For patients at elevated cardiac risk who are undergoing major noncardiac surgery, early perioperative use of beta-blockers is associated with significantly lower 30-day all-cause mortality and cardiac morbidity, according to a report in the April 24 issue of JAMA.
In a retrospective cohort study, this association was strongest in the patients at highest cardiac risk – those with two or more factors on the six-item Cardiac Risk Index, said Dr. Martin J. London of the department of anesthesia and perioperative care, U.S. Department of Veterans Affairs Medical Center, San Francisco, and his associates.
Dr. Martin London
Beta-blocker use in this setting remains controversial, and the use of perioperative beta-blockers has been declining, because of safety concerns. To examine whether high-risk patients are helped or harmed by the treatment, Dr. London and his colleagues analyzed data from the VA Surgical Quality Improvement Program database, a VA pharmacy database, and a VA administrative database.
They assessed the records of 136,745 patients who had vascular, general, neurologic, orthopedic, thoracic, urologic, or otolaryngologic surgery at 104 VA medical centers in 2005-2010.
A total of 40.3% of these subjects had received beta-blockers on the day of or the day after surgery, and 33.2% were given outpatient prescriptions for beta-blockers within 7 days of surgery.
There was a modest but significant decline in beta-blocker use during the 5-year study period, from 43.5% in the first year to 36.2% in the last. A similar national trend has been reported in previous studies. "This may be related to the findings of the POISE trial of increased stroke and death in treated patients, leading to more conservative guideline recommendations within this period," the investigators said.
They performed 1:1 propensity matching and identified 37,805 matched pairs of exposed and nonexposed patients for the primary outcome analysis. The primary outcome measure – all-cause mortality at 30 days – was significantly lower (relative risk 0.73) among patients who used beta-blockers than among those who did not, with a number needed to treat of 241 (JAMA 2013;309:1704-13).
The study subjects were categorized according to their scores on the revised Cardiac Risk Index, which includes six variables: high-risk surgery, cerebrovascular disease, ischemic heart disease, heart failure, diabetes, and renal insufficiency. Patients who had two or more of these CRI risk factors showed the greatest mortality benefit from perioperative beta-blocker therapy, with an relative risk of 0.63.
When the data were broken down by type of surgery, mortality remained significantly lower in beta-blocker users, compared with nonusers for every category except vascular surgery. In previous studies, beta-blockers have shown equivocal benefit in this same subgroup of surgery patients, Dr. London and his associates noted.
The secondary outcome measure of the study was a composite of Q-wave myocardial infarction or nonfatal cardiac arrest at 30 days. These may be rare complications but they are highly predictive of subsequent mortality, the researchers said.
Again, patients who took beta-blockers showed significantly less cardiac morbidity than those who did not, with a relative risk of 0.67 and a number needed to treat of 339.
The study results remained robust in a sensitivity analysis that categorized patients according to whether they had been taking beta-blockers before hospitalization, as well as in a sensitivity analysis that categorized patients as either acute or chronic users of beta-blockers.
This study confirmed the previous finding that withdrawal of beta-blockers within 30 days of surgery is associated with increased mortality. In this study, the risk of death was approximately doubled if beta-blockers were withdrawn perioperatively.
In a post hoc analysis, "we were unable to demonstrate significant associations of perioperative beta-blockade with the risk of postoperative stroke." There was no significant difference in stroke rates between patients who received beta-blockers and those who did not, Dr. London and his colleagues said.
This study was supported by a grant from the Anesthesia Patient Safety Foundation. Dr. London reported no financial conflicts of interest. An associate reported ties to Roche, Resverlogie, Anthera, and Sanofi.