Risk of Direct Oral Anticoagulant Bioaccumulation in Patients with Pulmonary Hypertension

Background: Patients treated for pulmonary arterial hypertension (PAH) frequently receive vitamin K antagonists (VKAs) for PAH or validated indications (such as atrial fibrillation or venous thromboembolism). In these latter indications, VKAs are challenged by direct oral anticoagulants (DOAs). Decreased dosage of DOAs has been proposed in patients at risk of bioaccumulation. Objectives: We aimed to evaluate the frequency of bioaccumulation risks in patients treated with PAH-targeted therapy, particularly regarding the presence of validated indications. Methods: We conducted a retrospective study in three different PAH referral centers. All patients receiving PAH-targeted therapy were classified according to demographics, prescription and indications of VKAs, and the presence of major bioaccumulation risk factors (renal failure, low body weight, strong P-glycoprotein or cytochrome P3A4 inhibitors). Results: Two hundred and thirty-nine of the 366 patients included received VKAs, 94 for validated indications. At least one major risk factor was found in 231 (63.1%) of the whole study population, and in 54 (57.4%) of the patients anticoagulated for a validated indication. No specific patient phenotype could be individualized. Conclusions: About 1 in 2 patients treated with PAH therapy has at least one of the three major risk factors for DOA bioaccumulation. DOAs in the PH setting could be associated with bioaccumulation and should be individualized, mainly in patients with confirmed indication. (C) 2016 S. Karger AG, Basel