Results from the global phase 3b ENSURE-AF ( EdoxabaN vs warfarin in subjectS UndeRgoing cardiovErsion of AtrialFibrillation ) study of 2,199 patients with non-valvular atrial fibrillation ( NVAF ) undergoing electrical cardioversion ( low-energy shocks to trigger normal heart rhythm ). The study has shown that oral, once-daily Edoxaban ( Lixiana ) met the study’s primary endpoints, demonstrating comparable efficacy and safety to well-managed Enoxaparin / Warfarin ( mean time in therapeutic range on Warfarin was 70.8% ) for the prevention of stroke and other blood clot complications, were presented at the ESC Congress 2016 in Rome, and published in The Lancet.
Edoxaban is an oral, once-daily, direct factor Xa inhibitor.
ENSURE-AF was designed to evaluate the efficacy and safety of once-daily Edoxaban versus Enoxaparin / well-managed Warfarin in patients with NVAF undergoing electrical cardioversion.
For the primary efficacy outcome evaluating the composite of stroke, systemic embolic event, myocardial infarction, and cardiovascular mortality, Edoxaban demonstrated a similar incidence compared to Enoxaparin / Warfarin ( 0.5% vs 1.0%, respectively ) ( odds ratio, OR=0.46; 95% confidence interval [ CI ], 0.12 to 1.43 ). The main difference between the treatment groups was driven by cardiovascular mortality, with one event in the Edoxaban group and five events in the Enoxaparin / Warfarin group ( 0.1% vs. 0.5%, respectively ).
For the combined principal safety outcome of the incidence of major and clinically-relevant non-major ( CRNM ) bleeding, events occurred in 1.5% of patients in the Edoxaban group and 1.0% in the Enoxaparin / Warfarin group ( OR=1.48; 95% CI, 0.64 to 3.55 ). The difference was statistically non-significant.
The incidence of major bleeding was numerically lower in the Edoxaban group compared to the Warfarin group ( 0.3% vs. 0.5%, respectively ) ( OR=0.61; 95% CI, 0.09 to 3.13 ).
No intracranial bleedings were reported in the study in either of the treatment groups. No fatal bleeding was reported in the Edoxaban group versus one patient in the Enoxaparin / Warfarin group.
The result for the net clinical outcome ( composite of stroke, systemic embolic event, myocardial infarction, cardiovascular mortality, and major bleeding ) was 0.7% in the Edoxaban group and 1.4% in the Enoxaparin / Warfarin group ( OR=0.50; 95% CI, 0.19–1.25 ) during the overall study period. Of note, the trial was not adequately powered to demonstrate statistical differences for efficacy or safety endpoints, but provides further insights on the use of Edoxaban in the setting of electrical cardioversion of non-valvular atrial fibrillation.
In the ENSURE-AF study, patients were stratified according to cardioversion approach ( TEE or non-TEE ), a patient’s prior experience taking anticoagulants at the time of randomization ( i.e. anticoagulant-experienced or naïve ), and Edoxaban dose ( 60 mg once-daily or reduced 30 mg once-daily ). Patients were randomized in a 1:1 ratio to two treatment groups within each stratum. Edoxaban was dosed at 60 mg once-daily. The dose was reduced to Edoxaban 30 mg once-daily for those patients if one or more factors ( renal impairment, low body weight, or concomitant use of certain P-glycoprotein inhibitors ) were present. Patients in the Enoxaparin / Warfarin group received optimized standard of care such that those with International Normalized Ratio ( INR ). ( Xagena )
Source: Daiichi Sankyo, 2016