Liver Disease History Does Not Alter Efficacy and Safety of Edoxaban in AF

Patients with atrial fibrillation (AF) and a history of liver disease who are receiving oral anticoagulation have an increased risk for bleeding but not for thromboembolic events compared with those without liver disease, according to results published in The Journal of the American College of Cardiology.

The study included 21,105 participants with AF who were randomly assigned at a ratio of 1:1:1 to receive a higher-dose edoxaban regimen (60 mg daily, or 30 mg daily in patients with creatinine clearance 30 to 50 mL/min, body weight ≤60 kg, or concomitant use of potent P-glycoprotein inhibitors), a lower-dose edoxaban regimen (30 mg daily, or 15 mg daily if dose reduction was required), or warfarin dose adjusted to an international normalized ratio of 2.0 to 3.0.

The researchers defined history of liver disease as investigator-reported liver disease of >2-fold transaminase elevation at randomization. The study’s primary efficacy and safety end points were stroke or systemic embolic event and major bleeding.

Of all participants, 5.1% (n=1083) had a history of liver disease. These participants had a higher prevalence of many comorbidities.

The results indicated that the adjusted risk for stroke or systemic embolic event was similar among participants with a history of liver disease and those without (adjusted hazard ratio [aHR] 0.90; 95% CI, 0.67-1.22; P =.50). However, participants with liver disease were more likely to experience major bleeding compared with those without liver disease (aHR, 1.38; 95% CI, 1.10-1.74; P =.006).

The researchers did not find any significant differences in the pharmacokinetics or pharmacodynamics of edoxaban in participants with liver disease compared with those without.

Compared with warfarin, the higher-dose edoxaban regimen had an HR of 0.86 (95% CI, 0.73-1.01) for stroke or systemic embolic event for participants without liver disease and an HR of 1.11 (95% CI, 0.54-2.30) for those with liver disease. For major bleeding compared with warfarin, higher-dose edoxaban regimen had an HR of 0.80 (95% CI, 0.70-0.91) in participants without liver disease and 0.91 (95% CI, 0.56-1.47) for those with liver disease.

The researchers did not find any significant differences in hepatic adverse events among the 2 treatment groups.

“In the setting of high risk of bleeding in patients with liver disease, edoxaban should be preferred over warfarin for the prevention of stroke and bleeding in patients with AF and history of liver disease,” the researchers wrote.

Disclosure: Multiple authors disclosed affiliations with pharmaceutical companies. See the reference for complete disclosure information.

Reference

Qamar A, Antman EM, Ruff CT, et al. Edoxaban versus warfarin in patients with atrial fibrillation and history of liver disease. J Am Coll Cardiol. 2019;74(2):179-189.