Beta-blockade boosts noncardiac-surgery outcomes in high-risk patients

Marlene Busko

April 25, 2013

San Francisco, CA - Amid controversy surrounding the use of beta-blockers for noncardiac surgery, a large observational study finds that higher-risk patients who received the drugs on the day of or following nonvascular surgery showed improved 30-day mortality and cardiac morbidity outcomes[1].

The study, by Dr Martin J London (San Francisco VA Medical Center, CA) et al, which experts say will be considered in new guidelines expected in 2014, is published in the April 17, 2013 issue of the J ournal of the A merican M edical A ssociation . Still, they and the authors agree that it is hypothesis-generating rather than definitive.

"I believe that this paper confirms some of the [American Heart Association] AHA guideline recommendations that it is a good idea to continue the beta-blocker in patients who are already taking them [at noncardiac surgery]," London told heart wire . And, he said, "it probably confirms some of [the work of Dr Don Poldermans (Erasmus Medical Center, the Netherlands), suggesting] that there are probably patients who might benefit from being started on beta-blockers, who are at higher risk."

But because it presents only observational data, he said, it should serve only to help in the design of "a well-conducted randomized trial in these types of patients."

Dr Sidney C Smith (University of North Carolina, Chapel Hill) agreed. "I think this is a well-conducted trial by careful investigators who do a good job in pointing out its limitations." Further, he said, it presents a number of hypothesis-generating questions that merit consideration in a prospective randomized controlled trial. "The two things that stand out here are the differences from the POISE stroke data and the observations about met oprolol vs at enolol, in terms of better outcomes with atenolol." Whereas the POISE trial saw an excess of strokes in patients given beta-blockers, strokes were not increased in the current trial.

Starting beta-blockade remains controversial

The 2009 AHA/ACCF updated guidelines recommended continuing beta-blockers in patients scheduled for noncardiac surgery based on class-1 evidence, but they found no strong evidence for starting beta-blockade.

"After the initial enthusiasm with beta-blockers, people were very confused," London said. "The whole area became quite polarized—Dr Poldermans saying that they're great, other people saying that they're harmful. The POISE study was severely criticized because it was felt that the dose that they gave was quite high."

London and colleagues studied a cohort of 136 745 patients treated at 104 Veterans Affairs medical centers from 2005 to 2010 to explore how perioperative beta-blockade may be associated with outcomes in patients undergoing major noncardiac surgery.

They obtained 37 805 propensity-matched pairs of a patient who was exposed to a beta-blocker and another who was not exposed. Patients were classified according to their number of revised Cardiac Risk Index variables, which included high-risk surgery, cerebrovascular disease, ischemic heart disease, congestive heart failure, diabetes mellitus, and renal insufficiency.

Nonvascular surgery, two or more risk factors

They found a statistically significant 27% reduction in 30-day mortality, the primary outcome, as well as a 33% reduction in nonfatal Q-wave MI or cardiac arrest at 30 days, the secondary outcome (p for both <0.001) associated with beta-blockade. The benefits were concentrated among patients who had two or more risk factors.

Patients with two risk factors who received perioperative beta-blockers had a 37% lower risk of 30-day mortality (compared with matched patients who did not receive a beta-blockade); this decrease in risk was 46% for patients with three risk factors and 60% for patients with four or more risk factors (p for all <0.001).

During the five-year study period, the rate of perioperative beta-blocker use declined significantly, from 43.5% to 36.2%, which "suggests that clinicians are appropriately concerned about the lack of recommendations," London said. The recent scandal surrounding missing data in the DECREASE studies, which led to the firing of Poldermans, has further muddied the waters.

Lack of specific information to guide practice

Smith pointed out that the study was based on data from VA medical centers, [where] "more than 95% of the patients are men, so we don't get any insight into what might be happening in women."

He added, "The apparent benefit of atenolol is something that clearly needs further study, [since] today, most of the guidelines for heart failure and ischemic heart disease recommend the use of metoprolol for those conditions."

According to Smith, determining optimal treatment is important, given that so many people are undergoing noncardiac surgery. When it comes to treating patients, many questions remain. "Which beta-blocker are you going to use? [How soon before surgery] are you going to start it? How long will you continue it? . . . Do you just start the patient on a prespecified dose, or do you look for other manifestations of beta-blockade, such as heart rate in the 60s?"

Because most beta-blockers are generic, it may be difficult to get funding for a randomized clinical trial, but I "think it's a reasonable use of resources to try to get to the bottom of this," he concluded.

Revised guidelines expected in 2014

Dr Lee Fleisher (University of Pennsylvania, Philadelphia), chair, and Dr Kirsten E Fleischmann (University of California, San Francisco Medical Center), cochair of the committee revising the ACCF/AHA perioperative cardiovascular guidelines, said they were unable to comment on this paper.

However, Fleisher said in an interview that the paper is timely. "We have set up an evidence review committee to examine the beta-blocker question, and clearly publication of this paper will be used by that committee as part of our evidence review. . . . This will be incorporated in that update, which we hope to have published in 2014."

London reported receiving an unrestricted grant from the Anesthesia Patient Safety Foundation . Disclosures for the coauthors are listed in the paper. No other conflicts of interest were reported.

 

 

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