title: Risk of Direct Oral Anticoagulant Bioaccumulation in Patients with Pulmonary Hypertension.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Laboratoire de Pharmacologie, Toxicologie et Gaz du Sang, CHU Saint-Etienne, Saint-Etienne, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Gabriel
authors.forename: Xavier
authors.initials: X
authors.lastname: Delavenne
authors.forename: Pierrick
authors.initials: P
authors.lastname: Bedouch
authors.forename: Chahéra
authors.initials: C
authors.lastname: Khouatra
authors.forename: Hélène
authors.initials: H
authors.lastname: Bouvaist
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Cordier
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Mornex
authors.forename: Christophe
authors.initials: C
authors.lastname: Pison
authors.forename: Vincent
authors.initials: V
authors.lastname: Cottin
authors.forename: Laurent
authors.initials: L
authors.lastname: Bertoletti
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D003404:Creatinine