OC 60.3 - Safety and Efficacy of Direct Oral Anticoagulants in Patients with Liver Cirrhosis: A Systematic Review and Meta-Analysis

Tuesday, June 25, 2024

15:15 – 15:30 ICT

Room: Plenary Hall

Presenting Author(s)

Daniel Tham, BHSc

Trainee, Medical Student
Faculty of Medicine, University of Ottawa
Ottawa, Ontario, Canada

Co-Author(s)

WY

Wenhui Yu

Trainee
Faculty of Medicine, University of Ottawa
Ottawa, Ontario, Canada
Lucy Zhao

Trainee
Faculty of Health Sciences, McMaster University
Hamilton, Ontario, Canada
Roger Kou

Trainee
Faculty of Medicine, University of Ottawa
Ottawa, Ontario, Canada
JK

Jayhan Kherani

Trainee
Faculty of Health Sciences, McMaster University
Hamilton, Ontario, Canada
Pei Ye Li

Trainee
Temerty Faculty of Medicine, University of Toronto
Toronto, Ontario, Canada
SS

Shreyas Sreeraman

Resident Trainee
Schulich School of Medicine and Dentistry, University of Western Ontario
London, Ontario, Canada
Ali Eshaghpour

Resident Trainee
Department of Medicine, McMaster University
Hamilton, Ontario, Canada
Allen Li, MD

Resident Physician
University of Toronto, Department of Surgery
Toronto, Ontario, Canada
MC

Mark Crowther

Professor
Department of Medicine, McMaster University
Hamilton, Ontario, Canada

Background: Direct oral anticoagulants (DOACs) are widely used for venous thromboembolism treatment and stroke prophylaxis in atrial fibrillation. Liver cirrhosis increases the risk of conditions necessitating anticoagulation and bleeding, complicating anticoagulation use. DOACs may be suitable in cirrhosis as they have alternative elimination pathways compared with low molecular weight heparins (LMWH) or vitamin K antagonists (VKAs). However, DOAC safety data in cirrhosis is limited as patients with severe Child-Pugh (CP) classes of disease are underrepresented in major trials.

Aims: To synthesize primary evidence on the safety profile of DOACs in patients with severe liver cirrhosis.

Methods: A MEDLINE and Embase literature search from inception to January 2023 identified randomized and non-randomized cohort studies comparing DOACs to LMWH/VKAs in cirrhosis patients. Two reviewers screened and extracted data at title/abstract and full-text levels. Baseline characteristics, CP class, and anticoagulation regimens were extracted. The primary outcome was ISTH major bleeding stratified by CP B&C and CP Unspecified (primary data not stratified by CP class) subgroups. Data were meta-analyzed using a random-effects model and presented as odds ratios with corresponding 95% confidence intervals.

Results: Of 794 articles screened, 2 randomized and 15 non-randomized studies were included (n=5046). There was a statistically significant reduction in major bleeding favouring DOACs overall (OR=0.63 [0.45, 0.89]) and in the CP B&C Exclusive subgroup (OR=0.42 [0.29, 0.62]). The CP Unspecified subgroup demonstrated a non-significant trend towards reduced major bleeding (OR=0.71 [0.48, 1.08]).

Conclusion(s): In this analysis comparing DOACs to LMWH/VKAs in cirrhotic patients, DOACs were associated with a statistically significant reduction in major bleeding overall and in the CP B&C Exclusive subgroup. Future analysis will include secondary outcomes and stratify by DOAC agent, duration, and dosage. Further, prospective studies are required in this patient population as the strength of conclusions are limited by the small number of studies directly comparing DOACs with other anticoagulants.