Marina Serper1,2,3, Ethan M Weinberg2, Jordana B Cohen4,5, Peter P Reese3,4,5, Tamar H Taddei6,7, David E Kaplan1,2. 1. Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA. 2. Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 3. Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA. 4. Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA. 5. Renal-Electrolyte and Hypertension Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 6. VA Connecticut Healthcare System, West Haven, CT. 7. Division of Gastroenterology, Yale University School of Medicine, New Haven, CT.
Abstract
BACKGROUND AND AIMS: Outcomes with anticoagulation (AC) are understudied in advanced liver disease. We investigated effects of AC with warfarin and direct oral anticoagulants (DOACs) on all-cause mortality and hepatic decompensation as well as ischemic stroke, major adverse cardiovascular events, splanchnic vein thrombosis, and bleeding in a cohort with cirrhosis and atrial fibrillation (AF). APPROACH AND RESULTS: This was a retrospective, longitudinal study using national data of U.S. veterans with cirrhosis at 128 medical centers, including patients with cirrhosis with incident AF, from January 1, 2012 to December 31, 2017 followed through December 31, 2018. To assess the effects of AC on outcomes, we applied propensity score (PS) matching and marginal structural models (MSMs) to account for confounding by indication and time-dependent confounding. The final cohort included 2,694 veterans with cirrhosis with AF (n = 1,694 and n = 704 in the warfarin and DOAC cohorts after PS matching, respectively) with a median of 4.6 years of follow-up. All-cause mortality was lower with warfarin versus no AC (PS matched: hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.55-0.76; MSM models: HR, 0.54; 95% CI, 0.40-0.73) and DOACs versus no AC (PS matched: HR, 0.68; 95% CI, 0.50-0.93; MSM models: HR, 0.50; 95% CI, 0.31-0.81). In MSM models, warfarin (HR, 0.29; 95% CI, 0.09-0.90) and DOACs (HR, 0.23; 95% CI, 0.07-0.79) were associated with reduced ischemic stroke. In secondary analyses, bleeding was lower with DOACs compared to warfarin (HR, 0.49; 95% CI, 0.26-0.94). CONCLUSIONS: Warfarin and DOACs were associated with reduced all-cause mortality. Warfarin was associated with more bleeding compared to no AC. DOACs had a lower incidence of bleeding compared to warfarin in exploratory analyses. Future studies should prospectively investigate these observed associations.
BACKGROUND AND AIMS: Outcomes with anticoagulation (AC) are understudied in advanced liver disease. We investigated effects of AC with warfarin and direct oral anticoagulants (DOACs) on all-cause mortality and hepatic decompensation as well as ischemic stroke, major adverse cardiovascular events, splanchnic vein thrombosis, and bleeding in a cohort with cirrhosis and atrial fibrillation (AF). APPROACH AND RESULTS: This was a retrospective, longitudinal study using national data of U.S. veterans with cirrhosis at 128 medical centers, including patients with cirrhosis with incident AF, from January 1, 2012 to December 31, 2017 followed through December 31, 2018. To assess the effects of AC on outcomes, we applied propensity score (PS) matching and marginal structural models (MSMs) to account for confounding by indication and time-dependent confounding. The final cohort included 2,694 veterans with cirrhosis with AF (n = 1,694 and n = 704 in the warfarin and DOAC cohorts after PS matching, respectively) with a median of 4.6 years of follow-up. All-cause mortality was lower with warfarin versus no AC (PS matched: hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.55-0.76; MSM models: HR, 0.54; 95% CI, 0.40-0.73) and DOACs versus no AC (PS matched: HR, 0.68; 95% CI, 0.50-0.93; MSM models: HR, 0.50; 95% CI, 0.31-0.81). In MSM models, warfarin (HR, 0.29; 95% CI, 0.09-0.90) and DOACs (HR, 0.23; 95% CI, 0.07-0.79) were associated with reduced ischemic stroke. In secondary analyses, bleeding was lower with DOACs compared to warfarin (HR, 0.49; 95% CI, 0.26-0.94). CONCLUSIONS:Warfarin and DOACs were associated with reduced all-cause mortality. Warfarin was associated with more bleeding compared to no AC. DOACs had a lower incidence of bleeding compared to warfarin in exploratory analyses. Future studies should prospectively investigate these observed associations.
Authors: N M Intagliata; Z H Henry; H Maitland; N L Shah; C K Argo; P G Northup; S H Caldwell Journal: Dig Dis Sci Date: 2016-01-02 Impact factor: 3.199
Authors: K Fujii; M Kishiwada; T Hayashi; J Nishioka; E C Gabazza; T Okamoto; S Uemoto; K Suzuki Journal: J Thromb Haemost Date: 2006-09-22 Impact factor: 5.824
Authors: Adeel A Butt; Kathleen McGinnis; Maria C Rodriguez-Barradas; Stephen Crystal; Michael Simberkoff; Matthew Bidwell Goetz; David Leaf; Amy C Justice Journal: AIDS Date: 2009-06-19 Impact factor: 4.177
Authors: Jordana B Cohen; Debbie L Cohen; Daniel S Herman; John T Leppert; James Brian Byrd; Vivek Bhalla Journal: Ann Intern Med Date: 2020-12-29 Impact factor: 25.391
Authors: Nadim Mahmud; Zachary Fricker; James D Lewis; Tamar H Taddei; David S Goldberg; David E Kaplan Journal: Clin Gastroenterol Hepatol Date: 2021-07-08 Impact factor: 13.576