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

Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon complication of acute pulmonary embolism (PE), resulting in elevated pulmonary pressure and higher risk of PE recurrence. Therefore, lifelong anticoagulant therapy is mandatory in patients diagnosed with this condition. Despite anticoagulation with vitamin K antagonists (VKAs) has always represented the standard of care in this setting, the spread of direct oral anticoagulants (DOACs) raised the question of the potential applicability of their use also in CTEPH. We performed a systematic review and meta-analysis of randomized and observational studies focusing on patients with CTEPH treated with either VKAs or DOACs. Key clinical outcomes as venous thromboembolism (VTE) recurrence, bleedings (major bleeding, clinically relevant non-major bleeding, and intracranial hemorrhage), and mortality were evaluated. Overall, 12 studies including 4071 patients were selected in the quantitative analysis, 10 had an observational design. We found no difference between DOACs and VKAs for VTE recurrence (RR 0.99, 95% CI 0.40–2.43), overall bleedings (RR 0.77, 95% CI 0.45–1.32), and all-cause death (RR 0.58, 95% CI 0.30–1.14). These results were consistent for the aforementioned outcomes also in a sensitivity analysis pooling the results of RCTs and prospective studies only (OR 0.75, 95% CI 0.24–2.38; OR 0.59, 95% CI 0.22–1.56; OR 0.69, 95% CI 0.01–74.68; respectively). DOACs appear to be as effective and safe as VKAs for patients with CTEPH, therefore their use may be considered in the absence of clinical contraindications. Larger randomized controlled trials are warranted to further confirm our findings.