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Perioperative β-Blockers: Fewer MIs but Increased Mortality

A landmark trial casts doubts on the liberal use of β-blockers perioperatively.

In several small trials published in the late 1990s, perioperative β-blockade reduced the incidence of cardiac ischemic complications associated with noncardiac surgery. However, two medium-sized trials published in 2006 failed to duplicate the previous findings (JW Nov 29 2006). This uncertainty set the stage for the large POISE trial, conducted in 23 countries.

All 8351 enrolled patients (age 45) were scheduled for noncardiac surgery and met at least one of the following criteria: history of coronary disease, stroke, or peripheral vascular disease; recent hospitalization for heart failure; undergoing major vascular surgery; or any three of seven other risk criteria outlined in the protocol. Patients were randomized to receive extended-release metoprolol (100 mg) or placebo 2 to 4 hours before surgery. Postoperatively, patients received metoprolol (maximal dose, 200 mg daily) or placebo for 30 days, titrated according to blood pressure and pulse parameters.

At 30 days, the incidence of the primary composite endpoint (cardiovascular death, nonfatal myocardial infarction, or nonfatal cardiac arrest) was lower with metoprolol than with placebo (5.8% vs. 6.9%; P=0.04). This difference was driven by a significantly lower incidence of nonfatal MI in the metoprolol group (3.6% vs. 5.1%; P=0.001). However, overall mortality was higher in the metoprolol group than in the placebo group (3.1% vs. 2.3%, P=0.03), as was stroke incidence (1.0% vs. 0.5%; P=0.005). Clinically important hypotension and bradycardia occurred significantly more often with metoprolol than with placebo, and post hoc multivariable analysis suggested that hypotension partly explained the link between metoprolol and mortality and metoprolol and stroke. Additional analyses did not identify any subgroup that benefited from metoprolol.

Comment: This landmark trial calls into question the liberal use of perioperative β-blockers advocated by some authorities. Although different β-blockers or different dosing strategies could conceivably have produced different outcomes, for now β-blockers should not be initiated perioperatively in patients who are similar to those in this trial. However, clinicians should continue β-blockers perioperatively in patients who already receive them for valid clinical indications. In addition, if preoperative evaluation identifies a patient who should be taking a β-blocker but is not (e.g., someone with recently symptomatic ischemic heart disease), the drug should be started and titrated on an outpatient basis, if possible.

— Allan S. Brett, MD

Published in Journal Watch General Medicine May 22, 2008

Citation(s):

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 ahead of print].(http://dx.doi.org/10.1016/S0140-6736(08)60601-7)