Author(s): Bangalore S, Wetterslev J, Pranesh S, Sawhney S, Gluud C, Messerli FH.
Citation: Lancet 2008;Nov 12:[Epub ahead of print].
Clinical Trial: No
Study Question: What is the published evidence regarding perioperative β-blockers in patients undergoing noncardiac surgery?
Methods: The authors performed a meta-analysis of randomized controlled trials of β-blocker use in noncardiac surgery. The endpoints of interest were 30-day all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, and heart failure. The authors followed the recommendations from the Cochrane Collaboration and the Quality of Reporting of Meta-analyses guidelines.
Results: The authors included 33 trials with 12,306 subjects. Taken together, these trials suggested no effect of β-blockers on all-cause mortality, cardiovascular mortality, or heart failure, but β-blockers were associated with a decrease (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.54-0.79) in nonfatal myocardial infarction (number needed to treat [NNT] 63) and decrease (OR, 0.36; CI, 0.26-0.50) in myocardial ischemia (NNT 16). However, β-blockers were associated with an increase (OR, 2.01; CI, 1.27-3.68) in nonfatal strokes (number needed to harm 293). Sensitivity analysis suggested that increased risk of stroke was driven by the very large POISE trial, but that the decrease in nonfatal MI and myocardial ischemia were not. Sensitivity analysis also suggested that in patients undergoing high-risk surgery, those receiving β-blockers had decreased all-cause mortality (OR, 0.37; CI, 0.18-0.77).
Conclusions: The authors concluded that the evidence does not support the use of β-blockers for the prevention of perioperative clinical outcomes in patients having noncardiac surgery. They also opine that the American College of Cardiology/American Heart Association (ACC/AHA) should soften their advocacy for this intervention until conclusive evidence is available.
Perspective: This meta-analysis has two sources of bias not addressed by the authors. One is that these 33 trials used markedly different β-blocker regimens, and markedly different patient populations. This makes it very difficult to make a blanket statement about β-blocker therapy. Second, a single study contributed 68% of the subjects in this meta-analysis, possibly skewing the results, as their sensitivity analysis suggests. That one study, POISE, used a regimen of metoprolol CR 200 mg daily without a run-in phase to assure appropriateness or tolerance of therapy. Finally, the authors’ conclusions greatly oversimplify their observations. (The ACC/AHA guidelines do not advocate β-blocker therapy, but rather advocate very selective, tailored β-blocker therapy in a small subset of highest risk patients undergoing high-risk surgery.) This meta-analysis includes trials of widely varying—sometimes high-dose—β-blocker regimens in a wide range of patients, many of whom are low-risk undergoing low-risk surgery. Unfortunately, this meta-analysis therefore merely summarizes the fact that much remains to be learned about the appropriate use of perioperative β-blocker therapy. The authors’ sweeping conclusions oversimplify the data and the discussion. James B. Froehlich, M.D., F.A.C.C.
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