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

Background: Intravenous beta-blockers are commonly used to manage patients with acute atrial fibrillation (AF) and atrial flutter (AFl), but the choice of specific agent is often not evidence-based.

Methods: A prospectively-registered systematic review and meta-analysis of randomised trials (PROSPERO: CRD42020204772) to compare the safety and efficacy of intravenous beta-blockers against alternative pharmacological agents.

Results: Twelve trials comparing beta-blockers with diltiazem, digoxin, verapamil, anti-arrhythmic drugs and placebo were included, with variable risk of bias and 1152 participants. With high heterogeneity (I² = 87%; p < 0.001), there was no difference in the primary outcomes of heart rate reduction (standardised mean difference − 0.65 beats/minute compared to control, 95% CI − 1.63 to 0.32; p = 0.19) or the proportion that achieved target heart rate (risk ratio [RR] 0.85, 95% CI 0.36–1.97; p = 0.70). Conventional selective beta-1 blockers were inferior for target heart rate reduction versus control (RR 0.33, 0.17–0.64; p < 0.001), whereas super-selective beta-1 blockers were superior (RR 1.98, 1.54–2.54; p < 0.001). There was no significant difference between beta-blockers and comparators for secondary outcomes of conversion to sinus rhythm (RR
1.15, 0.90–1.46; p = 0.28), hypotension (RR 1.85, 0.87–3.93; p = 0.11), bradycardia (RR 1.29, 0.25–6.82; p = 0.76) or adverse events leading to drug discontinuation (RR 1.03, 0.49–2.17; p = 0.93). The incidence of hypotension and bradycardia were greater with non-selective beta-blockers (p = 0.031 and p < 0.001).

Conclusions: Across all intravenous beta-blockers, there was no difference with other medications for acute heart rate control in atrial fibrillation and flutter. Efficacy and safety may be improved by choosing beta-blockers with higher beta-1 selectivity.