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In AF, liver disease confers elevated bleeding risk after anticoagulation
Major bleeding risk was elevated in patients with atrial fibrillation and a history of liver disease after the use of oral anticoagulants, according to findings published in the Journal of the American College of Cardiology.
Researchers also found that a history of liver disease did not alter the efficacy of edoxaban (Savaysa, Daiichi Sankyo) compared with warfarin.
Arman Qamar, MD, MPH, clinical fellow in the TIMI Study Group at Brigham and Women’s Hospital and Harvard Medical School, and colleagues investigated the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of edoxaban compared with warfarin in patients with AF and a history of liver disease.
AF and liver disease
“There are very little data available on patients with liver disease treated with newer oral anticoagulants (NOACs), and even the data in patients treated with vitamin K antagonists, like warfarin, are sparse and of low to moderate quality,” Robert P. Giugliano, MD, SM, FACC, FAHA, a physician of cardiovascular medicine at Brigham and Women’s Hospital, associate professor of medicine at Harvard Medical School and the senior investigator of the TIMI Study Group, told Cardiology Today. “In this large randomized controlled trial comparing a NOAC, edoxaban, with warfarin, we realized we had an opportunity to compare outcomes between these treatments in patients with and without liver disease. In addition, we had detailed pharmacokinetic and pharmacologic data available on patients that could help us interpret the results.”
The researchers examined data from the randomized, double-blind ENGAGE AF-TIMI 48 trial that compared edoxaban with warfarin in patients with AF who were followed for 2.8 years.
Primary efficacy and safety endpoints of stroke or systematic embolic event (SSEE) and major bleeding were evaluated stratified by a history of liver disease, Qamar and colleagues wrote.
The researchers found in 21,105 patients, 5.1% had a history of liver disease. The patients also had a higher prevalence of many comorbidities.
In the overall cohort, adjusted risk for SSEE was similar in those with and without liver disease (adjusted HR = 0.9; 95% CI, 0.67-1.22), Qamar and colleagues wrote. Patients with liver disease more often had major bleeding than those without it (aHR = 1.38; 95% CI, 1.1-1.74).
The HRs for SSEE for edoxaban compared with warfarin did not significantly differ in patients with and without liver disease (liver disease, aHR = 1.11; 95% CI, 0.54-2.3; no liver disease, aHR = 0.86; 95% CI, 0.73-1.01; P for interaction = .47), the researchers wrote.
The HRs for major bleeding for edoxaban vs. warfarin also did not significantly differ between those with and without liver disease (liver disease, aHR = 0.91; 95% CI, 0.56-1.47; no liver disease, aHR = 0.8; 95% CI, 0.7-0.91; P for interaction = .63).
“For the first time with a NOAC, there are now clinical outcome data, supported by pharmacokinetic and pharmacodynamic results, to support the use of a NOAC — in this case, edoxaban — in a randomized comparison with warfarin from a randomized trial that analyzed patients with liver disease,” Giugliano told Cardiology Today.
Evidence for edoxaban
In a related editorial, Eue-Keun Choi, MD, PhD, and So-Ryoung Lee, MD, of the division of cardiology in the department of internal medicine at Seoul National University in South Korea, wrote: “Stroke prevention in AF patients with liver disease is important, and the current study provides evidence for the use of edoxaban in this population, with better or at least comparable clinical efficacy and safety compared with warfarin. However, the study results were based on patients with ‘mild’ liver disease; therefore, further studies are need to expand the safety zone of [direct oral anticoagulants] to patients with more than ‘mild’ liver disease.” – by Earl Holland Jr.
Disclosures: Qamar reports he received fees for educational activities from the American College of Cardiology, the Clinical Exercise Physiology Association, Medscape, Pfizer and the Society for Cardiovascular Angiography and Interventions. Giugliano reports he received consultant fees and honoraria from Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Janssen, Lexicon, Merck, Pfizer and Portola and research grants from Daiichi Sankyo and Merck. Please see the study for all other authors’ relevant financial disclosures. Choi reports he received research grant support from Bristol-Myers Squibb/Pfizer and Daiichi Sankyo. Lee reports no relevant financial disclosures.