Beta blockers, digoxin or both following an incident diagnosis of atrial fibrillation; a prospective cohort study

Abstract

Background: Atrial fibrillation is one of the most common arrhythmias but the optimal drug choice for a rate control strategy remains uncertain. In particular, controversy and uncertainty exists regarding the safety of digoxin in this context. Methods: This was a retrospective cohort claims database study of patients with an incident hospital discharge diagnosis of atrial fibrillation between 2011 and 2015. The exposure variables were a discharge prescription for beta blockers, digoxin or both. The primary outcome was a composite of total in-hospital mortality or a repeat cardiovascular (CV) hospitalization. Secondary outcomes were the individual components of the primary outcome. Baseline confounding was controlled with propensity score inverse probability weighting using a entropy balancing algorithm and the prespecified estimand was the average treatment effect among the treated. In sensitivity analyses, baseline covariate imbalances were adjusted using a maximum likelihood algorithm and an overall average treatment effect estimand. Treatment effects for the weighted samples were calculated from a Cox proportional hazards model. Results: 12,723 patients were discharged on beta blockers alone, 406 on digoxin alone, and 1,499 discharged on combined beta blocker / digoxin therapy with a median follow-up time of 356 days. In the unadjusted analyses, the primary outcome occured most frequently in the combined exposure group (15.5%) compared to the isolated digoxin (13.3%) and beta blocker (11.5%) groups (p < 0.001 for trend). There were more CV hospitalizations in the combined beta blocker / digoxin group (14.4%) compared to the BB (10.7%) or digoxin (10.6%) groups (p = 0.006 for trend). There were more deaths in the digoxin group (2.7%) and the combined group (1.1%) groups compared to the BB alone group (0.8%) (p < 0.001 for trend). However, after baseline covariate adjustment, the digoxin alone (hazard ratio (HR) 1.24, 95% CI 0.85 - 1.81) and the combined group (HR 1.09, 95% CI 0.90 - 1.31) were not associated with increased risk for the composite endpoint compared with the beta blocker alone group. These results were robust to sensitivity analyses. Conclusion: After accounting for baseline imbalances, patients hospitalized for incident atrial fibrillation and discharged on digoxin alone or the combination of digoxin and a beta blocker were not associated with an increase in the composite outcome of recurrent CV hospitalizations and death compared to those discharged on isolated beta blocker therapy. However, additional studies are required to refine the precision of these estimates.