Key result
DOACs linked to ~21% higher mortality than warfarin for DVT/PE in cirrhosis.
Why the study?
Does direct oral anticoagulant (DOAC) initiation compared with warfarin initiation affect mortality, liver transplantation, and bleeding/ischemic outcomes across indications in patients with cirrhosis?
Cohort (n=93,663)
Yes
Does direct oral anticoagulant (DOAC) initiation compared with warfarin initiation affect mortality, liver transplantation, and bleeding/ischemic outcomes across indications in patients with cirrhosis?
In patients with cirrhosis, DOACs offer favorable bleeding profiles and similar survival compared to warfarin in atrial fibrillation, but are associated with higher mortality and reduced liver transplant access in venous thrombosis partially due to lack of warfarin-induced INR MELD inflation.
Answers are grounded in this paper and cite their sources.
Supports DOAC consideration across indications in cirrhosis; leaves open randomized confirmation of comparative safety and efficacy.
Background and aims Comparative data on oral anticoagulant safety and efficacy across indications in cirrhosis remain limited. We compared outcomes following direct oral anticoagulant (DOAC) versus warfarin initiation in a nationwide US cohort. Methods The primary cohort (Epic Cosmos; 2019-2024) compared propensity score-matched DOAC and warfarin initiators across atrial fibrillation (AF), deep vein thrombosis with or without pulmonary embolism (DVT/PE), and portal vein thrombosis (PVT). Competing-risk regression models evaluated death, liver transplantation (LT), and hemorrhagic and ischemic outcomes. An ancillary cohort (US transplant registry-Medicare linkage; 2021-2022) evaluated INR-driven MELD inflation as a mediator among waitlisted patients. Results Among 93,663 initiators in the primary cohort, DOAC versus warfarin initiation in AF was associated with similar mortality and LT rates but lower overall major bleeding and non-gastrointestinal bleeding, including intracranial hemorrhage. In DVT/PE and PVT, DOAC versus warfarin initiation was associated with higher mortality (DVT/PE: sHR 1.21 [95%CI 1.10-1.34]; PVT: sHR 1.43 [1.24-1.65]) and markedly lower LT rates (DVT/PE: sHR 0.25 [0.17-0.38]; PVT: sHR 0.23 [0.17-0.32]); gastrointestinal bleeding was higher with DOACs than warfarin in PVT (sHR 1.26 [1.06-1.50]). Multiple sensitivity analyses corroborated these findings. In the ancillary cohort (n=284), warfarin-associated INR elevation partially mediated LT access differences (percentage mediated: 29%). Conclusions In cirrhosis, DOAC versus warfarin initiation was associated with similar mortality but favorable bleeding outcomes in AF. However, in venous thrombosis, DOAC initiators had higher mortality and lower LT access than warfarin initiators; warfarin-related INR inflation partly explained LT disparities. These findings support indication-specific treatment and reconsideration of INR handling in the US LT allocation system amid increasing DOAC use.
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Tanaka et al. (2026) conducted a cohort in Cirrhosis requiring oral anticoagulation for atrial fibrillation, deep vein thrombosis with or without pulmonary embolism, or portal vein thrombosis (n=93,663). Direct oral anticoagulant (DOAC) initiation vs. Warfarin initiation was evaluated on Death, liver transplantation, and hemorrhagic and ischemic outcomes across indications (sHR 1.21, 95% CI 1.10-1.34). DOAC vs warfarin initiation in cirrhosis had similar mortality and less major bleeding in AF, but higher mortality in DVT/PE and PVT.
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