Long-term outcome of chronic thromboembolic pulmonary hypertension using direct oral anticoagulants and warfarin: a Japanese prospective cohort study

Abstract

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) requires lifelong anticoagulation. Long-term outcomes of CTEPH under current anticoagulants are unclear.

Objectives: The CTEPH AC registry is a prospective, nationwide cohort study comparing the safety and effectiveness of direct oral anticoagulants (DOACs) and warfarin for CTEPH.

Patients/methods: Patients with CTEPH, both tre atment-naïve and on treatment, were eligible for the registry. Inclusion criteria were patients aged ≥20 years and those who were diagnosed with CTEPH according to standard guidelines. Exclusion criteria were not specified. The primary efficacy outcome was a composite morbidity, and mortality outcome comprised all-cause death, rescue reperfusion therapy, initiation of parenteral pulmonary vasodilators, and worsened 6-minute walk distance and WHO functional class. The safety outcome was clinically relevant bleeding, including major bleeding.

Results: Nine hundred twenty-seven patients on oral anticoagulants at baseline were analyzed: 481 (52%) used DOACs and 446 (48%) used warfarin. The 1-, 2-, and 3-year rates of composite morbidity and mortality outcome were comparable between the DOAC and warfarin groups (2.6%, 3.1%, and 4.2% vs 3.0%, 4.8%, and 5.9%, respectively; P = .52). The 1-, 2-, and 3-year rates of clinically relevant bleeding were significantly lower in DOACs than in the warfarin group (0.8%, 2.4%, and 2.4% vs 2.5%, 4.8%, and 6.4%, respectively; P = 0.036). Multivariable Cox proportional-hazards regression models revealed lower risk of clinically relevant bleeding in the DOAC group than the warfarin group (hazard ratio: 0.35; 95% CI: 0.13-0.91; P = .032).

Conclusion: This registry demonstrated that under current standard of care, morbidity and mortality events were effectively prevented regardless of anticoagulants, while the clinically relevant bleeding rate was lower when using DOACs compared with warfarin.

Keywords: anticoagulants; hypertension; observational study; pulmonary; registries; venous thromboembolism.