β-Blockers Reduce Mortality in Patients Undergoing High-Risk Non-Cardiac Surgery

Background: beta-Adrenergic receptor antagonists (beta-blockers) are frequently used with the aim of reducing perioperative myocardial ischemia and infarction. However, randomized clinical trials specifically designed to evaluate the effects of beta-blockers on mortality in patients undergoing non-cardiac surgery have yielded conflicting results. Objective: This study aimed to examine the effect of perioperative beta-blockers on total and cardiovascular mortality in patients undergoing non-cardiac surgery. Methods: We conducted a meta-analysis of randomized clinical trials that examined the effects of beta-blockers versus placebo on cardiovascular and all-cause mortality in patients undergoing non-cardiac surgery. We extracted data from articles published before 30 November 2009 in peer-reviewed journals indexed in MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and CINAHL. Data extraction was carried out independently by two reviewers on the basis of an intent-to-treat approach, and inconsistencies were discussed and resolved in conference. The present meta-analysis was undertaken according to the Quality of Reporting of Meta-analyses (QUORUM) statement. Results: A total of 2148 records were screened, from which we identified 74 randomized controlled trials for non-cardiac surgery. After excluding 49 studies that did not report the clinical outcome of interest or were subanalyses or presented duplicate data, the final search left 25 clinical trials. Treatment with beta-blockers had no significant effect on all-cause mortality (odds ratio [OR] 1.15; 95% confidence interval [CI] 0.92, 1.43; p = 0.2717) or cardiovascular mortality (OR 1.13; 95% CI 0.85, 1.51; p = 0.5855). However, surgical risk category markedly differed across the studies. According to Joint American College of Cardiology and American Heart Association guidelines for perioperative assessment of patients having non-cardiac surgery, five trials evaluated the effect of beta-blockers in patients treated with emergency and vascular surgery (high-risk category) whereas 15 and five trials evaluated the effect of beta-blockers in intermediate low and intermediate high surgical risk categories, respectively. Subgroup analyses showed that the surgical risk category and dose titration of beta-blockers to target heart rate affected the estimate of the effect of beta-blockers for all-cause and cardiovascular mortality. beta-Blockers reduced total mortality by 61% more in patients who underwent highrisk surgery than in those who underwent intermediate high- or intermediate low-risk surgery. When cardiovascular mortality was assessed, the benefit of beta-blockers was 74% greater in trials that titrated beta-blockers to heart rate than in trials that did not, although formal statistical significance was not achieved. Conclusions: These data suggest that beta-blockers may be useful for reducing mortality in patients who undergo high-risk non-cardiac surgery.