Long-term outcomes of direct oral anticoagulants versus warfarin for chronic thromboembolic pulmonary hypertension: a reconstructed individual patient data meta-analysis

Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is a subtype of pulmonary hypertension that can be managed with surgical intervention or lifelong anticoagulation. Vitamin K antagonists are the first line anticoagulants but direct oral anticoagulants (DOACs) have become increasingly popular due to their effectiveness and favourable safety profile. Purpose This meta-analysis evaluates the efficacy of warfarin versus DOACs in the treatment of CTEPH. Methods A systematic literature search was conducted in PubMed, EMBASE, and Web of Science up to December 31, 2024. Individual patient data were reconstructed from published Kaplan-Meier (KM) curves. The meta-analysis assessed survival, recurrence of venous thromboembolism, and bleeding risk. Outcomes were measured using a random-effects hazard ratio model. Statistical analyses were conducted using R. Results Five studies with published KM curves, including a total of 3,645 patients (1,225 patients on DOACs and 2,420 patients on warfarin), were included in this meta-analysis. The total follow-up duration was approximately 4,585 days. The survival was significantly higher in patients treated with DOACs compared to those receiving warfarin (HR: 1.64, 95% CI: 1.26–2.14). However, the recurrence rate of venous thromboembolism was similar between warfarin and DOACs (HR: 1.32, 95% CI: 0.83–2.09). Additionally, the risk of bleeding was higher in patients treated with warfarin than in those receiving DOACs (HR: 1.77, 95% CI: 1.23–2.55). Conclusion DOACs demonstrate superiority over warfarin in terms of mortality and safety. Therefore, DOACs represent a better and safer alternative to warfarin for treating CTEPH.