Perioperative Beta-Blockade Requires Further Study – Not Standard of Care

Bruce Kleinman, MD

To the Editor

I would like to respond to Dr. Royster’s lead article published in the Summer 2002 APSF Newsletter, touting the potential benefit of perioperative beta-blockade.1 I agree that “. . . it seems logical that beta-blockade might be beneficial during the stressful surgical period.”1 However, interventions that seem logical, rational, and, therefore, beneficial, sometimes surprise us, and ultimately turn out, not only not helpful, but indeed harmful. Witness the “rational” treatment of arrhythmias during myocardial infarction with antiarrhythmic drug therapy. That was ultimately proven harmful by the CAST trial.2 More recently, we all thought that hormone replacement therapy was a logical and beneficial treatment for women undergoing menopause, until recently proven otherwise by a large, randomized controlled trial.3

If we look closely at the outcome data for the use of beta-blockade in the perioperative period, we see there are only 3 studies (to the best of my knowledge) that directly addressed the question of whether beta-blockade affects perioperative outcome. Ischemia is not an outcome, myocardial infarction and death are. As such, Mangano showed no difference in in-hospital mortality between those receiving perioperative beta-blockade versus those not receiving beta-blockade.4 The two groups in that study showed different outcomes months to years after surgery, in a mere 200 patients. Clearly, a much larger study is needed. Poldermans did show a remarkable reduction in in-hospital adverse outcomes between the beta-blockade treated group versus the “standard” treatment group.5 However, one of the controversial aspects of his study was the fact that the “standard-treatment” group had 17% adverse outcomes; an adverse event rate much higher than most of us would expect.5 Could Poldermans’ findings be due to an idiosyncratic high event rate in the control group (standard treatment) and not an efficacious effect of beta-blockade in the experimental group? We do not know the answer. Urban (in an underpowered study involving a “low risk” group of patients) found no difference in primary outcomes (myocardial infarction and death) between patients treated postoperatively with beta-blockers versus those who were not.6 In addition, several recent observational studies have shown no protective effect of perioperative beta-blockade. In a subgroup of patients with extensive dobutamine-induced wall motion abnormalities, cardiac complications occurred in 36% of patients receiving perioperative beta-blockers and in 33% of those who were not receiving beta-blockers.7 In a re-evaluation of the incidence of myocardial infarction after noncardiac surgery, Badner, showed that perioperative beta-blockade was not protective.8 Finally, Lee in a prospective analysis of over 2500 patients showed no difference in cardiac complications between those receiving preoperative beta-blockade and those patients who were not.9 Clearly what we have here is the need for a large randomized controlled trial—trials for which the Veterans Affairs Cooperative Studies program are world famous. In the meantime, I would hold off labeling perioperative beta-blockade therapy with the emotionally laden medical legal term: “standard of care.” Yes, there is reasonable evidence supporting the use of perioperative beta-blockade. I believe, however, for the reasons I cited above, that competent and equally good practitioners can still differ. One can still believe that perioperative beta-blockade is not indicated in moderate to high-risk patients presenting for noncardiac surgery.

Bruce Kleinman, MD
Hines, Illinois

References

  1. Royster RL. Perioperative beta-blockade can reduce morbidity and mortality. APSF Newsletter 2002;17:21-23.
  2. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators. N Engl J Med 1989;321:406-12.
  3. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321-33.
  4. Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med 1996;335:1713-20.
  5. Poldermans D, Boersma E, Bax JJ, et al. The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med 1999;341:1789-94.
  6. Urban MK, Markowitz SM, Gordon MA, et al. Postoperative prophylactic administration of beta-adrenergic blockers in patients at risk for myocardial ischemia. Anesth Analg 2000;90:1257-61.
  7. Boersma E, Poldermans D, Bax JJ, et al. Predictors of cardiac events after major vascular surgery: Role of clinical characteristics, dobutamine echocardiography, and beta-blocker therapy. JAMA 2001;285:1865-73.
  8. Badner NH, Knill RL, Brown JE, et al. Myocardial infarction after noncardiac surgery. Anesthesiology 1998;88:572-8.
  9. Lee TH, Marcantonio ER, Mangione CM, et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 1999;100:1043-9.