How strong is the evidence for the use of perioperative beta blockers in non-cardiac surgery? Systematic review and meta-analysis of randomised controlled trials

Abstract

Objective: To determine the effect of perioperative beta blocker treatment in patients having non-cardiac surgery.

Design: Systematic review and meta-analysis.

Data sources: Seven search strategies, including searching two bibliographic databases and hand searching seven medical journals. STUDY SELECTION AND OUTCOMES: We included randomised controlled trials that evaluated beta blocker treatment in patients having non-cardiac surgery. Perioperative outcomes within 30 days of surgery included total mortality, cardiovascular mortality, non-fatal myocardial infarction, non-fatal cardiac arrest, non-fatal stroke, congestive heart failure, hypotension needing treatment, bradycardia needing treatment, and bronchospasm.

Results: Twenty two trials that randomised a total of 2437 patients met the eligibility criteria. Perioperative beta blockers did not show any statistically significant beneficial effects on any of the individual outcomes and the only nominally statistically significant beneficial relative risk was 0.44 (95% confidence interval 0.20 to 0.97, 99% confidence interval 0.16 to 1.24) for the composite outcome of cardiovascular mortality, non-fatal myocardial infarction, and non-fatal cardiac arrest. Methods adapted from formal interim monitoring boundaries applied to cumulative meta-analysis showed that the evidence failed, by a considerable degree, to meet standards for forgoing additional studies. The individual safety outcomes in patients treated with perioperative beta blockers showed a relative risk for bradycardia needing treatment of 2.27 (95% CI 1.53 to 3.36, 99% CI 1.36 to 3.80) and a nominally statistically significant relative risk for hypotension needing treatment of 1.27 (95% CI 1.04 to 1.56, 99% CI 0.97 to 1.66).

Conclusion: The evidence that perioperative beta blockers reduce major cardiovascular events is encouraging but too unreliable to allow definitive conclusions to be drawn.

Fig 1

Flowchart of randomised controlled trials through the systematic review

Fig 2

Relative risks for bradycardia needing treatment

Fig 3

Relative risks for major perioperative cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal cardiac arrest)

Fig 4

Cumulative meta-analysis assessing the effect of perioperative β blockers on the 30 day risk of major perioperative cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal cardiac arrest) in patients having non-cardiac surgery. The Lan-DeMets sequential monitoring boundary, which assumes a 10% control event rate and a 25% relative risk reduction with 80% power and a two sided α=0.01, has not been crossed, indicating that the cumulative evidence is inconclusive