POLSKIE ARCHIWUM MEDYCYNY WEWNĘTRZNEJ 2016; 126 (9) 1 can lead to venous ulcers in severe cases. 7 Chron- ic thromboembolic pulmonary hypertension oc- curs in 2% to 4% of patients with PE and can be fatal. 8 Terefore, VTE is a common disorder asso- ciated with signifcant morbidity and mortality. Anticoagulants are the cornerstone of VTE treatment. Te goal of therapy is to prevent thrombus extension or embolization, and to pre- vent new thrombi from forming. Conventional treatment starts with a rapidly acting parenteral anticoagulant, usually low-molecular-weight hep- arin (LMWH), which is overlapped with a vitamin K antagonist (VKA), such as warfarin. Te paren- teral anticoagulant is given for at least 5 days and is stopped when a therapeutic response to warfa- rin has been achieved as evidenced by an interna- tional normalized ratio (INR) between 2 and 3. Warfarin is then continued as long-term thera- py for a minimum of 3 months. At this point, the decision to stop or continue treatment depends on the balance between the risk of recurrence if Introduction Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common condition that occurs for the frst time in about 1 in 1000 persons each year and the incidence rises with age. 1,2 About one-third of patients with symp- tomatic VTE present with PE, while the remain- der manifest as DVT. 3 Within 1 month of diagno- sis, death occurs in approximately 6% of patients with DVT and 12% of those with PE. 4 Although VTE often occurs after surgery, with immobiliza- tion, or in patients with cancer, up to 50% of pa- tients with VTE have no identifable risk factors and are classifed as having unprovoked VTE. 5 If anticoagulant therapy is stopped in patients with unprovoked VTE, the risk of recurrence is about 10% at 1 year and 30% at 5 years. 6 Recur- rent DVT in the ipsilateral leg increases the risk of postthrombotic syndrome, a chronic disor- der characterized by leg swelling and discomfort that occurs in 20% to 50% of DVT patients and Correspondence to: Jeffrey I. Weitz, MD, Thrombosis and Atherosclerosis Research Institute, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada, phone: +1 905 574 8550, e-mail: weitzj@taari.ca Received: September 4, 2016. Accepted: September 4, 2016. Published online: September 5, 2016. Conflict of interests: JIW reports research support from Canadian Institutes of Health Research, Heart and Stroke Foundation, and Canadian Foundation for Innovation and consulting fees from Bristol‑Myers Squibb, Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Bayer, Janssen Pharmaceuticals, Portola, IONIS Pharmaceuticals, and Merck. IHJ has research support from CCS‑Bayer Vascular Resident Award and Boehringer Ingelheim. Pol Arch Med Wewn. 2016; 126 (9): 688-696 doi:10.20452/pamw.3547 Copyright by Medycyna Praktyczna, Kraków 2016 Key words bleeding risk, direct oral anticoagulants, periprocedural management, venous thromboembolism AbstrAct Direct oral anticoagulants (DOACs) are rapidly replacing vitamin K antagonists (VKAs) for treatment of venous thromboembolism (VTE). The DOACs include dabigatran, which inhibits thrombin, and rivaroxa‑ ban, apixaban, and edoxaban, which inhibit factor Xa. When compared with conventional VTE treat ‑ ment consisting of a parenteral anticoagulant followed by a VKA, the DOACs were equally effective for prevention of recurrence, but were associated with less bleeding. With similar efficacy, better safety, and the convenience of fixed dosing without the need for routine coagulation monitoring, guidelines now recommend DOACs over VKAs for VTE treatment in patients without active cancer. Nonetheless, measures are needed to optimize the safety of DOACs. Focusing on these measures, this paper summarizes the results of phase III trials evaluating DOACs for VTE treatment; identifies which VTE patients are or are not candidates for DOACs; provides guidance on how to choose among DOACs; lists the licensed dos‑ ing information for DOACs; discusses the optimal treatment duration for VTE; describes periprocedural management of DOACs in patients requiring surgery or intervention; and finally, reviews the management of bleeding, including the role for specific reversal agents. reVIew ArtIcLe Optimizing the safety of treatment for venous thromboembolism in the era of direct oral anticoagulants Jefrey I. Weitz 1,2 , Iqbal H. Jafer 3 1 Department of Medicine, McMaster University, Hamilton, Canada; Thrombosis and Atherosclerosis Research Institute, Hamilton, Canada 2 Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada 3 Department of Surgery, McMaster University, Hamilton, Canada; Thrombosis and Atherosclerosis Research Institute, Hamilton, Canada