Data from the EMANATE trial, which was presented at a Hot Line session of the European Society of Cardiology (ESC) congress (26–30 August, Barcelona, Spain), indicate that the risk of stroke is significantly lower in atrial fibrillation patients who are scheduled to undergo cardioversion and are receiving apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) than those receiving warfarin.
The purpose of the EMANATE trial was to compare the rates of stroke and bleeding with apixaban versus warfarin with heparin in anticoagulation-naïve (defined as having received less than 48 hours of anticoagulation therapy) patients scheduled for elective cardioversion of predominately new onset non-valvular atrial fibrillation.
In this multicentre, prospective, randomised, open-label trial, 1,500 patients with atrial fibrillation were randomised to receive apixaban or to receive parenteral heparin with warfarin. Apixaban was administered orally at a dose of 5mg twice a day (or 2.5mg 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 10mg or 5mg loading dose of apixaban (for study doses of 5mg and 2.5mg, respectively) if the cardioversion was immediate. Rates of stroke, systemic embolism, death, major bleeding, and clinically relevant non-major bleeding were compared between the two groups.
Patients treated with apixaban had fewer strokes and similar bleeding to those receiving usual care. There were no strokes in the 753 patients treated with apixaban compared to six strokes in the 747 receiving usual care (p=0.01). There were no systemic embolic events in either group. Major bleeds occurred in three and six patients in the apixaban and usual care groups, respectively, while clinically significant non-major bleeding occurred in 11 and 13 patients. There were two deaths in the apixaban group and one in the heparin/warfarin group.
Out of 753 patients in the apixaban group, 342 received a loading dose. In this subgroup there were no strokes or systemic embolic events, one death, one major bleed, and four clinically relevant non-major bleeds.
Michael Ezekowitz (Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, USA), says: “In patients with atrial fibrillation undergoing cardioversion, apixaban with or without a loading dose was safe, resulting in few bleeding events and less strokes than conventional anticoagulant therapy. We expect these findings will be translated into clinical practice.”