The relationship of renal function to outcome: A post hoc analysis from the EdoxabaN versus warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation (ENSURE-AF) study

• Published in: The American heart journal Vol. 193; pp. 16 - 22
• Main Authors: Lip, Gregory Y.H., Al-Saady, Naab, Ezekowitz, Michael D., Banach, Maciej, Goette, Andreas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2017; Elsevier Limited
• Subjects: Aged; Anticoagulants; Anticoagulants - administration & dosage; Atrial Fibrillation - complications; Atrial Fibrillation - therapy; Bleeding; Cardiac arrhythmia; Cardiovascular disease; Clinical outcomes; Continuity (mathematics); Creatinine; Creatinine - metabolism; Dose-Response Relationship, Drug; Drug dosages; Effectiveness; Electric Countershock - methods; Factor Xa Inhibitors - administration & dosage; Female; Fibrillation; Glomerular Filtration Rate - drug effects; Glycoproteins; Heart; Humans; Kidney - drug effects; Kidney - physiopathology; Kidney diseases; Male; Middle Aged; P-Glycoprotein; Patients; Pyridines - administration & dosage; Renal function; Safety; Strata; Stroke; Thiazoles - administration & dosage; Thromboembolism; Thromboembolism - etiology; Thromboembolism - prevention & control; Treatment Outcome; Warfarin; Warfarin - administration & dosage; Weight reduction
• ISSN: 0002-8703; 1097-6744; 1097-6744
• DOI: 10.1016/j.ahj.2017.07.010

The ENSURE-AF study (NCT 02072434) of anticoagulation for electrical cardioversion in nonvalvular atrial fibrillation (NVAF) showed comparable low rates of bleeding and thromboembolism between the edoxaban and the enoxaparin-warfarin treatment arms. This post hoc analysis investigated the relationship between renal function and clinical outcomes. ENSURE-AF was a multicenter, PROBE evaluation trial of edoxaban 60 mg, or dose reduced to 30 mg/d for weight≤60 kg, creatinine clearance (CrCl; Cockcroft-Gault) ≤50 mL/min, or concomitant P-glycoprotein inhibitors compared with therapeutically monitored enoxaparin-warfarin in 2,199 NVAF patients undergoing electrical cardioversion. Efficacy and safety outcomes and time in therapeutic range in the warfarin arm were analyzed in relation to CrCl in prespecified ranges ≥15 and ≤30, >30 and ≤50, >50 and <80, and ≥80 mL/min, and an exploratory ≥95-mL/min analysis. A total of 1,095 subjects were randomized to edoxaban and 1,104 to enoxaparin-warfarin. Mean age was 64.3±10 and 64.2±11 years. Mean time in therapeutic range was progressively lower with reducing CrCl strata, being 66.8% in those with CrCl >30 to ≤50 compared with 71.8% in those with CrCl ≥80. The odds ratios for the primary efficacy and safety end points were comparable for the different predefined renal function strata; given the small numbers, the 95% CI included 1.0. In the subset of those with CrCl ≥95, the odds ratios showed consistency with the other CrCl strata. When CrCl was assessed as a continuous variable, there was a nonsignificant trend toward higher major or clinically relevant nonmajor bleeding with reducing CrCl levels, with no significant differences between the 2 treatment arms. When we assessed CrCl at baseline compared with end of treatment, there were no significant differences in CrCl change between the edoxaban and enoxaparin-warfarin arms. The proportions with worsening of renal function (defined as a decrease of >20% from baseline) were similar in the 2 treatment arms. Given the small number of events in ENSURE-AF, no effect of renal (dys)function was demonstrated in comparing edoxaban to enoxaparin-warfarin for cardioversion; efficacy and safety of edoxaban remained consistent even in patients with normal or supranormal renal function.