Gabriel Laurence, Delavenne Xavier, Bedouch Pierrick, Khouatra Chahéra, Bouvaist Hélène, Cordier Jean-François, Mornex Jean-François, Pison Christophe, Cottin Vincent, Bertoletti Laurent
Laboratoire de Pharmacologie, Toxicologie et Gaz du Sang, CHU Saint-Etienne, Saint-Etienne, France.
Respiration. 2016;91(4):307-15. doi: 10.1159/000445122. Epub 2016 Apr 16.
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.
We aimed to evaluate the frequency of bioaccumulation risks in patients treated with PAH-targeted therapy, particularly regarding the presence of validated indications.
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).
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.
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.
接受肺动脉高压(PAH)治疗的患者经常因PAH或已证实的适应症(如心房颤动或静脉血栓栓塞)而接受维生素K拮抗剂(VKA)治疗。在这些后者的适应症中,VKA受到直接口服抗凝剂(DOA)的挑战。有人提出在有生物蓄积风险的患者中减少DOA的剂量。
我们旨在评估接受PAH靶向治疗的患者中生物蓄积风险的频率,特别是关于已证实适应症的存在情况。
我们在三个不同的PAH转诊中心进行了一项回顾性研究。所有接受PAH靶向治疗的患者根据人口统计学、VKA的处方和适应症以及主要生物蓄积风险因素(肾衰竭、低体重、强效P-糖蛋白或细胞色素P3A4抑制剂)的存在情况进行分类。
纳入的366例患者中有239例接受了VKA治疗,其中94例有已证实的适应症。在整个研究人群中,231例(63.1%)至少有一个主要风险因素,在因已证实适应症接受抗凝治疗的患者中,54例(57.4%)至少有一个主要风险因素。没有特定的患者表型可以个体化。
接受PAH治疗的患者中约有二分之一至少有DOA生物蓄积的三个主要风险因素之一。在PAH背景下,DOA可能与生物蓄积有关,应个体化给药,主要是在有确诊适应症的患者中。