When Guidelines Need Guidance
…
Article Outline
In October 2007, the newly drafted American College of Cardiology (ACC) and American Heart Association (AHA) guidelines on perioperative cardiovascular evaluation for noncardiac surgery were published simultaneously in Circulation and the Journal of the American College of Cardiology.1 Surprisingly, the guidelines continued to recommend β-blocker therapy perioperatively by stating “Although many of the randomized controlled trials of beta blocker therapy are small, the weight of evidence—especially in aggregate—suggests a benefit to perioperative beta blockade during noncardiac surgery in high-risk patients.”1 As a consequence, the Physicians Consortium for Performance Improvement and the Surgical Care Improvement Project of the American Medical Association have established perioperative β-blockade as a quality measure.2 This means that practicing physicians not following the guidelines (ie, not prescribing perioperative β-blockers) potentially can be penalized and are at increased risk for litigation. This also means that the evidence underlying the above statement should be ironclad, particularly in view of the fact that the number of noncardiac surgical procedures amounts to about 6 million per year in the United States and about a quarter of them have been associated with a significant perioperative cardiovascular risk.
Of note, the guidelines were published a month before the results of the prospective randomized, Perioperative Ischemic Evaluation (POISE) trial became available.3 The POISE trial clearly supersedes all previous trials because of its thorough design and its being more than twice as large than all 30 previous trials together. However, a closer look at even the (pre POISE) data by evaluating only trials which were available to the guidelines committee to make their recommendations suggests there was no benefit of perioperative blockade for noncardiac surgery. Among 30 randomized controlled trials which evaluated 3781 patients, β-blockers failed to show any significant benefit for any of the hard efficacy outcomes–all-cause mortality (P=.606), cardiovascular mortality (P=.342), stroke (P=.175), or heart failure (P=.348) with a trend towards reduction in the risk for nonfatal MI (P =.05) when compared to placebo.4 However, β-blockers reduced the risk of the soft end point of myocardial ischemia (RR 0.48; 95% CI, 0.34-0.69) but with a 134% and 32% increased risk of perioperative bradycardia and hypotension (requiring treatment) (Figure).
Figure.
Meta-analysis of RCTs of perioperative β-blockers for noncardiac surgery (pre POISE). BB
=beta blockers; T=serious adverse effect requiring treatment. There was no beneficial effect of β-blockers when compared to placebo/standardized care for any of the secondary outcomes with an increased risk of perioperative bradycardia and hypotension.
The inefficacy of β-blockers to reduce the perioperative cardiovascular risk is now confirmed by the landmark POISE trial,3 which was a randomized controlled trial of metoprolol vs placebo in 8351 patients 45 years or older with or at risk of atherosclerotic disease undergoing noncardiac surgery. Perioperative β-blockade was associated with a 30% reduction in the risk of nonfatal myocardial infarction at the expense of 33% increased risk of all-cause mortality and a 117% increased risk of stroke. Thus, the current body of evidence, pre and post POISE, in aggregate, fails to support the use of β-blockers for the prevention of perioperative hard clinical outcomes. Of note, the wording of the guidelines of the European Society of Cardiology was somewhat more cautious in stating that “Although these studies were small and do not provide definite answers, the results suggest an improved outcome (with β-blockers) especially in high-risk patients.5
Given this state-of-the-art, one may appropriately ask as to the exact reason why the ACC/AHA guidelines were published. Not only were they not based on available evidence, but they also were not timely because they were outdated only a few weeks after publication, when more definite evidence became available or at least was accessible. As the ACC/AHA states in their preamble, 1 “guidelines should be based on both rigorous and expert analysis of the available data documenting absolute and relative benefits and risk of those procedures and therapies” and “guidelines should improve the effectiveness of care, optimize patient's outcomes, and favorably affect the overall cost of care by focusing resources of the most effective strategies.” Neither one of these statements seems to apply to the latest draft of the above ACC/AHA guidelines. Practicing physicians can find more than 2000 guidelines in the National Guideline Clearinghouse (www.guideline.gov). Clearly they are neither infallible nor should they be considered a substitute for clinical judgment. Guidelines have been criticized for being too dogmatic or not dogmatic enough. However when dogma is no longer evidence based, we expect guidelines to reflect the new evidence swiftly and unambiguously. Regrettably this was not the case in the above ACC/AHA guidelines.
References
- ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): Developed in Collaboration With the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. Circulation. 2007;116(17):1971–1996
- . http://www.ama-assn.org/ama/pub/category/2946.html2007;Accessed December 20, 2007
- POISE Trial Investigators, Devereaux PJ, Yang H, Guyatt GH, et al. Rationale, design, and organization of the PeriOperative ISchemic Evaluation (POISE) trial: a randomized controlled trial of metoprolol versus placebo in patients undergoing noncardiac surgery. Paper presented at American Heart Association November 2007, Orlando, Fla.
- Role of Peri-Operative Beta-Blockers in Patients Undergoing Non-cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials (abstr). Circulation. 2007;116(16):II-324
- Expert consensus document on beta-adrenergic receptor blockers. Eur Heart J. 2004;25(15):1341–1362
PII: S0002-9343(08)00489-0
doi:10.1016/j.amjmed.2008.04.031
© 2008 Elsevier Inc. All rights reserved.
