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ORLANDO -- Beta blocker use starting 2 to 4 hours before noncardiac surgery protected patients against myocardial infarction (MI) but was associated with more death and stroke at 1 year, the POISE (Perioperative Ischemic Evaluation) trialists found, confirming earlier 30-day results.

One year after noncardiac surgery, those randomized to extended-release metoprolol had a 5% rate of MI compared with 6% for those who received placebo (HR 0.78, 95% CI 0.65-0.94). The same 1% incidence of cardiac revascularization in both groups turned out to be an advantage for beta blocker recipients (HR 0.47, 95% CI 0.28-0.78).

All-cause mortality, meanwhile, was elevated in the metoprolol group arm (10% versus 9%, HR 1.16, 95% CI 1.01-1.34), driven by excesses not in cardiovascular but in non-cardiovascular mortality (6% versus 5%, HR 1.22, 95% CI 1.01-1.48). Stroke was also more likely, at 2% versus 1% (HR 1.52, 95% CI 1.09-2.12), reported P.J. Devereaux, MD, PhD, of McMaster University in Hamilton, Ontario, at the American College of Cardiology annual meeting here.

" suggest that at 1 year, for every 1,000 patients having noncardiac surgery, metoprolol would prevent 12 patients from experiencing an MI and six from undergoing cardiac revascularization, but results in excess of 13 deaths and six strokes," Devereaux said.

The thinking was that beta blockers would offset an increase in catecholamine during surgery, thereby decreasing the risk of perioperative MI. Indeed, 30-day outcomes in had shown reduced MI -- but with the tradeoff of more strokes and mortalities.

Now, the same phenomena are visible at 1 year. The independent predictors of 1-year mortality were determined to be as follows:

• MI (OR 3.07, 95% CI 2.39-3.94)
• Coronary revascularization (OR 0.31, 95% CI 0.13-0.76)
• Stroke (OR 5.94, 95% CI 4.16-8.48)
• Cardiac arrest (OR 11.80, 95% CI 6.51-21.3)
• Pulmonary embolism (OR 11.6, 95% CI 5.32-25.20)

For the blinded trial, Devereaux randomized 8,351 patients undergoing noncardiac surgery to beta blockade or placebo. The former received 100 mg of the drug 2-4 hours before surgery and at 6 hours post-operation; starting on post-surgery day 1, the beta blocker group then received 200 mg daily for 30 days, with patients who became hypotensive or bradycardic getting a halved dose.

The beta blocker and placebo groups shared comparable patient characteristics at baseline and in the number of surgeries undertaken.

A total of 191 sites in North America, South America, Europe, Asia, and Australia participated.

Long-term outcomes were gathered through administrative databases in Canada and active follow-up in more than half of the study population in other countries.

In addition to the above-mentioned differences in outcomes between the two groups, the results showed that neither group experienced more cardiac arrests or pulmonary embolisms.

One of the panelists at the session where the study was presented, Kim Eagle, MD, director of the Frankel Cardiovascular Center at the University of Michigan in Ann Arbor, commented that he was uncomfortable with the metoprolol dosing in POISE.

"In retrospect, the dose is too large," Devereaux agreed in response. Another issue, he added, was that the level of hemodynamic monitoring prevented clinicians from identifying patients with hypotension early on. Being slow to respond to this is where clinicians would lose out on the safety of perioperative beta blockers.

There's a lot of work to be done regarding perioperative hemodynamics, Devereaux emphasized. "The OR setting is where things go off the rails."

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