Safety and Effectiveness of Antidysrhythmic Drugs for Pharmacologic Cardioversion of Recent-Onset Atrial Fibrillation: a Systematic Review and Bayesian Network Meta-analysis

Purpose: The available evidence to determine which antidysrhythmic drug is superior for pharmacologic cardioversion of recent-onset (onset within 48 h) atrial fibrillation (AF) is uncertain. We aimed to identify the safest and most effective agent for pharmacologic cardioversion of recent-onset AF in the emergency department. Methods: We searched MEDLINE, Embase, and Web of Science from inception to February 21, 2023 (PROSPERO: CRD42018083781). Eligible studies were randomized controlled trials that enrolled adult participants with AF ≤ 48 h, compared a guideline-recommended antidysrhythmic drug with another antidysrhythmic drug or a different formulation of the same drug or placebo and reported specific adverse events. The primary outcome was immediate, serious adverse event — cardiac arrest, sustained ventricular tachydysrhythmia, atrial flutter 1:1 atrioventricular conduction, hypotension, and bradycardia. Additional analyses included the outcomes of conversion to sinus rhythm within 4 h and 24 h. We extracted data according to PRISMA-NMA and appraised trials using Cochrane RoB 2. We performed Bayesian network meta-analysis (NMA) using a Markov Chain Monte Carlo method with random-effect model and vague prior distribution to calculate odds ratios with 95% credible intervals. We assessed confidence using CINeMA. We used surface under the cumulative ranking curve (SUCRA) to rank agent(s). Results: The systematic review initially identified 5545 studies. Twenty-five studies met eligibility criteria, and 22 studies (n = 3082) provided data for NMA, which demonstrated that vernakalant (SUCRA = 70.9%) is most likely to be safest. Additional effectiveness NMA demonstrated that flecainide (SUCRA = 89.0%) is most likely to be superior for conversion within 4 h (27 studies; n = 2681), and ranolazine-amiodarone IV (SUCRA 93.7%) is most likely to be superior for conversion within 24 h (24 studies; n = 3213). Confidence in the NMA estimates is variable and limited mostly by within-study bias and imprecision. Conclusions: Among guideline-recommended antidysrhythmic drugs, the combination of digoxin IV and amiodarone IV is definitely among the least safe for cardioversion of recent onset AF; flecainide, vernakalant, ibutilide, propafenone, and amiodarone IV are definitely among the most effective for cardioversion within 4 h; flecainide is definitely among the most effective for cardioversion within 24 h. Further, randomized controlled trials with predetermined and strictly defined, hemodynamic adverse event outcomes are recommended.