April 16, 2018
By Will Boggs MD
NEW YORK (Reuters Health) - Apixaban is safe and effective for anticoagulation in patients with atrial fibrillation (AF) scheduled for cardioversion, according to results from the EMANATE trial.
These findings "will allow clinicians to safely cardiovert patients soon after they present with AF and thus avoid admission to the hospital," Dr. Michael D. Ezekowitz from Sidney Kimmel Medical College at Thomas Jefferson University, in Philadelphia, told Reuters Health by email.
Apixaban, a direct inhibitor of factor Xa, reduces stroke, systemic embolism, major bleeding and death in patients with AF, compared with warfarin. But it has not been evaluated previously in patients undergoing cardioversion, Dr. Ezekowitz and colleagues note in the European Heart Journal, online April 6.
They assessed these outcomes in 1,500 patients with AF undergoing cardioversion during anticoagulation with either apixaban or a conventional heparin/vitamin K antagonist (VKA) regimen who had no more than 48 hours of anticoagulation prior to randomization.
Stroke rates were very low in both groups (0/753 with apixaban and 6/747 with heparin/VKA), and there were no systematic embolic events in either group.
There were two deaths in the apixaban arm and one in the heparin/VKA arm (0.27% vs. 0.13%, P >0.9999).
The treatment groups did not differ significantly in the rates of major bleeding or clinically relevant non-major bleeding events (0.41% and 1.5%, respectively, for apixaban, vs. 0.83% and 1.8% for heparin/VKA).
Sixty of 61 patients with imaging-identified thrombi continued randomized treatment, all without events.
The mean time to first active cardioversion in the apixaban group was 3.3 days after the loading dose in those undergoing imaging, 4.1 days after the loading dose in those without imaging and 25.7 days on average in those who did not receive a loading dose.
The mean time from first dose to cardioversion was 17.8 days in the heparin/VKA group.
The researchers note that the trial was exploratory, and that adequate power for a noninferiority trial would have required a sample size of approximately 48,000 patients.
"Using the single loading dose of apixaban allowed cardioversion 2 hours after oral administration and did so without any strokes or systemic embolism and only one major bleed," Dr. Ezekowitz said. "Apixaban is a safe and simpler means of preventing thromboembolic events in patients undergoing elective cardioversion."
Dr. Jan Steffel from University Heart Center Zurich in Switzerland, who co-authored the 2018 European Heart Rhythm Association Practical Guide on the use of non-VKA oral anticoagulants (NOACs) in patients with AF, told Reuters Health by email, "This is the last of the 3 cardioversion studies for Factor Xa inhibitors (after X-Vert for Rivaroxaban and ENSURE-AF for Edoxaban). We need to keep in mind that all of them were, individually, underpowered for efficacy. However, in totality (together with the many cardioversions performed with Dabigatran in Re-Ly), the message is clear: we can safely use NOACs also in this setting."
He advised, "To replicate the positive findings, stick to the settings of the studies: If AF >48 hours (likely even when >24 hours): Perform transesophageal echocardiography (TEE) to rule out left atrial appendage (LAA) clot or anticoagulate for 3 weeks prior to cardioversion."
Pfizer and Bristol-Myers Squibb supported the EMANATE trial and employed several of the authors. Dr. Ezekowitz also reports financial ties to the companies.
Eur Heart J 2018.
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