Anticoagulation in chronic thromboembolic pulmonary hypertension: A systematic review and meta-analysis

Introduction: Life-long anticoagulation is the recommended management for chronic thromboembolic pulmonary hypertension (CTEPH). Evidence regarding the use of direct oral anticoagulants (DOAC) for CTEPH is yet to be established. We performed a systematic review and meta-analysis to clarify the outcomes of CTEPH in patients who used DOAC or vitamin K antagonists (VKA). Methods: We reviewed literature in PubMed and EMBASE through March 2023. We included studies involving patients with CTEPH where DOAC and VKA were compared. We collected data including intervention history for CTEPH, bleeding events, recurrence of VTE (venous thromboembolism), and mortality. We performed a metaanalysis using the Mantel-Haenszel method with a fixed-effects model.Results: We included one randomized clinical trial and six observational studies, with a total of 2969 patients. Six studies investigated major bleeding outcomes, and seven investigated all bleeding outcomes. There were no differences in major bleeding (RR 0.59, 95 % CI [0.34-1.02], I2 = 0 %) and all-bleeding (RR 0.87, 95 % CI [0.67-1.13], I2 = 0 %). Based on the five studies we included, DOAC was associated with a lower risk of mortality (RR 0.54, 95 % CI: 0.37-0.79, I2 = 5 %). However, a higher risk of recurrent pulmonary embolism (PE) was seen in three studies (RR 3.80, 95 % CI: [1.93-7.50], I2 = 11 %). No significant differences were noted in terms of VTE.Conclusion: DOAC compared to VKA was associated with a significantly lower mortality and higher risk of recurrent PE. Since most of the included studies are observational, we must consider the existence of multiple biases and confounding factors.