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Studies of the benefits of using preoperative beta-blockers to reduce the risk for cardiovascular events in patients undergoing noncardiac surgery have yielded inconsistent results. To investigate this issue further, the Perioperative Ischemic Evaluation (POISE) investigators randomized 8351 patients with cardiovascular disease or at high risk for cardiovascular events (mean age, 69; 37% women) to oral extended-release metoprolol (100 mg) or matching placebo, administered 2 to 4 hours before noncardiac surgery and continued (metoprolol dose, 200 mg/day) for 30 days. The prespecified primary outcome at 30 days after randomization was a composite of cardiovascular death, nonfatal MI, and nonfatal cardiac arrest.
The primary outcome occurred in 5.8% of patients in the metoprolol group and in 6.9% of those in the placebo group (hazard ratio, 0.84; P=0.04). By contrast, more deaths and more strokes occurred in the metoprolol group than in the placebo group (all-cause mortality, 3.1% vs. 2.3%, P=0.032; stroke rate, 1.0% vs. 0.5%, P=0.005). The between-group mortality difference appears to have resulted from higher rates of hypotension, bradycardia, and stroke in the metoprolol group than in the placebo group.
POISE Study Group. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): A randomised controlled trial. Lancet 2008 May 13; [e-pub before print] (http://dx.doi.org/10.1016/S0140-6736(08)60601-7).
Fleisher LA and Poldermans D. Perioperative β blockade: Where do we go from here? Lancet 2008 May 13; [e-pub before print] (http://dx.doi.org/10.1016/S0140-6736(08)60662-5).
Comment
These findings will dampen the current enthusiasm for preoperative use of beta-blockers to reduce cardiovascular risk in patients undergoing noncardiac surgery. In their discussion, the authors estimated that for every 1000 patients with similar risk profiles, extended-release metoprolol prevents 15 MIs but produces eight additional deaths and five additional strokes. The dose of the study medication was relatively high, and the authors of an accompanying editorial speculate that this may have accounted for some of the adverse affects, but we do not know whether a lower dose would have resulted in a more favorable risk-benefit profile. Until results of further research show otherwise, the balance of risks and benefits does not favor this strategy in this patient population.