Association of Concurrent Amiodarone and Beta-Blocker Therapy at Discharge With 30-Day Rehospitalization After Atrial Fibrillation Hospitalization

Background Atrial fibrillation (AF) is associated with high early rehospitalization rates following index hospitalization. While beta-blockers remain the cornerstone of rate control, amiodarone is frequently used for rhythm control in selected patients. The clinical impact of concurrent amiodarone and beta-blocker therapy at discharge on short-term rehospitalization remains incompletely defined. Methods A retrospective cohort study using the TriNetX platform was conducted. Adult patients hospitalized with AF were identified and stratified based on discharge prescription of amiodarone plus a beta-blocker versus comparator therapy. Strict exclusion criteria were applied to minimize confounding, including exclusion of patients with recent cardiac surgery, implantable device placement, advanced conduction disease, or incomplete follow-up. Propensity score matching in a 1:1 ratio was performed using demographic and clinical variables. The primary outcome was 30-day all-cause rehospitalization. Secondary outcomes included AF-related rehospitalization, rhythm-related interventions, and safety endpoints. Results A total of 2,647 patients met the inclusion criteria. After propensity score matching, 1,323 patients per group were successfully matched, yielding a final analytic sample of 2,646 patients; one patient could not be matched and was excluded. Baseline characteristics were well balanced, with standardized mean differences below 0.10. At 30 days, all-cause rehospitalization occurred in 13.6% of patients receiving combination therapy compared with 16.9% in the comparator group, yielding an odds ratio of 0.77, with a 95% CI of 0.62 to 0.95 and p = 0.014. Atrial fibrillation-related rehospitalization was significantly lower in the combination group, at 5.1% versus 7.4%, with an odds ratio of 0.67 and p = 0.008. Rhythm-related urgent visits occurred in 3.6% versus 5.4%, with an odds ratio of 0.65 and p = 0.019. No significant difference in 30-day mortality was observed, at 0.9% versus 1.2%, with p = 0.40. Safety analysis demonstrated a higher rate of bradycardia- or hypotension-related encounters in the combination group, at 2.7% versus 1.5%, with an odds ratio of 1.83 and p = 0.038, without differences in pacemaker implantation. Conclusion Among patients hospitalized with AF, discharge on amiodarone plus beta-blocker therapy was associated with a modest reduction in 30-day rehospitalization, driven primarily by fewer rhythm-related events, with a small increase in bradycardia-related complications. These findings support a selective rhythm-control strategy in appropriately chosen patients.