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ACE Inhibitors and CABG Outcomes
Abstract & Commentary
By Michael H. Crawford, MD
Sources: Miceli A, et al. Effects of angiotensin-converting enzyme inhibitor therapy on clinical outcomes in patients undergoing coronary artery bypass grafting. J Am Coll Cardiol. 2009;54:1778-1784. Bach DS. Angiotensin-converting enzyme inhibitor therapy at the time of coronary artery bypass surgery. J Am Coll Cardiol. 2009;54:1785-1786.
The preoperative use of angiotensin-converting enzyme inhibitors (ACEI) with coronary artery bypass graft (CABG) surgery is controversial. Thus, these investigators from the United Kingdom performed a retrospective, observational study of patients undergoing isolated CABG who did not have cardiogenic shock. The final population included over 9,000 patients, 51% of whom received preoperative ACEI. To avoid bias, a propensity score matched analysis was done on 3,052 patients on ACEI and a control group of equal number. The primary endpoint was in-hospital mortality. In the original group, there were many significantly different clinical variables between the ACEI and the non-ACEI groups, as you would expect, but the smaller matched groups were similar on all these measures.
Results: Overall mortality was 1%, and preoperative ACEI doubled this risk (1.3% vs. 0.7%, OR 2.0, CI 1.17-3.42, p = 0.013). Also, renal dysfunction, atrial fibrillation, and use of inotropic support were more common in the ACEI group. There was no difference in myocardial infarction and stroke. The authors concluded that preoperative ACEI use was associated with increased mortality, renal dysfunction, atrial fibrillation, and use of inotropic support in CABG patients.
The controversy over ACEI use preoperatively with CABG surgery concerns two viewpoints: pro, ACEI lower blood pressure and are vasculoprotective, anti-inflammatory, and anti atherosclerotic; con, ACEI cause vasodilation and an increased need for fluids, inotropic agents, and vasoconstrictors. The data from the study support the latter. It is well known that hypotension causes renal dysfunction, yet ACEI are recommended for diabetics to prevent deterioration in renal function. Clearly, there is a difference between preoperative use and chronic use in ambulatory patients with coronary artery disease (CAD). The lack of effect on atrial fibrillation is disappointing since this is a common complication of CABG that increases adverse events and prolongs hospital stay. Theoretically, an ACEI should reduce atrial pressure and volume and the stimulus for atrial fibrillation, but this was not observed. Should we hold ACEI for patients undergoing CABG?
Before we decide, it is worth noting that this study has several limitations. Although theoretically attractive, propensity score matching may not eliminate all bias from non-randomized studies, and there were considerable differences between those on and not on ACEI before matching, as you can imagine. Also, ACEI may not be the culprit, but rather a marker for some adverse patient characteristic that was not measurable. If you want to apply the results of the study, there are important details missing from this report. What was the duration of ACEI therapy; the dose; the agent? What about angiotensin receptor blockers and aldosterone antagonists? If you hold ACEI preoperatively, when can you restart?
In the accompanying editorial, Dr. Bach describes ACEI as one of the four pharmacologic pillars of secondary prevention in CAD, along with aspirin, beta blockers, and statins. However, all four drugs may not be appropriate for all patients. One should consider the risk vs. benefit of each. Today, hospitals and practitioners are rated on how many of their patients are on these drugs at admission and at discharge. This tends to drive formulaic, algorithm-driven medicine, which may not always be appropriate. Recently, our percentage of patients with left ventricular dysfunction discharged on ACEI dropped from 100% to below targets. Hospital administrators wondered what happened. It turned out that the drop was due to patients post-CABG. Clearly, our surgeons had gotten wind of this controversy and voted with their pens. We are trying to get them to re-institute ACEI therapy before the patient leaves the hospital, but it is an uphill battle. More data, especially randomized, prospective data, would be welcome on this controversial topic.