Direct oral anticoagulants for the treatment and prevention of venous thromboembolism in patients with cancer: current e
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REVIEW ARTICLE
Direct oral anticoagulants for the treatment and prevention of venous thromboembolism in patients with cancer: current evidence I. García‑Escobar1 · E. Brozos‑Vázquez2 · D. Gutierrez Abad3 · V. Martínez‑Marín4 · V. Pachón5 · A. J. Muñoz Martín6 · Cancer and Thrombosis Section of the Spanish Society of Medical Oncology (SEOM) Received: 8 May 2020 / Accepted: 28 September 2020 © The Author(s) 2020
Abstract Venous thromboembolic disease (VTED) is a common and clinically important complication in patients with cancer, contributing to its mortality and morbidity. Direct oral anticoagulant agents (DOACs), including direct thrombin inhibitors and direct factor Xa inhibitors, are as effective as vitamin K antagonists for the treatment of VTED and are associated with less frequent and severe bleeding. They have advantages over low-molecular-weight heparin, but comparative long-term efficacy and safety data are lacking for these compounds. Recent randomized clinical trials suggest a role for DOACs in the treatment of VTED in patients with cancer. This review will discuss the existing evidence and future perspectives on the role of DOACs in the treatment of VTE based on the current evidence about their overall efficacy and safety and the limited information in patients with cancer; in addition, we will briefly review their pharmacokinetic properties with special reference to potential interactions. Keywords Venous thromboembolic disease · Cancer · Direct oral anticoagulant agents · Efficacy · Safety
Introduction Venous thromboembolic disease (VTED) is a common and clinically important complication in patients with cancer [1]. Coagulation and cancer interact bidirectionally in a vicious circle in which the tumor is able to activate coagulation by * I. García‑Escobar [email protected] 1
Servicio de Oncología, Hospital General Universitario de Ciudad Real, Calle Obispo Rafael Torija, s/n, 13005 Ciudad Real, Spain
2
Servicio de Oncología Médica, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain
3
Servicio de Oncología, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain
4
Servicio de Oncología Médica, Hospital Universitario La Paz, Madrid, Spain
5
Servicio de Oncología Médica, Hospital Universitario Ramon Y Cajal, IRYCIS, CIBERONC, Madrid, Spain
6
Servicio de Oncología Médica, Hospital General Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain
producing procoagulant factors (e.g., tissue factors, cancer procoagulant proteins, microparticles, molecules of adhesion, proangiogenic factors and cytokines); these factors promote the generation of thrombin and the formation of fibrin which, in turn, favor the progression and growth of the tumor [2]. In cancer patients, factors that may be related to the increased risk of VTED could be patient-related (age, sex, race, comorbidities, immobilization, and previous history of thrombosis), cancer-related (tumor location, tumor stage, histology, and time from diagnosis) and treatment-
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