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Perioperative beta-blockers in noncardiac surgery: Evolution of the evidence

Cleveland Clinic Journal of Medicine. 2008 July;75(7):513-519
July 1, 2008|Cleveland Clinic Journal of Medicine
Brian Harte, MD;Amir K. Jaffer, MD
Author and Disclosure Information

Brian Harte, MD
Clinical Assistant Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western University; Chairman, Department of Hospital Medicine, Cleveland Clinic

Amir K. Jaffer, MD
Associate Professor of Medicine; Chief, Division of Hospital Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL

Address: Brian Harte, MD, Department of Hospital Medicine, S70, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail harteb@ccf.org

ABSTRACTAfter studies in the 1990s suggested that beta-blockers offer substantial benefits when given before surgery, several national organizations endorsed the perioperative use of these drugs as a best practice in certain patients. However, subsequent research has cast doubt on whether it is appropriate to use these drugs as widely as suggested by those early studies.

KEY POINTS

  • Beta-blockers reduce perioperative ischemia, but the benefit may be only in high-risk patients undergoing high-risk surgery. Currently, the best evidence supports their use in two groups: patients undergoing vascular surgery who have known ischemic heart disease or multiple risk factors for it, and patients who are already on beta-blockers.
  • The Perioperative Ischemic Evaluation (POISE) findings suggest that beta-blockers should be used in the immediate preoperative period only with great caution, after ensuring that the patient is clinically stable and without evidence of infection, hypovolemia, anemia, or other conditions that could make heart-rate titration misleading or use of the drug dangerous.
  • When feasible, beta-blockers should be started a month before surgery, titrated to a heart rate of 60 beats per minute, and continued for approximately a month. If the drug is then to be discontinued, it should be tapered slowly.

EARLY CLINICAL EVIDENCE IN FAVOR OF PERIOPERATIVE BETA-BLOCKER USE

Evidence in patients at high risk

Mangano et al,2 in a study published in 1996, randomized 200 patients with known coronary disease or established risk factors for it who were undergoing noncardiac surgery to receive the beta-blocker atenolol orally and intravenously or placebo in the immediate perioperative period. Fewer patients in the atenolol group died in the first 6 months after hospital discharge (0 vs 8%, P < .001), the first year (3% vs 14%, P = .005), and the first 2 years (10% vs 21%, P = .019). However, there was no difference in short-term outcomes, and the study excluded patients who died in the immediate postoperative period. If these patients had been included in the analysis, the difference in the death rate at 2 years would not have been statistically significant.26 Other critical findings: more patients in the atenolol group were using angiotensin-converting enzyme inhibitors and beta-blockers when they were discharged, and the placebo group had slightly more patients with prior myocardial infarction or diabetes.27 (Atenolol is available in the United Sates as Tenormin and generically.)

Poldermans et al,3 in a study published in 1999, randomized 112 vascular surgery patients to receive either oral bisoprolol or placebo. These patients were selected from a larger cohort of 1,351 patients on the basis of high-risk clinical features and abnormal results on dobutamine echocardiography. Bisoprolol was started at least 1 week before surgery (range 7–89 days, mean 37 days), and patients were reevaluated before surgery so that the dose could be titrated to a goal heart rate of less than 60 beats per minute. After surgery, the drug was continued for another 30 days. The study was stopped early because the bisoprolol group had a 90% lower rate of non-fatal myocardial infarction and cardiac death at 30 days. Despite the study’s limitation (eg, enrolling selected patients and using an unblinded protocol), these compelling findings made a strong case for the use of beta-blockers perioperatively in patients at high risk, ie, those with ischemic heart disease who are undergoing major vascular surgery. (Bisoprolol is available in the United States as Zebeta and generically)

Evidence in patients at intermediate risk

Boersma et al28 performed a follow-up to the study by Poldermans et al, published in 2001, in which they analyzed characteristics of all 1,351 patients who had been originally considered for enrollment. Using regression analysis, they identified seven clinical risk factors that predicted adverse cardiac events: angina, prior myocardial infarction, congestive heart failure, prior stroke, diabetes, renal failure, and age 70 years or older. Furthermore, for the entire cohort, patients receiving beta-blockers had a lower risk of cardiac complications (0.8%) than those not receiving beta-blockers (2.3%). In particular, the patients at intermediate risk (defined as having one or two risk factors) had a very low event rate regardless of stress test results, provided they were on beta-blockers: their risk of death or myocardial infarction was 0.9%, compared with 3.0% for those not on beta-blockers.

The authors concluded that dobutamine stress testing may not be necessary in patients at intermediate risk if beta-blockers are appropriately prescribed. However, others took issue with their data and conclusions, arguing that there have been so few trials that the data are still inconclusive and inadequate to ascertain the benefit of perioperative beta-blockade, particularly in patients not at high risk.26,29

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