Effect of Chronic Digoxin Use on Mortality and Heart Failure Hospitalization in Pulmonary Arterial Hypertension

BACKGROUND: Digoxin acutely increases cardiac output in patients with pulmonary arterial hypertension (PAH) and right ventricular failure; however, the effects of chronic digoxin use in PAH are unclear. METHODS AND RESULTS: Data from the Minnesota Pulmonary Hypertension Repository were used. The primary analysis used likelihood of digoxin prescription. The primary end point was a composite of all-cause mortality or heart failure (HF) hospitalization. Secondary end points included all-cause mortality, HF hospitalization, and transplant-free survival. Multivariable Cox proportional hazards analyses determined the hazard ratios (HR) and 95% CIs for the primary and secondary end points. Among 205 patients with PAH in the repository, 32.7% (n=67) were on digoxin. Digoxin was more often prescribed to patients with severe PAH and right ventricular failure. After propensity score-matching, 49 patients were digoxin users, and 70 patients were nonusers; of these 31 (63.3%) in the digoxin group and 41 (58.6%) in nondigoxin group met the primary end point during a median follow-up time of 2.1 (0.6–5.0) years. Digoxin users had a higher combined all-cause mortality or HF hospitalization (HR, 1.82 [95% CI, 1.11–2.99]), all-cause mortality (HR, 1.92 [95% CI, 1.06–3.49]), HF hospitalization (HR, 1.89 [95% CI, 1.07– 3.35]), and worse transplant-free survival (HR, 2.00 [95% CI, 1.12–3.58]) even after adjusting for patient characteristics and severity of PAH and right ventricular failure. CONCLUSIONS: In this retrospective, nonrandomized cohort, digoxin treatment was associated with greater all-cause mortality and HF hospitalization, even after multivariate correction. Future randomized controlled trials should assess the safety and efficacy of chronic digoxin use in PAH.