Background: Digoxin increases cardiac output modestly in acute settings in patients with pulmonary arterial hypertension (PAH) and right ventricular failure; however, very little is known about the effects of chronic digoxin therapy in PAH.
Methods: We studied 251 patients with PAH from the Minnesota Pulmonary Hypertension Repository, a prospective registry that enrolls all consecutive patients treated at the University of Minnesota. Person-time began at the date of PAH diagnosis. Date of digoxin prescription was recorded. Primary endpoint was all-cause mortality. Mortality hazard ratios (HRs) were calculated using Cox proportional hazards regression, with digoxin use as a time-dependent covariate, adjusted for baseline patient characteristics.
Results: The mean age was 55 ± 15 years, and 73% were women. 67 Sixty-seven (27%) patients were treated with digoxin. When compared to with those who were not treated with digoxin, patients on digoxin were more likely to be younger (52 vs. 56 years; P = p=0.07), had idiopathic PAH (28% vs. 17%; P = p=0.06), on warfarin therapy (22% vs. 13%; pP = 0.07) and had worse hemodynamics: higher right atrial pressure (11mmHg vs. 8 mmHg; P < p<0.001), higher mean pulmonary artery pressure (51mmHg vs. 44 mmHg; P = p=0.001), higher pulmonary vascular resistance (11.1 WU vs. 7.7 WU; P < p<0.001) and lower cardiac index (2.0L/min/m2 vs. 2.6 L/min/m2). During a median follow-up time of 4.5 years, there were a total of 95 deaths (27 in digoxin group vs. 68 in no digoxin group). Digoxin use was associated with higher mortality both with and without adjusting for the baseline characteristics [Crude crude HR 1.83 (95%CIconfidence interval: 1.17 – –2.86); Adjusted HR 2.26 (95% confidence intervalCI: 1.36 – –3.76)].
Conclusion: Digoxin is used more often in patients with severe idiopathic PAH and is associated with increased mortality even after adjusting for the severity of PAH and right heart failure. Future prospective studies should assess the safety/efficacy of chronic digoxin use in PAH.
KEY CONTRIBUTORS
Kevin Y. Chang, Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN, USA Katherine Giorgio, Rob F. Walker, Pamela L. Lutsey, Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA Kurt W. Prins, Marc Pritzker, Thenappan Thenappan, Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, MN, USA
