ESC Congress FA eBook 2016 - 10

CLINICAL TRIAL HIGHLIGHTS

ENSURE-AF: Edoxaban Safe,
Similar Efficacy as Warfarin
for AF Cardioversion
Written by Mary Mosley

Official Peer-Reviewed
Highlights From

October 2016

The largest prospective randomized controlled trial of anticoagulation in patients with atrial fibrillation (AF) undergoing electrical cardioversion showed that the direct oral anticoagulant edoxaban
was safe and had a similar effect on the primary outcome as the standard approach of enoxaparin
combined with a vitamin K antagonist (VKA), according to results presented by Andreas Goette,
MD, St. Vincenz Hospital Paderborn and University Hospital Magdeburg, Germany. The results of
the ENSURE-AF study were simultaneously published [Goette A et al. Lancet. 2016].
Data from post hoc analyses of the four non-VKA oral anticoagulants (NOACs) [Renda G et al.
Am J Med 2016] and the randomized X-VERT trial [Cappato R et al. Eur Heart J. 2014] have suggested NOACs could be a safe alternative to the currently recommended VKAs, which are associated with inter- and intrapatient variability and require monitoring of the INR target range.
The open-label, phase 3b, international study randomized 2199 patients with AF for ≥ 48 hours
but ≤ 12 months scheduled for electrical cardioversion and anticoagulation therapy to oncedaily edoxaban (given at least 2 hours before cardioversion) or enoxaparin/warfarin (INR 2.03.0). Three stratifications were also undertaken: 1) transthoracic echocardiography (TEE)-guided
or non-TEE-guided cardioversion; 2) prior use of anticoagulants; and 3) edoxaban dose (60 mg
QD or 30 mg QD). The lower dose of edoxaban is for patients with reduced renal function (creatinine clearance ≥ 15 mL/min and ≤ 50 mL/min), with low body weight (≤ 60 kg), or taking a potent
P-glycoprotein inhibitor.
The mean age was 64 years, most were men (66%), and the mean CHA2DS2-VASc score was
2.6. For both treatment arms, the time to cardioversion was 2 days in the TEE-guided stratum and
23 days for the non-TEEguided stratum. Of note, enoxaparin was used during the run-in, but was
stopped when the INR was > 2.0, yielding a 70.8% time in therapeutic range on warfarin.
For the primary efficacy composite outcome of stroke, systemic embolic event, myocardial
infarction, and cardiovascular mortality at 56 days post cardioversion, a trend was seen toward
a reduction (0.5% with edoxaban vs 1.0% with enoxaparin/VKA; OR, 0.46, 95% CI, 0.12 to 1.43) in
ischemic events in the total population, and also in both TEE strata.
The primary safety outcome of major and clinically relevant nonmajor bleeding at 31 days post
cardioversion showed there were 16 events in the edoxaban arm and 11 events in the enoxaparin/VKA arm, for an event rate of 1.5% vs 1.0% (OR, 1.48; 95% CI, 0.64 to 3.55). Major bleeding
was infrequent, with 3 events and 5 events (0.3% vs 0.5%) in the edoxaban and comparator arms,
respectively (OR, 0.61; 95% CI, 0.09 to 3.13). Rates of any bleeding event were similar (3.0% vs 3.2%;
OR, 0.93; 95% CI, 0.55 to 1.55).
The secondary outcome of net clinical benefit, a composite of stroke, systemic embolic event,
cardiovascular mortality, and major bleeding, also showed a trend towards a better outcome with
edoxaban (8 events vs 16 events with enoxaparin/VKA; 0.7% vs 1.4% event rate; OR, 0.50; 95% CI,
0.19 to 1.25). Renal function did not affect outcomes.
Edoxaban appears to be an effective and safe alternative to enoxaparin/VKA for patients with
AF undergoing electrical cardioversion and may allow for prompt cardioversion following the start
of oral anticoagulation.

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Table of Contents for the Digital Edition of ESC Congress FA eBook 2016