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

  • Original Research Article
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American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Background

β-Adrenergic receptor antagonists (β-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 β-blockers on mortality in patients undergoing non-cardiac surgery have yielded conflicting results.

Objective

This study aimed to examine the effect of perioperative β-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 β-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 β-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 β-blockers in patients treated with emergency and vascular surgery (high-risk category) whereas 15 and five trials evaluated the effect of β-blockers in intermediate low and intermediate high surgical risk categories, respectively. Subgroup analyses showed that the surgical risk category and dose titration of β-blockers to target heart rate affected the estimate of the effect of β-blockers for all-cause and cardiovascular mortality. β-Blockers reduced total mortality by 61% more in patients who underwent high-risk surgery than in those who underwent intermediate high- or intermediate low-risk surgery. When cardiovascular mortality was assessed, the benefit of β-blockers was 74% greater in trials that titrated β-blockers to heart rate than in trials that did not, although formal statistical significance was not achieved.

Conclusions

These data suggest that β-blockers may be useful for reducing mortality in patients who undergo high-risk non-cardiac surgery.

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Acknowledgments

This study was funded in part by the non-profit organization Fondazione Umbra Cuore e pertensione-ONLUS, Perugia, Italy. The authors have no conflicts of interest that are directly relevant to the content of this study.

Author information

Authors and Affiliations

  1. Department of Cardiology, Clinical Research Unit /3- Preventive Cardiology, Hospital ‘Santa Maria della Misericordia’, Perugia, Italy

    Fabio Angeli & Giovanni Mazzotta

  2. Department of Medicine, Hospital of Assisi, Assisi, Italy

    Paolo Verdecchia

  3. Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India

    Ganesan Karthikeyan

  4. Department of Internal Medicine, The Medical School, University of Perugia, 06126, Perugia, Italy

    Giorgio Gentile &  Gianpaolo Reboldi

Authors
  1. Fabio Angeli
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  2. Paolo Verdecchia
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  3. Ganesan Karthikeyan
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  4. Giovanni Mazzotta
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  5. Giorgio Gentile
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  6. Gianpaolo Reboldi
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Corresponding author

Correspondence to Gianpaolo Reboldi.

Appendix

Appendix

List of excluded trials (n = 49)

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Angeli, F., Verdecchia, P., Karthikeyan, G. et al. β-Blockers Reduce Mortality in Patients Undergoing High-Risk Non-Cardiac Surgery. Am J Cardiovasc Drugs 10, 247–259 (2010). https://doi.org/10.2165/11539510-000000000-00000

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