Cost-effectiveness of digitoxin in heart failure with reduced ejection fraction in the European Union and the United States

AIMS: Digitoxin reduced the composite of death or worsening heart failure in DIGIT-HF, but whether these benefits translate into economic value remains unknown. We assessed its cost-effectiveness as add-on therapy for heart failure with reduced ejection fraction (HFrEF) across all 27 European Union Member States (EU-27) and the United States (US). METHODS: We developed a DIGIT-HF-informed, multi-jurisdictional three-state Markov cost-utility model projecting 10-year and lifetime outcomes. Clinical risks and intention-to-treat effects were held constant; hospitalization costs, EQ-5D-5L utilities, digitoxin costs, discounting, and willingness-to-pay (WTP) thresholds varied by jurisdiction. Uncertainty was assessed using 10 000 probabilistic simulations. RESULTS: Across the EU-27, digitoxin was cost-effective at 10 years, with incremental costs of -€338 to +€25 per patient, incremental quality-adjusted life-years (QALYs) of 0.188-0.231, and a maximum incremental cost-effectiveness ratio (ICER) of €120/QALY. Over lifetime, corresponding ranges were -€79 to +€72, 0.373-0.453 QALYs, and a maximum ICER of €174/QALY. At €50 000/QALY, cost-effectiveness probability was 92%. Digitoxin was cost-saving in 24 of 27 Member States at 10 years and 10 of 27 over lifetime. In the USA, it was cost-saving (lifetime savings US$405 per patient; 0.43 QALYs; 93.4% probability of cost-effectiveness). CONCLUSION: Digitoxin generated clinically meaningful health benefits at negligible incremental cost and remained cost-effective across every evaluated EU-27 healthcare system and the USA. Economic value emerged earliest within the first decade and in higher-cost hospital systems, while lifetime analysis captured larger cumulative gains in quality-adjusted survival.