Indications and potential pitfalls of anticoagulants in pulmonary hypertension: Would DOACs become a better option than VKAs?

Pulmonary hypertension (PH) comprises a cluster of severe conditions characterized by elevated mean pulmonary arterial pressure. While targeted therapies have been approved over the last twenty years for pulmonary arterial hypertension (PAH) and chronic-thrombo-embolic PH (CTEPH), the possible role of anticoagulant therapy as a supportive treatment PAH is still debated. In PAH, anticoagulant use remains frequent, although evidence appear to be poor (recommendation class IIb-C in international guidelines). In CTEPH treatment, anticoagulants are highly recommended, because it often involves thrombosis (recommendation class I-C in international guidelines). Historically, PH patients have been treated with vitamin K antagonists (VKA), which are the only available oral anticoagulants. In this context, risk/benefit ratio of VKA is affected by the risk of major bleeding events. This drawback could be mitigated with direct oral anticoagulants (DOACs): in addition to being less constraining for patients, DOACs have shown a lower risk of major bleeding events in their already approved indications (venous thromboembolism, atrial fibrillation). However, DOACs have never been specifically assessed in PAH and CTEPH patients. Bioaccumulation risk should be considered if DOACs are prescribed in PAH and CTEPH patients, especially the risk of drug-drug interaction mediated by P-glycoprotein and cytochrome 3A4 with targeted therapies.