Long-term real-world effectiveness and safety of edoxaban in chronic thromboembolic pulmonary hypertension: a nationwide registry study

BACKGROUND Long-term real-world outcomes of edoxaban in chronic thromboembolic pulmonary hypertension (CTEPH) remain incompletely characterised despite emerging evidence, including the KABUKI randomised trial. OBJECTIVES To evaluate long-term effectiveness and safety of edoxaban in patients with CTEPH using a nationwide registry. METHODS We analysed the CTEPH AC Registry, a multicentre prospective observational cohort. Patients with CTEPH receiving edoxaban at registration were included. The primary effectiveness endpoint was morbidity and mortality events, a composite of all-cause death, lung transplantation, rescue pulmonary endarterectomy or balloon pulmonary angioplasty, ≥15% decline in 6-minute walk distance with worsening World Health Organization (WHO) functional class, or symptomatic venous thromboembolism. The primary safety endpoint was clinically relevant bleeding according to International Society on Thrombosis and Haemostasis criteria. RESULTS Among 408 patients, median follow-up was 552 days. The cumulative incidence of morbidity and mortality events was 4.7%, 10.0%, and 14.1% at 1, 3, and 5 years, respectively. The cumulative incidence of clinically relevant bleeding was 3.2%, 4.8%, and 5.6%, respectively, and major bleeding occurred in 2.4% at 5 years. Symptomatic venous thromboembolism occurred in 1.5% at 5 years. Outcomes were broadly consistent across reperfusion history, WHO functional class, edoxaban dose, and renal function strata. CONCLUSIONS In this Japanese nationwide registry, long-term edoxaban therapy was associated with sustained clinical stability in patients with CTEPH. No clear late-emerging safety signal was observed, but extrapolation beyond Japan requires caution, particularly in patients with different body size, renal function, or concomitant medication profiles.