ABSTRACT & COMMENTARY
Beta-Blockers in CAD Patients Undergoing Non-Cardiac Surgery
By Michael H. Crawford, MD
Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco
This article originally appeared in the May 2014 issue of Clinical Cardiology Alert. It was peer reviewed by Ethan Weiss, MD, Assistant Professor of Medicine, Division of Cardiology and CVRI, University of California, San Francisco. Dr. Crawford reports no financial relationships relevant to this field of study, and Dr. Weiss is a scientific advisory board member for Bionovo.
Source: Andersson C, et al. Association of beta-blocker therapy with risks of adverse cardiovascular events and deaths in patients with ischemic heart disease undergoing noncardiac surgery: A Danish nationwide cohort study. JAMA Intern Med 2014;174:336-344.
Whelton SP, Bansal S. Perioperative beta-blockers revisited: Good for what ails you? JAMA Intern Med 2014;174:345-346.
Recent controversy has erupted concerning the use of prophylactic beta-blockers in patients with known or suspected coronary artery disease (CAD) undergoing non-cardiac surgery. Thus, these investigators from Stanford University and Denmark analyzed the Danish National Patient Registry for patients with a history of ischemic heart disease who underwent non-cardiac surgery from 2004-09. Two cohorts were identified, those with and without heart failure. Among those without heart failure, patients were further grouped as to whether they had had a myocardial infarction (MI) or not. Of the 28,263 surgeries included in this analysis, 7990 (28%) were in patients with heart failure, 12,601 (45%) who had a prior MI, 3964 (14%) who had prior coronary bypass surgery, and 6760 (24%) who had a percutaneous intervention. Orthopedic surgery was most common (40%), followed by abdominal surgery (20%); 33% were urgent or emergent. Beta-blockers were prescribed for 41% of the patients.
Sophisticated statistical techniques were used: multivariate analysis, propensity matching, and sensitivity analyses. Five percent of the patients experienced a major adverse cardiac or cerebral event (MACCE). These major events included death (75%), stroke (3.5%), and MI (22%). MACCE were more common in the heart failure patients (10% vs 3%). Beta-blocker use overall did not significantly affect outcomes (adjusted MACCE hazard ratio [HR], 0.90; 95% CI, 0.79-1.02). In heart failure patients, beta-blocker use reduced MACCE (HR, 0.78; 95% CI, 0.66-0.91). Among the patients without heart failure, a recent MI (< 2 years) favored beta-blocker therapy (MACCE HR, 0.54; 95% CI, 0.37-0.78). Patients with a history of revascularization did not benefit from beta-blocker therapy. The type of surgery did not influence the results of beta-blocker therapy. The authors concluded that among those with ischemic heart disease, 30-day MACCE was only improved by beta-blockers in those with heart failure or recent MI.
The concept that excess adrenergic tone during and after surgery could lead to cardiac events in susceptible individuals such as those with ischemic heart disease and that beta-blocker therapy in the perioperative period may abrogate this risk is attractive. Early randomized trials, although small, supported this hypothesis and beta-blockers quickly became the go-to intervention for preventing perioperative MI and death, especially in known CAD patients undergoing moderate-to-high risk surgery. The 2009 European Society of Cardiology (ESC) Guidelines recommend beta-blockers for all CAD patients and the American College of Cardiology/American Heart Association (ACC/AHA) guidelines from the same year recommend beta-blockers in CAD patients undergoing high-risk surgery (class IIa), and if a patient is already on beta-blockers to continue them (class I). However, newer studies have shown an increased risk of bradycardia and hypotension with beta-blockers and no consistent reduction in adverse cardiovascular events. This raises the question of whether we have pushed this concept too far (into lower-risk individuals) or whether it is no longer of value with modern anesthesia and surgical care.
This study addresses these issues by analyzing a large registry database from Denmark of patients with ischemic heart disease undergoing non-cardiac surgery. They found that beta-blockers were only beneficial in those with heart failure or recent MI. Neither prior revascularization nor the type of surgery influenced the results. The results make sense in that heart failure and recent MI are strong indications for beta-blockers in all patients. This would support the ACC/AHA class I indications for beta-blockers in those who already have an indication for them, but not the class IIa and ESC recommendation for all CAD patients undergoing major surgery. Also, prior revascularization seems to be protective as beta-blockers were ineffective in these patients.
The strengths of this study are the large population of unselected patients and the sophisticated analyses that were done to offset the non-randomized study design limitation. These registry studies are becoming more popular and complex as we realize that many clinical questions, such as the ones studied here, will never be subjected to a randomized trial. Other weaknesses of this study are the lack of information on drug doses, compliance, and adverse effects. Also, we don’t know how ischemic heart disease and heart failure were diagnosed; these categories were determined using administrative data from ICD codes and not directly from chart review.
This study adds to the body of literature on this topic and supports the ACC/AHA class I medication for perioperative beta-blockers in those who already have an indication for their use. It does not support beta-blockers for all CAD patients undergoing major surgery, but doesn’t preclude the judicious use of them in selected high-risk patients. Selective therapy fits the new mantra of personalized medicine.