Edoxaban and warfarin are equally effective in reducing the risk of stroke, systemic embolic events and major bleeding in patients with atrial fibrillation and a history of liver disease, researchers reported in the Journal of the American College of Cardiology this month.
Lead author Arman Qamar, MD, MPH, and colleagues at Brigham and Women’s Hospital and Harvard Medical School in Boston said that while patients with liver disease are at a known elevated risk for thrombosis and bleeding events—their most common cause of death is from CVD—they’re typically excluded from studies of direct oral anticoagulants (DOACs). Liver disease patients are also predisposed to AFib, but because of a decreased production of coagulation factors, thrombocytopenia and increased fibrinolysis, they can struggle with standard-of-care anticoagulation agents like warfarin.
DOACs, on the other hand, have been successful in preventing stroke and thromboembolism in the general AFib population, but few studies have included liver disease patients in analyses of drugs like edoxaban.
Qamar et al. evaluated the pharmacokinetics (PK), pharmacodynamics (PD), and clinical efficacy and safety of edoxaban versus warfarin in patients enrolled in the ENGAGE AF-TIMI 48 trial, a randomized, double-blind study that compared edoxaban with warfarin in patients with AFib. Of 21,105 patients studied in ENGAGE AF-TIMI 48, 1,083—5.1%—also had a history of liver disease.
The authors said patients with historical liver disease, defined as investigator-reported disease or greater than twofold transaminase elevation at patient randomization, also had a higher prevalence of “many” comorbidities compared to the general AFib population. The adjusted risks of stroke or systemic embolic events (SSEE) were similar between the two groups, but major bleeding was 38% more common in patients with liver disease.
Qamar and co-authors didn’t report any significant differences in PK or PD assessment of edoxaban in patients with versus without liver disease. The hazard ratios for higher-dose edoxaban versus warfarin for SSEE were 0.86 in patients without and 1.11 in patients with liver disease, and for major bleeding those corresponding HRs were 0.80 in patients without and 0.91 in patients with liver disease.
“Among patients with AF receiving oral anticoagulation, bleeding, but not thromboembolic events, was increased in patients with liver disease,” the researchers wrote in JACC. “A history of liver disease did not alter the relative efficacy and safety of edoxaban compared with warfarin.”
The authors did warn that, though their results found few differences between the two drugs, off-label use of low-dose DOACs to prevent thrombotic events should, “in general, be discouraged.” Still, when faced with a choice between edoxaban and warfarin, the former is preferred to prevent stroke and bleeding in patients with AFib and a history of liver disease.
“This analysis represents the first report of PK, PD, clinical efficacy and safety of edoxaban in patients with history of liver disease in a randomized trial of patients with AFib,” Qamar and co-authors wrote. “Patients with advanced liver disease are at high risk of thrombotic and bleeding events, and large prospective trials are needed to evaluate the efficacy and safety of target-specific oral anticoagulant agents in this vulnerable population.”