Digoxin use and outcomes in contemporary heart failure: a propensity score-weighted real-world analysis

<title>Abstract</title> <p> Background and objectives: The role of digoxin in heart failure (HF) has been reconsidered following recent evidence suggesting potential benefits when used alongside contemporary guideline-directed medical therapy. The aim was to describe the clinical characteristics of patients receiving digoxin and to evaluate the association between digoxin treatment and one-year clinical outcomes using propensity score-based methods to account for treatment-selection bias. Methods A retrospective single-center study including 572 patients admitted for acute decompensated HF to an Internal Medicine Department between 2013 and 2025 Patients were stratified according to digoxin prescription at discharge. The primary endpoint was the composite of all-cause mortality or HF rehospitalization within 365 days. Inverse probability of treatment weighting (IPTW) based on propensity scores was applied to reduce treatment-selection bias, and weighted Cox proportional hazards models were used to assess associations between digoxin use and clinical outcomes. Results Digoxin was prescribed in 109 patients (19.1%). Compared with untreated patients, those receiving digoxin were more frequently women and had a higher prevalence of atrial fibrillation, previous HF, preserved left ventricular ejection fraction (HFpEF), higher CA125 levels, and better renal function. After IPTW adjustment, baseline covariates were well balanced. During one-year follow-up, 278 patients experienced the primary composite endpoint, 157 died, and 187 were rehospitalized for HF. Digoxin treatment was not associated with the composite endpoint (hazard ratio [HR] 1.12, 95% confidence interval [CI] 0.73–1.70; <italic>p</italic>  = 0.61), all-cause mortality (HR 1.58, 95% CI 0.97–2.59; <italic>p</italic>  = 0.067), or HF rehospitalization (HR 0.85, 95% CI 0.50–1.44; <italic>p</italic>  = 0.55). No significant interactions were observed according to atrial fibrillation status or HF phenotype, and findings remained consistent in multivariable sensitivity analyses. Conclusions In this contemporary real-world cohort, digoxin was primarily prescribed to elderly patients with atrial fibrillation and HFpEF. After rigorous adjustment for baseline differences using propensity score weighting, digoxin treatment was not significantly associated with all-cause mortality or HF rehospitalization within 365 days. These findings highlight the importance of accounting for treatment-selection bias in observational studies and provide evidence regarding digoxin use in patient populations underrepresented in randomized clinical trials. </p>