Use of apixaban prior to cardioversion reduces risk of stroke

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According to the results of the EMANATE trial, patients with atrial fibrillation (AF) who receive apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) before undergoing elective cardioversion of patients with atrial fibrillation to normal sinus rhythm have a lower risk of stroke than those who receive heparin or warfarin prior to cardioversion. The study, which was presented at the European Society of Cardiology (ESC) congress (26–30 August, Barcelona, Spain), also demonstrated similar rates of bleeding between the two groups.

Anticoagulation is given prior to cardioversion to prevent stroke and systemic embolism. This is typically in the form of heparin or warfarin. Both have limitations because the former has to be given by injection while the latter may take a week or much longer to have a therapeutic effect. Apixaban—a non-vitamin K antagonist oral anticoagulant that has a rapid onset of action—may provide an alternative, but it has not been prospectively tested in this setting.

Speaking at the ESC congress, Principal investigator Michael Ezekowitz, (Thomas Jefferson University, Philadelphia, USA) outlined the goals of EMANATE, as firstly “to prospectively compare the outcomes of stroke, systemic embolisation, major bleeding, and clinically relevant non-major bleeding in patients with less than 48 hours anticoagulation (for this episode of AF) who were randomised to apixaban or heparin/warfarin in an open-label trial with blinded endpoint adjudication”.

“In addition,” he continued, “we wanted to gain more insight into the role of image guidance as it pertains to cardioversion, and also interestingly to assess the value of a loading dose of apixaban in patients who were being rapidly transitioned to cardioversion.”

Participants (1,500) in the multicentre study were anticoagulation-naïve (less than 48 hours of anticoagulation therapy; 61 % received no anticoagulation ) patients who were scheduled for elective cardioversion of predominately new onset non-valvular AF.

The trial found that those treated with apixaban had fewer strokes and similar bleeding to patients receiving usual care, with no systemic embolic events in either group. There were no strokes in the 753 patients treated with apixaban compared to six strokes in the 747 receiving usual care. Major bleeds occurred in three patients, and clinically significant non-major bleeding in 11 patients receiving apixaban. Of those receiving usual care, six had a major bleed, with 13 experiencing a clinically significant non-major bleed. There were two deaths in the apixaban group and one in the heparin/warfarin group.

Among 342 patients in the apixaban group who received a loading dose there were no strokes or systemic embolic events, one death, one major bleed, and four clinically relevant non-major bleeds. In the patients that were imaged, there was resolution of thrombi in 52% of the apixaban group and 56% of the heparin group.

When asked whether the low event rate in the study was due to patient selection or the length of follow-up period, Ezekowitz said: “I think we have made tremendous progress with regards to anticoagulation in the past 10 years, and the novel agents are particularly successful. It basically means that anticoagulation works in patients undergoing cardioversion.”

But Jens Cosedis Nielsen (Aarhus University Hospital, Denmark) said that the trial should be considered “an exploratory trial and not a conclusive trial”. He pointed out: “There were statistically significantly fewer strokes in the apixaban group than the other group. But looking into the other endpoints,; there were no statistically significant differences. And, taking into account the low number of events, we have to be very careful interpreting any statistical comparisons done in this trial.”

Ezekowitz acknowledged that, like other prospective cardioversion trials, the study was underpowered, but, he added, “we believe the findings observed in EMANATE support the use of apixaban in patients with AF undergoing cardioversion”.

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