Sarah Bos

51 Anticoagulant activity of edoxaban in patients with cirrhosis 4 Introduction The liver is the site of synthesis for many proteins involved in hemostasis. Consequently, patients with end-stage chronic liver disease (i.e., cirrhosis) acquire multiple and complex alterations in their hemostatic system. Recent insights in the hemostatic changes in patients with cirrhosis have indicated a balanced, but unstable hemostatic system in these patients with a risk for both bleeding and thrombotic complications including venous thromboembolism (VTE) and portal vein thrombosis.(1,2) Prevention and treatment of thrombotic events are a challenge due to a frequently prolonged baseline international normalized ratio (INR) and substantially decreased levels of antithrombin, impeding correct dosing and monitoring of vitamin K antagonists (VKA) and heparins, respectively. (3,4) There is very limited clinical experience with the new-generation direct oral anticoagulants (DOAC) in patients with cirrhosis, as these patients were excluded from all clinical trials with these new agents. However, DOACs have potential advantages over VKAs and heparins, such as the oral route of administration, the lack of requirement of laboratory monitoring, their mechanism of action, and the wider therapeutic window,(4) which has resulted in increasing interest from the hepatology community. Currently four DOACs are registered in Europe and the US for prevention or treatment of VTE and the prevention of ischemic stroke in patients with non- valvular atrial fibrillation. Edoxaban was found to be non-inferior to warfarin in the prevention of stroke in atrial fibrillation and VTE.(5,6) In addition, edoxaban showed a favourable risk profile with 2.75% incidence of major bleeding compared to 3.43% in patients treated with warfarin.(6) DOACs are contraindicated in patients with advanced liver disease accompanied with coagulopathy and clinically relevant bleeding risk. Nevertheless, a growing number of patients with cirrhosis are treated with these new drugs, despite an absence of clinical information on safety and efficacy. Intagliata et al. were the first to describe their experience with the use of DOACs in patients with cirrhosis. They reported a retrospective cohort in which 20 cirrhotic patients were safely treated with factor Xa inhibitors. The number of bleeding events was similar between patients treated with DOACs or VKAs.(7) A number of studies, including a large study from Taiwan that reported on 1438 patients with cirrhosis treated with a DOAC underline the findings of Intagliata.(8–12) DOACs have been used in attempts to treat portal vein thrombosis and venous thrombosis, and in patients with atrial fibrillation. Although the available safety data are encouraging, most studies were underpowered for efficacy endpoints.