Efficacy and safety of intravenous beta-blockers in acute atrial fibrillation and flutter is dependent on beta-1 selectivity: a systematic review and meta-analysis of randomised trials
Authors: Perrett M , Gohil N , Tica O , Bunting K.V , Kotecha D 
Published: October 2021

Abstract

Background
Intravenous (IV) beta-blockers are commonly used to manage patients with acute atrial fibrillation (AF) and atrial flutter (AFl). Important pharmacodynamic differences exist amongst beta-blockers, and the choice of beta-blocker or other therapy is often not evidence-based.

Purpose
Systematic review and meta-analysis of randomised controlled trials (RCTs) in the setting of acute AF/AFl to assess the efficacy and safety of IV beta-blockers against other pharmacological interventions (diltiazem, verapamil, digoxin, anti-arrhythmic drugs or placebo).

Methods
Prospectively registered (PROSPERO: CRD42020204772). MEDLINE, EMBASE and Cochrane Register were searched from inception to August 2020. The primary outcomes were reduction in heart rate and proportion of patients achieving study-defined target heart rate. Secondary outcomes included conversion to sinus rhythm and incidence of adverse events. Beta-blockers were divided according to beta-1 adrenoreceptor selectivity. Meta-analysis was performed to calculate risk ratios (RR) and standardised mean differences (SMD) using random-effects, and fixed-effects within beta-1 subgroups.

Results
From 5974 studies, 12 RCTs were included with variable risk of bias, encompassing 1152 participants with mean age 62 years, 38% women and baseline heart rate 137 beats/minute. With high heterogeneity (I2=87%; p&lt;0.001), there was no difference in the reduction in heart rate between beta-blockers and comparators (SMD −0.65, 95% CI −1.63–0.21; p=0.19), and no difference in the proportion that achieved target heart rate (RR 0.85, 95% CI 0.36–1.97; p=0.70). Analysis by beta-1 selectivity demonstrated that conventional beta-1 blockers (metoprolol, esmolol) were inferior for target heart rate reduction (RR 0.33, 95% CI 0.17–0.64; p=0.001), whereas super-selective agents (landiolol) were superior (RR 1.98, 95% CI 1.54–2.54; p&lt;0.001). There was no difference in the rate of conversion to sinus rhythm between beta-blockers and comparators (RR 1.15, 95% CI 0.92–1.44; p=0.21). Adverse events were similar in both groups overall, with no significant difference in hypotension (RR 1.74, 95% CI 0.85–3.58; p=0.13), bradycardia (RR 0.86, 95% CI 0.19–3.81; p=0.153) or events leading to drug discontinuation (RR 1.16, 95% CI 0.26–5.15; p=0.84). Assessment by beta-1 selectivity showed that hypotension and bradycardia were more frequent with non-selective beta-blockers (sotalol) than comparators (RR 4.57, 95% CI 1.92–10.85; p=0.001 and 5.97, 95% CI 1.34–26.57; p=0.019).

Conclusion
There is no difference between IV beta-blockers overall and other medications for the control of acute AF/AFl, although better efficacy was shown for beta-blockers with higher beta-1 selectivity. IV beta-blockers were as safe as comparator agents, with the exception of non-selective beta-blockers.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Independent systematic review commissioned by Amomed Pharma. Target heart rate and hypotension events