AHA: Surgery with Beta-Blockers Onboard May Be Risky


ORLANDO, Nov. 7 -- Beta-blockers given before noncardiac surgery to prevent cardiovascular events in at-risk patients may be counterproductive, researchers found.
Action Points
Caution interested patients that although the study did not support the use of beta-blockade for prevention of perioperative events, it did not suggest that patients should stop taking the drug prescribed for other indications.
Note that this study was published as an abstract and presented orally at a conference. The data and conclusions should be considered to be preliminary until published in a peer-reviewed publication.
Perioperative metoprolol (Lopressor, Toprol-XL) started two to four hours before surgery prevented 15 MIs, three revascularizations, and seven atrial fibrillation events per 1,000 treated patients compared with placebo, according to a large prospective trial presented here at the American Heart Association meeting.
But this came at the expense of eight deaths, five severe strokes, 42 cases of significant bradycardia, and 53 significant hypotension events per 1,000 patients, reported P.J. Devereaux, M.D., of McMaster University in Hamilton, Ontario, and colleagues.
The "disturbing" increase in death and stroke recommends against routine use, commented Gordon F. Tomaselli, M.D., of Johns Hopkins University, who moderated a press conference at which the results were presented.
However, the drug should not be withdrawn for patients who come in for surgery and are already on beta-blockers for other indications, Dr. Tomaselli cautioned. "That's absolutely the wrong thing to do."
Perioperative beta-blockade for noncardiac surgery is a quality-of-care measure of the Physicians Consortium for Performance Improvement and the Surgical Care Project.
Likewise, joint guidelines from the AHA and the American College of Cardiology recommend perioperative beta-blockers for patients with heart disease or with risk factors, and suggest use can be considered for patients with low or intermediate risk as well. Neither recommendation had better than a moderate level of evidence.
"There's an enormous push to do this based on small trials," Dr. Devereaux said, which he compared to the situation that existed with hormone replacement therapy before the Women's Health Initiative linked it to breast cancer risk.
However, even the small trials have not consistently found a benefit.
So, Dr. Devereaux's group conducted the large Perioperative Ischemic Evaluation (POISE) trial. It included 8,351 patients 45 or older who were undergoing noncardiac surgery and had or were at risk for atherosclerotic disease.
Patients were randomized to receive a continuous-release formulation of metoprolol or placebo starting two to four hours before surgery and continuing for 30 days afterward.
Overall, 82% of patients had evidence of coronary artery or peripheral vascular disease before surgery. Treatment groups were balanced in risk factors and type of surgery.
Metoprolol reduced risk of the primary composite endpoint of cardiovascular death, nonfatal MI, and nonfatal cardiac arrest at 30 days compared with placebo (5.8% versus 6.9%, hazard ratio: 0.83, P=0.04).
This benefit was driven by a decrease in nonfatal MI (3.6% versus 5.1%, HR: 0.70, P=0.0007), which, although important, is typically less important to patients than risk of stroke, Dr. Devereaux said.
Stroke was more common after surgery among patients who received beta-blockers (1% versus 0.5%, HR: 2.17, P=0.005). And, total mortality was elevated with metoprolol compared with placebo (3.1% versus 2.3%, HR: 1.33, P=0.03).
Dr. Devereaux noted that these were not "benign strokes" and may have been caused by increases in other secondary outcomes, particularly hypotension and atrial fibrillation.
Among the other secondary findings, rates for metoprolol compared with placebo included:
Elevated for clinically significant hypotension (15% versus 9.7%, HR: 1.55, P0.0001).
Elevated for clinically significant bradycardia (6.6% versus 2.4%, HR: 2.71, P0.0001).
Reduced for atrial fibrillation (2.2% versus 2.9%, HR 0.76, P=0.04).
Slightly reduced for revascularization (0.3% versus 0.6%, HR: 0.41, P=0.01).
These findings were disappointing and leave surgeons with few options for prevention of ischemic events, Dr. Devereaux said.
"One of the reasons beta-blockers were pushed despite weak evidence is that we have nothing than we know works," he said.
Rather than studying other similar drugs for perioperative prevention, Dr. Devereaux suggested that the best strategy might simply be better monitoring after surgery to quickly identify and treat any events that do occur.
Nevertheless, the decision on whether to use perioperative beta-blockade will need to be decided with patients individually, he concluded.
The study was funded by AstraZeneca and national granting agencies in several countries.
The researchers made no declarations regarding financial conflicts of interest. Dr. Tomaselli reported no conflicts of interest.
Primary source: American Heart Association meetingSource reference: Devereaux PJ, et al "The Perioperative Ischemic Evaluation (POISE) Trial: A Randomized Controlled Trial of Metoprolol versus Placebo in Patients Undergoing Noncardiac Surgery" AHA meeting 2007; Abstract LBCT-20825.