Direct oral anticoagulants versus vitamin K antagonists after pulmonary endarterectomy: a systematic review and meta-analysis

Patients with chronic thromboembolic pulmonary hypertension who undergo pulmonary endarterectomy (PEA) require lifelong anticoagulation, yet the optimal regimen after surgery remains uncertain. Although vitamin K antagonists (VKAs) are traditionally used, direct oral anticoagulants (DOACs) have gained attention as potentially safer and more convenient alternatives. This systematic review and meta-analysis aims to evaluate the efficacy and safety of DOACs compared with VKAs in the post-PEA population. We systematically searched three English and four Chinese databases for relevant studies published up to March 2025. Risk of bias was evaluated using RoB 2 for RCTs and ROBINS-I for observational studies. Outcomes included venous thromboembolism (VTE), pulmonary embolism (PE) recurrence, bleeding events, and all-cause mortality. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Five studies (one randomized trial and four observational studies) involving 1986 patients were included. Overall, DOACs did not increase the risk of VTE recurrence compared with VKAs, but were associated with a higher likelihood of PE recurrence (RR = 2.99; 95% CI 1.51–5.93; I 2 = 0%). At the same time, patients receiving DOACs experienced fewer major bleeding events (RR = 0.58; 95% CI 0.37–0.91; I 2 = 0%) and lower all-cause mortality (RR = 0.51; 95% CI 0.35–0.75; I 2 = 0%). Further analyses indicated no significant differences across outcomes in the rivaroxaban-only subgroup, whereas mixed-DOAC regimens were associated with significantly higher risks of both VTE and PE. In patients after PEA, DOACs were associated with lower risks of major bleeding and all-cause mortality, but may be less effective than VKAs in preventing PE recurrence. The current evidence—derived largely from observational studies and of low to very low certainty—does not support routine substitution of VKAs with DOACs in this setting. Clinical equipoise therefore remains, and further research is needed to clarify the optimal regimen. PROSPERO CRD420251008768