Learning from mistakes in clinical practice guidelines: the case of perioperative β-blockade

Abstract

For more than two decades, the role of beta-blockers in preventing cardiac complications after major surgery has been the subject of contentious scientific and policy debate. Based on two small but highly publicized randomized trials published in 1996 and 1999, prominent U.S. organizations embraced preoperative beta-blocker initiation as a “best practice” and an opportunity for widespread safety improvement. Yet only a few years later, expert recommendations regarding preoperative beta-blockers were revised and downgraded when subsequent research failed confirm promising early findings and called attention to potential harms associated with beta-blocker overuse. In this paper, we trace the history of preoperative beta-blocker recommendations as a case study in lessons to be learned from reversals of guideline recommendations based initially on evidence drawn from randomized, controlled trials. Ultimately, we find that the policy significance that stakeholders ascribed to early beta-blocker studies combined with the prestige that experts assigned to the randomized controlled trial as a form of evidence to short-circuit discourse on the risks of preoperative beta-blocker initiation and led it to be elevated prematurely as a best practice. As such, the story of preoperative beta-blockers illustrates threats to objectivity in guidelines that can emerge from policy imperatives that lend primacy to the rapid translation of research into practice and from perspectives that unduly emphasize the strengths of randomized trials.

Keywords: Anaesthesia; Evidence-based medicine; Performance measures; Surgery.

Figure 1. Timeline of recommendations made by three U.S. organizations regarding preoperative beta-blocker initiation, 1997-2013

Items highlighted in green indicate statements broadening the indications for preoperative beta-blocker initiation; items in yellow indicate statements restricting these indications. The broken line charts the cumulative number of patients randomized to preoperative beta-blockers versus placebo across six key trials (lead author in parentheses): (A) Multicenter Study of Perioperative Ischemia (McSPI) atenolol study (Mangano) ; (B) Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE-I; Poldermans); (C) Perioperative Beta Blockade (POBBLE; Brady); (D) Diabetic Postoperative Morbidity and Mortality (DiPOM; Juul) ; (E) Metoprolol After Vascular Surgery (MaVS; Yang); (F) PeriOperative Ischemic Evaluation (POISE; Devereaux). As shown, statements in favor of expanding beta-blocker use from 1997 through 2002 occurred at a time when a relatively small number of patients had been studied randomized trials; as further evidence appeared between 2005 and 2008, guideline statements were revised to recommend more restricted use of preoperative beta-blockers. Abbreviations: ACP: American College of Physicians; AHRQ: U.S. Agency for Healthcare Research and Quality; ACC/AHA: American College of Cardiology/American Heart Association.