The factor Xa inhibitor edoxaban might reduce the risk of several adverse events—including stroke, major bleeding and all-cause death—when compared to warfarin, according to a real-world study of Korean patients with atrial fibrillation (AFib).
According to the authors, direct oral anticoagulants (DOACs) have proven to be equally effective as warfarin for stroke prevention in patients with AFib—and arguably safer based on trials and real-world data. But few Asian patients were enrolled in those studies, necessitating further research of the specific population.
Lead author So-Ryoung Lee, MD, and colleagues analyzed a propensity-score matched cohort of patients with AFib who were new users of edoxaban or warfarin. Some 4,061 patients were on edoxaban, while 12,183 were taking warfarin. Given that the trial was focused on primary prevention, the researchers excluded individuals with histories of ischemic stroke, intracerebral hemorrhage or gastrointestinal bleeding.
The median CHA2DS2-VASc stroke risk score was 3 for the entire cohort, and the average age was 70.
Published in the Journal of the American College of Cardiology, the results indicated:
- Edoxaban users had a 31 percent reduced risk of ischemic stroke when compared to warfarin users.
- Compared to warfarin, the DOAC was also associated with risk reductions of 60 percent for intracerebral hemorrhage, 40 percent for gastrointestinal bleeding-related hospitalizations, 47 percent for major bleeding hospitalizations and 28 percent for all-cause death.
- All subgroup analyses based on age, sex, CHA2DS2-VASc score, renal function and edoxaban dose showed improved clinical outcomes with the once-daily factor Xa inhibitor.
The authors noted their paper was the first to compare the safety and effectiveness of edoxaban and warfarin with a specific focus on Asian patients. They offered a few potential explanations for their findings.
“Asian patients with AFib have a smaller body size than Western patients with AFib; thus, the plasma concentrations of edoxaban might not decrease in those with high CrCl (creatinine clearance) levels”—an association which was highlighted in previous studies with predominantly non-Asian patients, the researchers pointed out.
Also, there has been evidence of a lower time in therapeutic range (TTR) for Asian patients on warfarin than individuals from other races, which may have heightened the comparative benefit of edoxaban. Although both a 30 and 60 mg dose of the factor Xa inhibitor was associated with better clinical outcomes than warfarin, Lee et al. said the available evidence supports the use of the higher concentration in most cases.
“Our results demonstrated the effectiveness and safety of edoxaban 60 mg, and this was consistent with a previous meta-analysis that reported that regular doses of DOACs were effective and safe enough in Asian patients, perhaps even more than among the non-Asian population. … Edoxaban 30 mg use is only recommended in patients who have at least one dose reduction criteria according to the drug label, that is, renal impairment (CrCl 30 to 50 ml/min), body weight of ≤60 kg, or concomitant use of a potent phosphorylated glycoprotein inhibitor,” they wrote.
The researchers acknowledged the following limitations of their work: They weren’t able to evaluate TTR for the warfarin group; there was a shorter follow-up duration for edoxaban patients given its more recent introduction into the marketplace; and some of the subanalyses contained insufficient numbers of edoxaban users to draw definitive conclusions.
The authors of an accompanying editorial added to that list, pointing out the lower event rates in the edoxaban group “may just indicate the presence of strong drug selection bias.” Shinya Goto, MD, PhD, and Shinichi Goto, MD, PhD—both with Tokai University School of Medicine in Japan—said the difference in follow-up periods is a particularly important limitation.
Median follow-up was 0.3 years in the edoxaban cohort and 0.9 years for warfarin patients. Incidence rates of events were calculated per every 100 person-years at risk, but that may not fully adjust for the varying follow-up durations, the Gotos wrote.
“The slight statistical difference between edoxaban and warfarin (for ischemic stroke) may be refuted by a longer term of follow-up, even with the same dataset,” they noted, adding the data provided by Lee et al. should only be viewed as hypothesis-generating.
Daniel joined TriMed’s Chicago editorial team in 2017 as a Cardiovascular Business writer. He previously worked as a writer for daily newspapers in North Dakota and Indiana.