Virginie Dufrost1, Jessie Risse1, Tatiana Reshetnyak2, Maria Satybaldyeva2, Yao Du3, Xin-Xin Yan3, Stella Salta4, Grigorios Gerotziafas4, Zhi-Cheng Jing3, Ismaël Elalamy4, Denis Wahl1, Stéphane Zuily5. 1. University of Lorraine, Inserm UMR_S 1116, CHRU de Nancy, Vascular Medicine Division and Regional Competence Center For Rare Vascular And Systemic Autoimmune Diseases, Nancy, France. 2. Laboratory of Vascular Rheumatology, V.A. Nasonova Research Institute of Rheumatology, 115522, Kashirskoye Shosse 34a, Moscow, Russia. 3. The Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China. 4. Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, Institut National de la Santé et de la Recherche Médicale (INSERM) U938 and Institut Universitaire de Cancérologie, Faculté de Médecine, Sorbonne Université, Paris, France; Service d'Hématologie Biologique Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France. 5. University of Lorraine, Inserm UMR_S 1116, CHRU de Nancy, Vascular Medicine Division and Regional Competence Center For Rare Vascular And Systemic Autoimmune Diseases, Nancy, France. Electronic address: s.zuily@chru-nancy.fr.
Abstract
BACKGROUND: Direct oral anticoagulants (DOACs) are widely used for secondary prevention of venous thromboembolism (VTE) but their clinical efficacy and safety are not established in Antiphospholipid Syndrome (APS) patients. There is only one randomized controlled trial published while others are still ongoing. Many non-randomized studies have been published in this field with conflicting opinions. PURPOSE OF REVIEW: We conducted a systematic review using MEDLINE, EMBASE and Cochrane databases from 2000 until March 2018 regarding APS patients treated with DOACs. We performed a patient-level data meta-analysis to a) estimate the prevalence of recurrent thrombosis in APS patients treated with DOACs in the literature, and b) identify variables associated with recurrent thrombosis. RESULTS: We identified 47 studies corresponding to 447 APS patients treated with DOACs. Three commercially available DOACs were analyzed: rivaroxaban (n = 290), dabigatran etexilate (n = 144) and apixaban (n = 13). A total of 73 out of 447 patients (16%) experienced a recurrent thrombosis while on DOACs with a mean duration until thrombosis of 12.5 months. Rates of recurrent thromboses were 16.9% and 15% in APS patients receiving either anti-Xa inhibitors or dabigatran respectively. Triple positivity (positivity for all three antiphospholipid antibodies) was associated with a four-fold increased risk of recurrent thrombosis (56% vs 23%; OR = 4.3 [95%CI; 2.3-7.7], p < 0.0001) as well as a higher number of clinical criteria for APS classification. In patients treated with anti-Xa inhibitors, history of arterial thrombosis was associated with a higher risk of recurrent thrombosis (32% vs 14%; OR = 2.8 [95%CI; 1.4-5.7], p = 0.006). In conclusion, DOACs are not effective in all APS patients and should not be used routinely in these patients. Randomized controlled trials assessing clinical efficacy and safety as primary endpoints are underway. In the meantime, a registry of APS patients on DOACs could be proposed to establish in which APS subgroups DOACs would be a safe alternative to warfarin.
BACKGROUND: Direct oral anticoagulants (DOACs) are widely used for secondary prevention of venous thromboembolism (VTE) but their clinical efficacy and safety are not established in Antiphospholipid Syndrome (APS) patients. There is only one randomized controlled trial published while others are still ongoing. Many non-randomized studies have been published in this field with conflicting opinions. PURPOSE OF REVIEW: We conducted a systematic review using MEDLINE, EMBASE and Cochrane databases from 2000 until March 2018 regarding APSpatients treated with DOACs. We performed a patient-level data meta-analysis to a) estimate the prevalence of recurrent thrombosis in APSpatients treated with DOACs in the literature, and b) identify variables associated with recurrent thrombosis. RESULTS: We identified 47 studies corresponding to 447 APSpatients treated with DOACs. Three commercially available DOACs were analyzed: rivaroxaban (n = 290), dabigatran etexilate (n = 144) and apixaban (n = 13). A total of 73 out of 447 patients (16%) experienced a recurrent thrombosis while on DOACs with a mean duration until thrombosis of 12.5 months. Rates of recurrent thromboses were 16.9% and 15% in APSpatients receiving either anti-Xa inhibitors or dabigatran respectively. Triple positivity (positivity for all three antiphospholipid antibodies) was associated with a four-fold increased risk of recurrent thrombosis (56% vs 23%; OR = 4.3 [95%CI; 2.3-7.7], p < 0.0001) as well as a higher number of clinical criteria for APS classification. In patients treated with anti-Xa inhibitors, history of arterial thrombosis was associated with a higher risk of recurrent thrombosis (32% vs 14%; OR = 2.8 [95%CI; 1.4-5.7], p = 0.006). In conclusion, DOACs are not effective in all APSpatients and should not be used routinely in these patients. Randomized controlled trials assessing clinical efficacy and safety as primary endpoints are underway. In the meantime, a registry of APSpatients on DOACs could be proposed to establish in which APS subgroups DOACs would be a safe alternative to warfarin.
Authors: Austin A Robinson; Cory R Trankle; Grayson Eubanks; Christopher Schumann; Paul Thompson; Ryan L Wallace; Shouri Gottiparthi; Benjamin Ruth; Christopher M Kramer; Michael Salerno; Kenneth C Bilchick; Cody Deen; Michael C Kontos; John Dent Journal: JAMA Cardiol Date: 2020-06-01 Impact factor: 14.676
Authors: Diego Chemello; Larissa Rosa; Amanda Faria de Araujo; Pedro Cargnelutti de Araujo; Luiz Carlos Carneiro Pereira; Suélen Feijó Hillesheim; Marco Aurélio Lumertz Saffi Journal: J Vasc Bras Date: 2021-04-28