Utilization and safety of digoxin in patients with chronic heart failure and atrial fibrillation with rapid ventricular rate

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Abstract Background Digoxin can reduce symptoms and the risk of tachycardia-induced cardiomyopathy in patients with heart failure (HF) and concomitant atrial fibrillation (AF) with rapid ventricular rate. The effect of digoxin in HF and AF has not been tested in randomized controlled trials, and observational data have shown conflicting results linking digoxin to increased mortality in AF, though the nature of observational data makes it prone to bias and results difficult to interpret. Purpose To assess the utilization of digoxin in patients with HF and AF, and its association with New York Heart Association (NYHA) functional class and survival. Methods We used data from the Norwegian HF registry that collected data from all Norwegian HF clinics between 2013-2022. Data was collected from the first and last visit during optimizization of HF medical therapy. Associations with mortality status from Statistics Norway were assessed in unadjusted time-to-event analysis, and after adjustment for age, sex, body mass index, estimated glomerular filtration rate, aldosterone antagonists, renin-angiotensin-aldosterone system inhibitors, and beta blockers. Results The study included 4,877 HF patients, consisting of 4,067 (83.4%) with ejection fraction (EF) ≤40% and 810 (16.6%) with EF >40%.. The mean age was 67.7±12.0 years; 25.1% were women, and 27.3% had NYHA functional class III/IV. At the first visit, 1,339 (27.5%) patients had AF and 829 (61.9%) of these were treated with ≥50% of the beta-blocker target dose. AF with a ventricular rate ≥100 bpm was present in 277 (20.1%) patients, and 188 (67.9%) of these were on ≥50% beta-blocker target dose. Similarly, 262 (19.6%) of all AF patients and 44 (15.9%) of those with a ventricular rate ≥100 bpm were treated with digoxin. After optimization of HF medical therapy (median duration 140 [Q1–Q3 82–237] days), 1,039 (21.3%) patients had AF. Among these, 227 (21.9%) were treated with digoxin, including 9 (18.0%) patients with ventricular rate ≥100 bpm. Patients with AF who were started on digoxin experienced during the optimization period a larger decline in heart rate compared to those who were not (mean change -23.7±17.2 vs. -5.7±16.7 bpm, p=0.001), and more often an improvement in NYHA functional class (45% vs 30%, p=0.018). During median 779 [Q1–Q3 386–1,334)] days of follow-up after the last optimization visit, digoxin use was associated with lower mortality in HF patients with AF in unadjusted analysis (HR 0.67 [0.46–0.97]). After adjustment for baseline characteristics and other HF medical therapies, the association with mortality was attenuated and no longer significant (HR 0.96 [0.65–1.42]). Conclusion Digoxin was infrequently used in patients with HF and AF with rapid ventricular rate but was associated with a greater decrease in heart rate and improvement in NYHA functional class. The use of digoxin appears safe and was not associated with increased mortality.