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Apixaban Lowers Stroke Risk in Patients Undergoing
Cardioversion for Atrial Fibrillation – EMANATE Trial
Apixaban has been shown to lower the risk of stroke vs warfarin in anticoagulation-naïve patients with atrial
fibrillation scheduled for elective cardioversion. Rates of bleeding were similar between the two groups. This
conclusion, based on results of the multicenter, prospective, randomized, open-label Eliquis evaluated in acute
cardioversion coMpared to usuAl treatmeNts for AnTicoagulation in subjects with NVAF (EMANATE) trial, was
presented at the 2017 European Society of Cardiology (ESC) Congress, from August 26–30.
Dr. Michael D. Ezekowitz
M
ichael D. Ezekowitz, MD, PhD, of the Sidney
Kimmel Medical College at Thomas Jefferson
University, Philadelphia, Pennsylvania,
explained that atrial fibrillation is the most com-
mon heart rhythm disorder and is associated with
increased risks of death and stroke. Cardioversion
– restoring andmaintaining the heart’s normal rhythm
– is an integral part of management, as are antico-
agulants, to prevent strokes.
Apixaban blocks the action of the clotting factor Xa
and like other blood thinners, lowers the chance of
blood clots forming. Other blood thinners include
heparin and warfarin. While blood thinners pre-
vent clotting and decrease the chance of having
a stroke, they also increase the risk of bleeding.
Patients scheduled for cardioversion for atrial
fibrillation have traditionally received heparin and/
or warfarin to reduce their risk of stroke. Post hoc
analyses of cardioversion in the RE-LY, ARISTOTLE,
ROCKET-AF, and ENGAGE-AF trials found low event
rates. These trials were limited, however, by pro-
longed periods of precardioversion anticoagulation.
To evaluate more immediate cardioversion, pro-
spective trials comparing rivaroxaban (x-VeRT) and
edoxaban (ENSURE-AF) vs heparin/vitamin K antag-
onism in patients undergoing cardioversion found
comparable efficacy and safety
with low event rates.
Apixaban has not been tested
prospectively in patients under-
going cardioversion.
The purpose of EMANATE was
to compare rates of stroke
and bleeding with apixaban vs
warfarin with heparin in anti-
coagulation-naïve (<48 h of
anticoagulation therapy) patients
scheduled for elective cardiover-
sion of predominantly new-onset
non-valvular atrial fibrillation.
The study included 1500 patients
with atrial fibrillation who were
randomized to apixaban or par-
enteral heparin with warfarin.
Apixaban was administered orally
at a dose of 5 mg twice a day (or
2.5 mg twice a day when two of
the following conditions were met: age ≥80 years,
weight ≤60 kg, or serum creatinine ≥1.5 mg/dL).
At the discretion of the local investigator, patients
could also receive an initial 10 mg or 5 mg loading
dose of apixaban (for study doses of 5 mg and
2.5mg, respectively) if cardioversion was immediate.
Rates of stroke, systemic embolism, death, major
bleeding, and clinically relevant nonmajor bleeding
were compared between the two groups.
Patients treated with apixaban suffered fewer
strokes and similar bleeding to those receiving
usual care. No strokes occurred in the 753 patients
treated with apixaban vs six strokes in the 747
patients who received usual care (P = .01). No
systemic embolic events occurred in either group.
Major bleeds occurred in three and six patients in
the apixaban and usual care groups, respectively.
Clinically significant nonmajor bleeding occurred
in 11 and 13 patients, respectively. Two deaths
occurred in the apixaban group and one in the
heparin/warfarin group.
Of 753 patients in the apixaban group, 342 received
a loading dose. No strokes or systemic embolic
events, one death, one major bleed, and four clin-
ically relevant nonmajor bleeds occurred in this
subgroup.
The researchers noted that like the other pro-
spective cardioversion studies, EMANATE was
underpowered. However, they concluded that their
findings “support the use of apixaban in patients
with AFib undergoing cardioversion.”
Jens Cosedis Nielsen, MD, PhD, of Aarhus University,
Aarhus, Denmark commented, “EMANATE should
be considered an exploratory, not a conclusive trial.
Conducting a 50,000-patient randomized clinical
trial to conclude noninferiority or superiority of one
oral anticoagulant is unrealistic.”
He added, “Randomized trials comparing novel
oral anticoagulants vs vitamin K antagonists pro-
vide us with important data on outcomes around
direct current cardioversion for both treatment
regimens. I think EMANATE was well conducted,
and randomized trials are the best instrument we
have to compare treatments.”
PracticeUpdate Editorial Team
ESC Congress 2017 • PRACTICEUPDATE CONFERENCE SERIES
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