Direct-Acting Oral Anticoagulants (DOACs) in Cirrhosis and Cirrhosis-Associated Portal Vein Thrombosis

Abstract

Direct-acting oral anticoagulants (DOACs) have provided benefit in patients requiring anticoagulation for certain diseases by decreasing the burden of subcutaneous injections and the requirement for frequent monitoring through regular blood tests, to ensure adequacy of the therapeutic doses. Studies have demonstrated DOACs to be as safe, and in some instance safer, compared with traditional anticoagulants in the general population. However, the studies evaluating DOACs excluded patients with cirrhosis, a condition associated with an increased risk of developing portal vein thrombosis (PVT). Warfarin or low-molecular weight heparin are the standard-of-care treatment for acute PVT in cirrhosis, although there is enthusiasm in a paradigm shift switching to DOACs for the treatment of acute PVT in cirrhosis, particularly since the release of DOAC antidotes. This article reviews the current Food and Drug Administration-approved DOACs, hepatic metabolism of DOACs, pharmacokinetics of DOACs in patients with cirrhosis, safety of DOACs (including bleeding, hepatotoxicity, and pregnancy), current treatment guidelines for PVT in cirrhosis, and studies evaluating the use of DOACs in cirrhosis and for the treatment of PVT in cirrhosis. The potential use of DOACs for PVT primary prophylaxis in at-risk patients with cirrhosis and the possible antifibrotic effects of DOACs are also discussed.

Anticoagulation Favors Thrombus Recanalization and Survival in Patients With Liver Cirrhosis and Portal Vein Thrombosis: Results of a Meta-Analysis

“…However, a higher rate of recanalization obtained by DOACs has been reported in only a single study [20]. In addition, the safety of DOACs is unclear in patients with advanced or decompensated cirrhosis [54]. Therefore, such a conclusion needs to be validated by a head-to-head randomized comparison.…”

Outcomes of long‐term anticoagulant treatment for the secondary prophylaxis of splanchnic venous thrombosis

“…In the literature, the results deriving from DOACs use in SVT are based on limited and case studies in the acute SVT. These studies have shown acceptable safety and efficacy profile also in cirrhotic patients 14‐18 . A randomized trial of rivaroxaban versus warfarin was performed for the acute non‐neoplastic portal vein thrombosis showing a remarkable efficacy and safety of the DOACs in the acute hepatitis C virus‐related PVT 19 .…”

Mortality and Hepatic Decompensation in Patients With Cirrhosis and Atrial Fibrillation Treated With Anticoagulation

“…( 1 ) Direct‐acting oral anticoagulants (DOACs), a newer class of anticoagulants that either directly inhibit the activation of factor Xa (apixaban, betrixaban, endoxaban, and rivaroxaban) or thrombin (dabigatran), have become the most commonly prescribed oral agents to prevent ischemic stroke in AF. ( 6 ) However, registration trials for these agents specifically excluded patients with advanced liver disease because of safety concerns given that all DOACs undergo hepatic metabolism. ( 8 ) Emerging retrospective studies and meta‐analyses generally support the efficacy and safety of both warfarin and DOAC utilization in patients with cirrhosis with AF, ( 9‐12 ) and newer data suggest that DOACs are equally as effective as warfarin at preventing ischemic stroke.…”