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Perioperative Beta Blockers
Abstract & Commentary
By Michael H. Crawford, MD, Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco. Dr. Crawford serves on the speaker's bureau for Pfizer. This article originally appeared in the February 2009 issue of Clinical Cardiology Alert. It was peer reviewed by Rakesh Mishra, MD. Dr. Mishra is Assistant Professor of Medicine, Weill Medical College, Cornell University. He reports no financial relationships relevant to this field of study.
Source: Bangalore S, et al. Perioperative beta blockers in patients having non-cardiac surgery: a meta-analysis. Lancet. 2008;372:1962-1976.
The ACC/AHA guidelines recommend perioperative beta blockers for those already on them, patients undergoing vascular surgery, or those having intermediate- to high-risk surgery with established coronary heart disease, or at high risk of having it. However, recent studies have shown no beneficial effect of perioperative beta blockers and potential for harm. Thus, Bangalore et al conducted a meta-analysis of randomized, controlled trials of safety and efficacy outcomes of perioperative beta blockers assessed for 30 days post-non-cardiac surgery. The efficacy outcomes of interest were total mortality, cardiovascular mortality, myocardial infarction, stroke, and heart failure. The safety outcomes of interest were bronchospasm, bradycardia, and hypotension. The selection criteria were met by 33 trials out of 112 surveyed, and included over 12,000 patients. Beta-blocker therapy did not result in any significant reduction in total mortality, cardiovascular mortality, or heart failure, but did reduce myocardial infarction (OR = 0.65, 95% CI 0.54-0.79, NNT = 63). However, stroke was increased (OR = 2.0, 1.27-3.68, NNH = 293), as was bradycardia (NNH = 22) and hypotension, requiring therapy (NNH = 17); bronchospasm was not affected. An assessment of the trial methodology showed that only 13 had a low risk of bias. The beneficial results for myocardial infarction were driven by the 20 trials with a high risk of bias. Bangalore et al concluded that randomized trial data do not support the use of beta blockers preoperatively to prevent cardiovascular events in non-cardiac surgery patients.
Although I am not a big fan of meta-analyses, this one was very carefully done and raises some interesting points. First, it exhibits how few excellent trials on this topic exist. Out of 112 reports of randomized, controlled trials of perioperative beta-blocker use with 30-day outcome data, only 33 met their quality inclusion criteria. Of those, only 13 were considered low risk for bias. The large, positive trial of Poldermans et al,1 published in the New England Journal of Medicine, drove the positive data about outcomes with beta blockers, but was considered highly biased by Bangalore et al because many of the high-risk patients they studied should have been on beta blockers for other indications (eg, heart failure, post myocardial infarction); in the Poldermans study, myocardial infarction decreased 44%. Second, much of the negative data on beta blockers were driven by the POISE study,2 which was considered low risk for bias. If POISE is eliminated, the reduction in myocardial infarction increases from 35% to 53% with beta blockers. Bangalore et al correctly point out that the doses of beta blockers used in POISE was eight times the equivalent dose of the agent used in the Poldermans study. Thus, some of the negative effects in POISE may have been due to giving such a large dose of beta blockers to beta-blocker naive patients. Third, sensitivity analyses showed that outcomes were better if beta blockers were titrated to a heart rate of < 75 beats/min and if they were administered for 24 hours or less. The latter is interesting since the largest percentage of perioperative events are thought to occur 48-120 hours after surgery.
So what do we do with this new data? It seems clear that if your patient is already on beta blockers for clear indication, he/she should stay on them. Those who should be on beta blockers for other reasons should be started on them early enough to titrate the dose to appropriate levels prior to surgery. All others should be considered on a case-by-case basis. For example, someone with known coronary artery disease, or who is highly likely to have it, and is undergoing high-risk surgery, may be an acceptable candidate, if he/she seems able to tolerate beta blockers. It is always ideal to have a few weeks to start therapy. The higher risk of beta-blocker complications in POISE was associated with the administration of high doses without titration just before surgery. This is probably not a good idea. Also, I agree with Bangalore et al that perioperative beta blockers should not be a practitioner performance measure until the issue is clarified further.
1. Poldermans D, et al. The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. N Engl J Med. 1999;341:1789-1794.
2. POISE study group. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008;371:1839-1847.