Anticoagulation Control in Warfarin-Treated Patients Undergoing Cardioversion of Atrial Fibrillation (from the Edoxaban Versus Enoxaparin-Warfarin in Patients Undergoing Cardioversion of Atrial Fibrillation Trial)

In the Edoxaban Versus Enoxaparin Warfarin in Patients Undergoing Cardioversion of Atrial Fibrillation (ENSURE-AF) study (NCT 02072434), edoxaban was compared with enoxaparin warfarin in 2,199 patients undergoing electrical cardioversion of nonvalvular atrial fibrillation (AF). In this multicenter prospective randomized open blinded end-point trial, we analyzed patients randomized to enoxaparin warfarin. We determined time to achieve therapeutic range (TtTR); time in therapeutic range (TiTR); their clinical determinants; relation to sex, age, medical history, treatment, tobacco use, race risk (SAMe-TT2R2) score; and impact on primary end points (composite of stroke, systemic embolic event[SEE], myocardial infarction [Mill, and cardiovascular death [CVD] and composite of major + clinically relevant nonmajor bleeding). Among 1,104 patients randomized to enoxaparin warfarin, 27% were naive to oral anticoagulants. Mean age was 64.2 +/- 11 years and mean congestive heart failure, hypertension, age (doubled), diabetes mellitus, prior stroke or transient ischemic attack (doubled), vascular disease, age 6574, female (CHA(2)DS(2)-VASc) score was 2.6. Mean TtTR was 7.7 days (median 7 days) and mean TiTR after reaching an international normalized ratio of 2.0 to 3.0 was 71 %. In 695 patients who had an INR <2.0 before the first dose and who reached an INR >= 2.0, 436 had a SAMe-TT2R2 score <= 2 and 259 had a score >2. On multivariate regression, an independent predictor of extended TtTR was creatinine clearance (p = 0.02). TtTR was marginally related to stroke/SEE/MI/CVD (p = 0.06; odds ratio 0.23, 95% confidence interval 0.02 to 1.17) but not to any bleeding. Independent predictors of TiTR were previous vitamin K antagonist experience (p<0.01) and low hypertension, abnormal renal or liver function, stroke, bleeding, labile INRs, age >65, concomitant drugs or alcohol (HAS-BLED) score (p = 0.02). TiTR was related to any bleeding (p = 0.02; odds ratio 0.39, 95 % confidence interval 0.16 to 0.88), but not stroke/SEE/MI/CVD. In this cohort of warfarin users with a high TiTR no difference was seen between TtTR and TiTR in relation to SAMe-TT2R2 score. In conclusion, even in this short-term study, TiTR was significantly related to bleeding events. (C) 2017 Elsevier Inc. All rights reserved.