Efficacy of betablockers in patients with acute coronary syndrome: a systematic review and meta analysis of randomized trials
Authors: Zamiri N , Alradaddi H , Adli T , Jolly S , Ainsworth C , Whitlock R , Panchal P , Chen M , Mehta S , Belley-Cote E 
Published: November 2020

Abstract

Background
Since the inception of clinical guidelines on the management of patients with acute coronary syndrome (ACS), betablocker therapy has been included as a class I recommendation. However, most studies evaluating betablockers in ACS were conducted in the pre-reperfusion era. Currently, the great majority of patients undergo reperfusion and secondary prevention therapy has evolved; the impact of treatment with a betablocker in these patients may be different.

Purpose
We conducted a systematic review and meta-analysis to evaluate the impact of betablockers on mortality in patients after an ACS in the reperfusion era.

Methods
We searched MEDLINE, EMBASE, and Cochrane Central Registry of Controlled Trials for RCTs from inception to September 2019. We included randomized controlled trials comparing betablockers to no betablockers in adult patients presenting with an ACS. Independently and in duplicate, we screened titles and abstracts, reviewed the full-text report of potentially eligible studies and extracted data. Two reviewers also evaluated the risk of bias in duplicate. Disagreements were addressed by consensus. We considered trials to be conducted in the reperfusion era if reperfusion was attempted in more than 50% of patients, either with thrombolytics or primary angioplasty. Our primary outcome of interest was all-cause mortality. Secondary outcomes included hospitalization for heart failure, nonfatal myocardial infarction, stroke and cardiogenic shock. We pooled trial outcomes using a fixed effects model. The study protocol is registered with PROSPERO (CRD42019143158).

Results
After the initial screening of 10,969 references and full-text review of 176 articles, nine RCTs comprising a total of 49,639 patients with ACS were eligible for the final analysis. Predominantly, these patients presented with ST elevation myocardial infarction. Treatment with a betablocker did not improve all-cause mortality at 30 days (risk ratio (RR) 0.98 [95% CI 0.92–1.04], I2=44%), or at longest follow up (up to three years) with RR 0.97 ([95% CI 0.91–1.03], I2=0%). Betablocker therapy was associated with an increased risk of HF hospitalization (RR 1.10 [95% CI 1.05–1.15], I2=52%) and cardiogenic shock during index hospitalization (RR 1.29, [95% CI 1.18–1.40], I2=0%). However, betablocker therapy reduced the risk of nonfatal myocardial infarction (RR 0.72 [95% CI 0.63–0.83], I2=0%); it did not impact the risk of stroke (RR 1.13 [95% CI 0.95–1.35], I2=0%).

Conclusion
In the reperfusion era, betablocker therapy after an ACS does not appear to improve short or long-term survival. Although betablocker therapy was associated with a reduction in nonfatal myocardial infarction, it increased the risk of heart failure hospitalization and cardiogenic shock. In light of these findings, clinical guidelines should reconsider the strength of their recommendation for betablocker use in the ACS population until further contemporary evidence is available.

Funding Acknowledgement
Type of funding source: None