-ACEI patients had fewer cardiovascular and other co-morbidities and shorter times for cardiopulmonary bypass and cross-clamping.

Compared to patients in the no-ACEI group, patients in the continuation group were 31% less likely to experience congestive heart failure (p=0.05), myocardial infarction (p=0.03), or the composite outcome of death or cardiac, renal, or cerebral adverse events (p=0.009). The no-ACEI patients were only half as likely as the continuation group to need two or more non-routine vasopressors (p = 0.001), however.

Compared to patients in the withdrawal group, patients in the continuation group had significantly lower odds of nearly all the negative outcomes (i.e., death after 48 hours, organ dysfunction, myocardial ischemia/infarction, and the composite endpoint), except for in-hospital deaths and strokes. For those, the rates were similar whether patients stayed on ACEIs or had them withheld after surgery. ACEI withdrawal, however, was associated with significant increases in need for blood transfusions and cardiac assist devices.

The addition group (ACEIs started postoperatively) accounted for only 14.4% of the cohort, but its patients had a 44% lower risk for the composite outcome than patients who didn’t receive ACEIs at all (p=0.004).

“In patients undergoing CABG surgery with cardiopulmonary bypass, continuation of ACEI therapy early after surgery or adding ACEI de novo postoperatively can be associated with marked improvement in cardiovascular and renal outcomes,” the paper concludes. “Conversely, a practice of withdrawing of ACEI treatment postoperatively is associated with poor in-hospital fatal and nonfatal outcomes.”

In an editorial, three cardiac anesthesiologists from Johns Hopkins University in Baltimore, Maryland, expressed some reservations about the observational nature of the study and called for a randomized trial.

A cardiac surgeon who wasn’t involved in the research also had some reservations about the study design. Dr. Dimitri Kalavrouziotis of the Cleveland Clinic told Reuters Health by email, “The issue here is what the authors of the editorial nicely discuss by referring to the fact that patients who are treated with an ACEI are sicker at baseline; therefore, increased inotrope use postop in these patients is not surprising. This is classic confounding by indication. A more valid analysis may have been to look at these outcomes only among patients who were propensity-matched.”

The editorialists also said. “The study is important, however, in that it forces providers to re-examine the practice of routinely discontinuing ACEI perioperatively. Our advice to readers is to be open minded, stay tuned for further outcomes data and accept change as evidence becomes available.”

Dr. Kalavrouziotis agreed, “The authors of the study should be congratulated for their valiant attempt to shed some light on this important question. However, as mentioned in the editorial, causation cannot be established from retrospective data. Stated differently, the factors that cause clinicians to withdraw or to never initiate ACEI are the same factors that are associated with postoperative adverse events. In order to treat a patient with an ACEI postop you need a ‘healthy patient.’ You need a decent blood pressure, normal or near-normal renal function. You need a patient who is extubated and can swallow pills, etc.”

The two lead authors, Dr. Drenger and Dr. Fontes, noted in an email to Reuters Health that while the study was observational, it was at least prospective. And according to their paper, each study center “enrolled patients according to a systematic random sampling scheme.”

“Of course,” they acknowledge, “a formal randomized clinical trial would give stronger statistical results. We believe that those results will not be different from those shown in the current study, which are partially supported by the literature existing today. The ACEIs are generic drugs and it is hard to believe that such a prospective study will ever be performed.”

Dr. Kalavrouziotis said he only prescribes ACEIs to patients with an established indication such as a previous MI, heart failure, diabetes, refractory hypertension, or a depressed cardiac ejection fraction. He does not routinely stop ACEIs preoperatively.

Drs. Drenger and Fontes use similar indications and said, “Our study calls for extra caution in withdrawing ACEI therapy after cardiac surgery.”


Circulation 2012.