Edoxaban is similar to optimized enoxaparin-warfarin with regard to efficacy and safety but is associated with lower rates of stroke, systemic embolism, myocardial infarction, and cardiovascular death in patients with atrial fibrillation (AF) who are at risk for stroke, according to an ancillary analysis of the Edoxaban vs Warfarin in Subjects Undergoing Cardioversion of Atrial Fibrillation (ENSURE-AF, ClinicalTrials.gov identifier: NCT02072434) study.
In the ENSURE-AF study, the primary efficacy end point was a composite of stroke, systemic embolic event, myocardial infarction, and cardiovascular death, and the safety end point was a composite of major and clinically relevant nonmajor bleeding. Researchers randomly assigned 1095 patients to edoxaban and 1104 patients to optimized enoxaparin-warfarin.
The mean HAS-BLED (hypertension, age, stroke, bleeding tendency/predisposition, labile international normalized ratio, elderly age/frailty, drugs) score was 0.9 (standard deviation [SD], 0.8) and the mean CHA2DS2-VASc score was 2.6 (SD, 1.5 [arm 1] and 1.4 [arm 2]).
In patients at risk for thromboembolism with CHA2DS2-VASc scores >2, there was a trend toward lower odds ratios (ORs) primarily for the efficacy end point, but this trend was not considered significant. In addition, higher ORs were found to be nonsignificantly associated with a HAS-BLED score ≥3. Investigators observed significant associations between CHA2DS2-VASc and time to therapeutic range (P =.0004) and HAS-BLED and time in therapeutic range (P =.0286).
The overall event rates were low in both arms (as assessed by the HAS-BLED and CHA2DS2-VASc scores), and the observational associations of the scores to time in therapeutic range and time to therapeutic range were considered exploratory only and do not explain mechanisms underlying these events. The small sample size and short follow-up period are 2 additional limitations associated with the findings.
Patients with higher CHA2DS2-VASc scores in the ENSURE-AF study also achieved therapeutic range sooner, an observation the investigators suggested was because of the possibility that, “higher-risk patients may have had closer attention to their anticoagulation control or better compliance with their treatments.”
Lip GYH, Merino JL, Dan GA, et al. Relation of stroke and bleeding risk profiles to efficacy and safety of edoxaban for cardioversion of atrial fibrillation (from the Edoxaban versus warfarin in subjects undergoing cardioversion of atrial fibrillation [ENSURE-AF] study) [published online October 26, 2017]. Am J Cardiol. doi:10.1016/j.amjcard.2017.10.008