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In the 1990s, several small trials (with ≤200 subjects) suggested that β-blockers lowered risks for perioperative adverse cardiovascular events in high-risk patients who undergo noncardiac surgery. These findings resulted in expanded use of perioperative β-blockers, but some experts called for more robust evidence to support this practice. Thus, a research team led by Canadian investigators organized a large international randomized trial called POISE (PeriOperative ISchemic Evaluation Study); the trial’s results were published in 2008 (JW May 22 2008).
Researchers enrolled more than 8000 patients who were scheduled for noncardiac surgery and had risk factors for perioperative cardiovascular complications. Patients received extended-release metoprolol (100 mg) or placebo, starting 2 to 4 hours before surgery and continuing for 1 month postoperatively. Although the 30-day incidence of nonfatal myocardial infarction was significantly lower in the metoprolol group than in the placebo group (3.6% vs. 5.1%), the metoprolol group experienced significantly higher all-cause mortality (3.1% vs. 2.3%) and a significantly higher incidence of stroke (1.0% vs. 0.5%). In part, these adverse outcomes were mediated by higher rates of hypotension and bradycardia with metoprolol than with placebo. No subgroup clearly benefited from metoprolol.
This landmark trial has muddied the waters regarding perioperative β-blockade. The investigators and their supporters argue that the harms of perioperative β-blockade likely outweigh the lower risk for nonfatal MI. In contrast, critics of POISE claim that the dose of metoprolol was too high or that β-blockers should have been started well in advance of surgery and not immediately preoperatively.
In my view, initiation of β-blockers during the hours before noncardiac surgery in clinically stable β-blocker–naive patients should be abandoned on the basis of POISE. Although cardioselective β-blockers — started weeks before noncardiac surgery and titrated to specified blood pressures and pulse ranges — conceivably benefit certain high-risk patients, the precise identity of that subgroup remains elusive. However, experts generally recommend that patients who are already receiving long-term β-blocker therapy for valid indications should continue taking these drugs perioperatively.