Benefit of Perioperative Beta Blockers Confirmed in Large Study

October 23, 2009 (New Orleans, Louisiana) — Findings from a huge database at the San Francisco Veterans Administration (VA) Hospital, presented here at the American Society of Anesthesiologists 2009 Annual Meeting, confirmed the survival benefits of perioperative beta blockers for patients with cardiovascular risk.

More than 10 years ago, perioperative beta blockers were shown to reduce mortality in clinical trials and were therefore adopted as the standard of care by cardiology societies. Subsequently, at least 1 large study — the Perioperative Ischemic Evaluation (POISE) trial — called into question their benefit and, in fact, found an increased rate of mortality and stroke associated with their use (Devereaux PJ et al. American Heart Association 2007 Scientific Sessions. Abstract LBCT 20825).

Lead author of the current analysis, Arthur Wallace, MD, professor of anesthesiology and perioperative medicine at the University of California at San Francisco School of Medicine, finds flaws in the POISE trial, which he said could have affected the results, especially the use of metoprolol in a dose that is 8 times higher than the standard.

The study he and his colleagues developed and have disseminated widely is the Perioperative Cardiac Risk Reduction Therapy (PCRRT) protocol, which uses standard doses and incorporates several "basic rules" that have been shown to improve outcomes and that can be applied across hospital systems, he said.

Basics of PCCRT Protocol

Beta Blockers

Oral atenolol 25 mg once daily to start. If heart rate is higher than 60 beats per minute and systolic blood pressure is higher than 120 mm Hg, titrate dose to effect.
Atenolol or intravenous (IV) metoprolol on the day of surgery. Atenolol or IV metoprolol postop until taking orally.
Oral atenolol 100 mg once daily for 1 week or more postop.
If known coronary artery or peripheral vascular disease, continue beta blocker indefinitely.

If Unable to Take Beta Blockers

Oral clonidine 0.2 mg tablet the night before surgery.
Clonidine TTS 2 patch (0.2 mg/24 hours) the night before surgery.
Oral clonidine 0.2 mg tablet the morning of surgery.

"Our study tested the hypothesis that the administration of perioperative beta blockade using the protocol we developed at the San Francisco VA Medical Center would reduce the incidence of 30-day and 1-year mortality," Dr. Wallace said.

Data from all surgical procedures between 1996 and 2008 were extracted from the VA computerized database. Patients were identified for cardiovascular risk on the basis of the presence of known coronary artery or peripheral vascular disease, or the presence of 2 standard risk factors. Beta blocker use was analyzed as none, continuous (preoperative and postoperative administration), addition (no prehospital administration but beta blocker added on the day of surgery), or withdrawal (prehospital administration but none in hospital or after discharge).

Investigators analyzed 38,779 surgical procedures in 20,937 patients (average age, 63 years). For in-patient procedures, metoprolol was most common (75%); for out-patient procedures, atenolol was most common (54%).

When compared with no use of beta blockers, the prophylactic addition of beta blockers significantly reduced 30-day and 1-year mortality by approximately 50%, Dr. Wallace reported.

The odds ratios favoring beta blockers were 0.52 (95% confidence interval [CI], 0.33 - 0.83; P =.0055) for 30-day mortality and 0.64 (95% CI, 0.51 - 0.79; P =.0001) for 1-year mortality. Continuous use carried an odds ratio of 0.68 (95% CI, 0.47 - 0.98; P =.037) for mortality at 30 days and 0.82 (95% CI, 0.67 - 1.0; P =.05) at 1 year.

Withdrawal of beta blockers in patients already taking the drugs raised the risk for 30-day mortality almost 4-fold (P < .0001) and nearly doubled 1-year mortality (P > .0001).

Dr. Wallace added that clinicians should be aggressive in identifying candidates for beta blockers and starting them on therapy right away. "Patients scheduled for surgery start receiving a beta blocker as soon as we identify them as at-risk," he said.

Poster discussion moderator Gwendolyn Boyd, MD, professor of anesthesiology at the University of Alabama School of Medicine, Birmingham, noted that since the POISE results were announced, the use of beta blockers has become controversial again.

"There is a big tendency now to discontinue beta blockers when the patient is admitted," she said. "I've heard as many as 50% may be taken off these drugs. That is probably because of the conflicting data from POISE. Here, the VA study gives us convincing data of their benefit."

Dr. Wallace and Dr. Boyd have disclosed no relevant financial relationships.

American Society of Anesthesiologists (ASA) 2009 Annual Meeting: Abstract A705. Presented October 19, 2009.