ESC Congress FA eBook 2016 - 11D

treatment options for AF. Goal-based care, supported by
a table for guidance, was recommended.
NOACs in the Setting of Cardioversion
A substantial risk of stroke remains despite cardioversion, thus requiring adequate anticoagulant therapy in
patients with AF. However, the data have been limited.
For warfarin, there are only observational data, with
no large randomized trial to support its use. Evidence
supporting the use of NOACs is available from post hoc
analyses of the 4 major NOAC vs warfarin trials, one randomized trial comparing rivaroxaban vs warfarin, and a
meta-analysis of these 5 studies.12 At the ESC Congress
new data were presented from the largest trial of OAC in
patients undergoing cardioversion (ENSURE-AF).
The ENSURE-AF trial was conducted to compare
edoxaban with standard therapy, and also to evaluate
the optimal approach for the use of NOACs and TEE in
patients with AF undergoing cardioversion.5 The prospective, randomized, open-label, blinded evaluation,
international trial randomized 2199 patients with documented AF ≥ 48 hours and ≤ 12 months, whether or not
they had prior exposure to an anticoagulant or antiplatelet, to edoxaban (60 mg once daily, dose-reduced to 30 mg
for prespecified criteria) or enoxaparin/warfarin.
Mean patient age was 64 years, most were men (66%),
and the mean CHA2DS2-VASc score was 2.6 in the total
population, 2.7 in the TEE stratum, and 2.5 in the nonTEE stratum.
For both treatment arms, the time to cardioversion was
2 days in the TEE-guided stratum and 22 days for the non-
TEE-guided stratum. Of note, enoxaparin was used during the run-in, but was stopped when the INR was > 2.0,
yielding a 70.8% TTR. Edoxaban was given at least 2
hours prior to cardioversion. The primary efficacy endpoint was a composite of stroke, systemic embolic event,
MI, and CV mortality, analyzed by intention to treat. The
primary safety endpoint was major and CRNM bleeding
in patients who received at least one dose of study drug.
Edoxaban was associated with a nonsignificant reduction in the primary efficacy composite outcome of stroke,
SEE, MI, and CV mortality at 56 days post cardioversion
compared with enoxaparin/warfarin (0.5% vs 1.0%, respectively; OR, 0.46; 95% CI, 0.12 to 1.43) in the total
population. Similar findings were present within both
TEE strata.
The primary safety outcome of major and CRNM
bleeding at 31 days post cardioversion showed there
were 16 events in the edoxaban arm and 11 events in the
enoxaparin/warfarin arm, for an event rate of 1.5% vs
1.0% (OR, 1.48; 95% CI, 0.64 to 3.55). Major bleeding
wasinfrequent at 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).

The net clinical benefit, a composite of stroke, SEE,
CV mortality, and major bleeding, also showed a trend
towards a better outcome with edoxaban (8 events vs
16 events with enoxaparin/warfarin; 0.7% vs 1.4% event
rate; OR, 0.50; 95% CI, 0.19 to 1.25).
Edoxaban appears to be an effective and safe alternative to enoxaparin/warfarin for patients with AF undergoing electrical cardioversion and may allow for prompt
cardioversion following the start of anticoagulation,
stated Andreas Goette, MD, St. Vincent's Hospital, Paderborn, Germany, and principal investigator of ENSUREAF.
* In the US, edoxaban (Savaysa®) is not recommended in patients with
AF with creatinine clearance > 95 ml/min due to a trend in reduced
efficacy in the prevention of ischemic stroke compared with warfarin.

References
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