More calls to take gamma knife to beta-blockade recommendation

Guidelines should retract recommendations to perioperatively initiate beta-blockers in noncardiac surgery patients who are at risk of cardiac events, the authors of a meta-analysis proposed. Their study found the practice increased the risk of postoperative death.

The results, published online July 31 in Heart, contradict findings from the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) trials, which have been cited by the American College of Cardiology, the American Heart Association and the European Society of Cardiology as evidence in setting guidelines.

In 2008, a review published in The Lancet challenged guidelines after finding the “beneficial effects [of beta-blockers] were driven mainly by trials with a high risk of bias.” The lead researcher, Donald Poldermans, MD, PhD, later was dismissed from Erasmus Medical Center in Rotterdam, the Netherlands, for violations including the use of fictitious and unreliable data.

Sonia Bouri, MD, of St. Mary’s Hospital in London, and colleagues revisited the issue with a meta-analysis of 11 randomized controlled clinical trials that compared an initiation of beta-blockers preoperatively with placebo in patients undergoing noncardiac surgery. They used Medline, the Cochrane Central Registry of Randomized Trials and other databases to identify trials. Two of the 11 trials were from the DECREASE series of studies.

The primary endpoint in the meta-analysis was all-cause mortality from randomization at 30 days or hospital discharge. Secondary endpoints included nonfatal MI, stroke and hypotension.

In nine studies, they found a statistically and clinically significant 27 percent increase in 30-day all-cause mortality risk with beta-blocker therapy compared with placebo. A separate analysis of the two DECREASE studies found a nonstatistically significant 58 percent decrease in risk.

Both DECREASE and trials with secondary endpoint data showed a reduction in nonfatal MIs and an increase in stroke. Six trials, none from DECREASE, with hypotension data found hypotension in 15.2 percent of patients in the beta-blocker therapy groups vs. 10 percent in control groups.

“Although β-blockers reduce non-fatal MI, they also increase hypotension and stroke,” Bouri et al wrote. “It is conceivable that an increase in death due to hypotension or stroke was overcoming a reduction in death from MI, leaving a net increase in deaths. However, there are insufficient quantitative data on the subclasses of death to be certain: deaths are relatively few and difficult to classify reliably by cause.”

The meta-analysis may have missed unreported trials, and was influenced by POISE, a large, double-blind randomized trial.

Bouri et al concluded that guidelines should not recommend the routine initiation of beta-blockers in patients at risk of cardiac events who undergo high- or intermediate-risk vascular surgery or other surgeries.  “Patient safety being paramount, guidelines for perioperative β-blocker initiation should be retracted without further delay.”