The effects of differences among β-blockers and initiation times in patients undergoing noncardiac surgery (NCS) remain unknown. On June 1, 2012, the authors searched PubMed, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to identify all trials of perioperative β-blockers in patients undergoing NCS published between January 1960 and June 2012. The authors included only randomized, double-blind and placebo-controlled trials of perioperatively administered β-blockers (ie, during the pre-, intra- and/or postoperative period) in patients with at least 1 risk factor for coronary artery disease undergoing NCS. The endpoints of these trials had to include all-cause mortality, myocardial infarction (MI) and/or stroke. The authors identified 8 English-language publications, involving 11,180 patients, which fulfilled our inclusion criteria. Perioperative β-blocker therapy was associated with a significant decrease in patient risk of developing MI (relative risk [RR] = 0.73; 95% confidence interval [CI], 0.61-0.86) but a significant increase in risk of developing stroke (RR = 2.17; 95% CI, 1.35-3.50) versus placebo, resulting in a nonsignificant decrease in overall mortality (RR = 0.91; 95% CI, 0.60-1.36). Indirect comparisons demonstrated that perioperative atenolol therapy was associated with lower mortality and incidence of MI. β-blocker therapy initiated >1 week before surgery was associated with improved postoperative mortality. Perioperative β-blocker treatment of patients undergoing NCS increases the incidence of stroke but decreases the incidence of MI, leading to a nonsignificant decrease in mortality. The authors also observed that atenolol treatment or β-blocker therapy initiated >1 week before NCS was associated with improved outcomes.
BACKGROUND: Current European and American guidelines recommend the perioperative initiation of a course of β-blockers in those at risk of cardiac events undergoing high- or intermediate-risk surgery or vascular surgery. The Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) family of trials, the bedrock of evidence for this, are no longer secure. We therefore conducted a meta-analysis of randomised controlled trials of β-blockade on perioperative mortality, non-fatal myocardial infarction, stroke and hypotension in non-cardiac surgery using the secure data.
METHODS: The randomised controlled trials of initiation of β-blockers before non-cardiac surgery were examined. Primary outcome was all-cause mortality at 30 days or at discharge. The DECREASE trials were separately analysed.
RESULTS: Nine secure trials totalling 10 529 patients, 291 of whom died, met the criteria. Initiation of a course of β-blockers before surgery caused a 27% risk increase in 30-day all-cause mortality (p=0.04). The DECREASE family of studies substantially contradict the meta-analysis of the secure trials on the effect of mortality (p=0.05 for divergence). In the secure trials, β-blockade reduced non-fatal myocardial infarction (RR 0.73, p=0.001) but increased stroke (RR 1.73, p=0.05) and hypotension (RR 1.51, p<0.00001). These results were dominated by one large trial.
CONCLUSIONS: Guideline bodies should retract their recommendations based on fictitious data without further delay. This should not be blocked by dispute over allocation of blame. The well-conducted trials indicate a statistically significant 27% increase in mortality from the initiation of perioperative β-blockade that guidelines currently recommend. Any remaining enthusiasts might best channel their energy into a further randomised trial which should be designed carefully and conducted honestly.
OBJECTIVE: To re-evaluate the effects of perioperative beta-blockade on mortality and major outcomes after surgery.
DESIGN: A meta-analysis of parallel randomized, controlled trials published in English.
SETTING: A university-based electronic search.
PARTICIPANTS: Patients undergoing surgery.
INTERVENTIONS: Two interventions were evaluated: (1) Stopping or continuing a β-blocker in patients on long-term β-blocker therapy; and (2) Adding a β-blocker for the perioperative period.
MEASUREMENTS AND MAIN RESULTS: Stopping a β-blocker before the surgery did not change the risk of myocardial infarction (3 studies including 97 patients): risk ratio (RR), 1.08 (95% confidence interval 0.30, 3.95); I(2), 0%. Adding a β-blocker reduced the risk of death at 1 year: RR, 0.56 (0.31, 0.99); I(2), 0%; p = 0.046; number needed to treat 28 (19, 369) (4 studies with 781 patients). Adding a β-blocker reduced the 0-to-30 day risk of myocardial infarction: RR, 0.65 (0.47, 0.88); I(2), 12.9%; p = 0.006 (15 studies with 12,224 patients), but increased the risk of a stroke: RR, 2.18 (1.40, 3.38); I(2), 0%; p = 0.001 (8 studies with 11,737 patients); number needed to harm 177 (512, 88).
CONCLUSIONS: β-blockers reduced the 1-year risk of death, and this effect seemed greater than the risk of inducing a stroke.
BACKGROUND: Although β blockers have been found to decrease perioperative myocardial infarction (MI), β-blocker-mediated hypotension is associated with postoperative stroke and mortality. In this systematic review we assessed the safety and efficacy of the β1-specific, adrenergic receptor antagonist esmolol in noncardiac surgery. Safety was assessed by analyzing the incidence of postoperative hypotension and bradycardia, and efficacy was assessed by analyzing the incidence of myocardial ischemia.
METHODS: We searched electronic databases for randomized placebo-controlled trials of the perioperative use of esmolol in noncardiac surgery. We abstracted data on design, demographics, hemodynamic changes (planned or unplanned), myocardial ischemia, and MI. Heterogeneity was assessed via meta-regression.
RESULTS: Our search identified 67 trials, which were well matched for study characteristics. The quality of the studies was limited by small sample size and poorly defined allocation concealment. Overall, the analysis demonstrates an increased incidence of unplanned hypotension (OR 2.13; 95% confidence interval [CI], 1.48 to 3.04), which was found to be dose related (R(2) = 0.408). An increased incidence of significant bradycardia was not demonstrated (OR 1.18; 95% CI, 0.69 to 2.02). Dose titration was shown to influence both the change in arterial blood pressure and heart rate. In comparison with placebo, esmolol decreased the frequency of myocardial ischemia in the 7 evaluating studies (OR 0.17; 95% CI, 0.02 to 0.45). We did not assess the effects of esmolol on the incidence of MI or stroke because the incidence of these events was too infrequent in the retrieved studies.
CONCLUSION: This review suggests that titration of esmolol to a hemodynamic end point can be safe and effective. Safety data from studies in higher-risk patients are needed to establish a perioperative safety and efficacy profile of esmolol.
