Postsurgical death, stroke increased in patients treated with perioperative beta blockers

After 30-day treatment with metoprolol, patients with or at risk for heart disease were less likely to suffer a myocardial infarction (MI), but more likely to have a stroke or die in the 12 months after noncardiac surgery, according to results from the POISE Trial presented at the American College of Cardiology’s 67 Annual Scientific Session, held from March 10-12 in Orlando, FL.

"Our results suggest at 1 year, for every 1,000 patients having noncardiac surgery, treatment with metoprolol would prevent heart attacks in 12 patients but would result in an excess of 13 deaths and 6 strokes," said lead author P.J. Devereaux, MD, PhD, director of cardiology, McMaster University, Hamilton, Canada.

"While there is little doubt that some patients benefit from receiving beta blockers during the period immediately before and after noncardiac surgery, these data show that at least as many patients are seriously harmed,” he added. “These data tell us that we need to exercise caution when using beta blockers in this setting until we figure out how to mitigate the substantial risks and enable all patients to obtain the potential benefits of this intervention."

Researchers of the PeriOperative Ischemic Evaluation (POISE) Trial, a 23-country randomized, controlled, blinded trial of metoprolol continuous release compared with placebo, previously demonstrated that perioperative beta-blockade could reduce the 30-day risk of MI, while increasing the risk for mortality and stroke in patients undergoing noncardiac surgery. In this study, Dr. Devereaux and his fellow researchers sought to assess the long-term impact of perioperative beta-blockade using 1-year outcomes data from the POISE Trial.

Data were available from 8,351 patients (median age: 69 years; 63% male) undergoing noncardiac surgery who were at risk for perioperative cardiovascular events. All patients were age 45 years or older, with a history of heart or vascular disease, stroke, congestive heart failure, and other comorbid conditions such as diabetes or impaired kidney function.

Patients received metoprolol (200 mg/d) 2 to 4 hours preoperatively, and then for 30 days thereafter or placebo.

At the 1-year follow up, 9.8% and 8.5% of the metoprolol and placebo patients, respectively, had died (metoprolol HR: 1.16; 95% CI: 1.01-1.34; P=0.036).

Metoprolol reduced the risk of MI compared with placebo (5.0% vs 6.2%, respectively; HR: 0.78; 95% CI: 0.65-0.94; P=0.008), as well as the risk for cardiac revascularization (0.5% vs 1.1%: RR: 0.47p 95% CI: 0.28-0.78; P=0.004). The incidence of stroke, however, was higher in the patients treated with metoprolol compared with placebo (2.0% vs 1.4%; HR: 1.52; 95% CI: 1.0-2.12; P=0.014).

Previous results at 30-day follow-up were similar, with less MI in the patients treated with metoprolol compared with placebo (4.2% vs 5.7%, respectively), but more deaths (3.1% vs 2.3%) and strokes (1% vs 0.5%).

Dangerous combination

Postoperatively, many patients undergoing major noncardiac surgery, including hip replacement, knee replacement, bowel resection, or repair of an abdominal aortic aneurysm, are treated with opioids for pain relief. These may mask sharp declines in both blood pressure and/or heart rate, which can be caused by bleeding, heart failure, or sepsis. The combination of such drops with beta blockade can be dangerous.

"Low blood pressure, or hypotension, is common in this setting and is a main contributor to the adverse effects resulting from perioperative beta blockers," said Dr. Devereaux.

Perhaps the metoprolol dose used here was too high, as some observers have suggested. According to Dr. Deveraux, a lower dose may not have been as effective in reducing MI.

"I believe the answer is more continuous patient monitoring during the immediate postsurgical period so that dangerous drops in heart rate or blood pressure are promptly identified and treated," he noted.

Dr. Devereaux and fellow researchers are now conducting a study of the effectiveness of remote, automated patient monitors in reducing such postsurgical cardiac complications.

This study was funded by the Canadian Institutes of Health Research.