Impact of digoxin versus beta-blocker in patients with coexistent atrial fibrillation and heart failure: a target trial emulation

BACKGROUND: This study aimed to compare the impact of digoxin versus beta-blocker on adverse clinical outcomes in patients with coexisting atrial fibrillation (AF) and heart failure (HF). METHODS: This study employed a target trial emulation with a clone-censor-weight approach to analyze data from 28,377 patients diagnosed with both AF and HF in the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong between January 1, 2005, and December 31, 2017. Patients were followed up for up to 3 years or until the occurrence of clinical outcomes. The exposures were digoxin (N = 5351) versus beta-blocker (N = 7655) within a 90-day grace period. Absolute risks (ARs), risk differences, and risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using weighted pooled logistic regression adjusted for demographic characteristics, comorbidities, and medication use. The primary outcome was all-cause mortality, while secondary outcomes included cardiovascular (CV) mortality, heart failure hospitalization, acute ischemic stroke, acute myocardial infarction, and pacemaker implantation. RESULTS: Over 3 years, digoxin was associated with a significantly higher risk of all-cause mortality (AR: 51.2% vs. 42.2%; RR: 1.21; 95% CI: 1.17 to 1.26), CV mortality (AR: 25.1% vs. 21.0%; RR: 1.20; 95% CI: 1.11 to 1.29), and heart failure hospitalization (AR: 29.0% vs. 26.4%; RR: 1.10; 95% CI: 1.04 to 1.16). No significant differences were observed for acute ischemic stroke (AR: 4.3% vs. 4.3%; RR: 1.00; 95% CI: 0.85 to 1.18), acute myocardial infarction (AR: 4.6% vs. 4.3%; RR: 1.04; 95% CI: 0.88 to 1.23), or pacemaker implantation (AR: 1.0% vs. 1.3%; RR: 0.74; 95% CI: 0.54 to 1.01). CONCLUSIONS: In patients with coexisting AF and HF, digoxin was associated with significantly higher risks of all-cause mortality, cardiovascular mortality, and heart failure hospitalization compared to beta-blocker.