Phase IV EMANATE trial of Eliquis (apixaban) reports data for patients with non-valvular atrial fibrillation (NVAF) undergoing cardioversion-BMS + Pfizer.

Bristol-Myers Squibb Company and Pfizer Inc. presented findings from EMANATE (Eliquis evaluated in acute cardioversion coMpared to usuAl treatmeNts for AnTicoagulation in subjEcts with NVAF), a Phase IV clinical trial. This descriptive, randomized, open-label trial explored the safety and efficacy of apixaban 5 mg twice daily (2.5 mg lower dose when two of the following were present: age more than 80 years, weight less than 60 kg, or serum creatinine more than 1.5 mg/dL vs. standard of care (parenteral heparin and/or vitamin K antagonist). The outcomes measured in this study were the occurrence of acute stroke, systemic embolism, major bleeding, clinically relevant non-major bleeding and all-cause death in non-valvular atrial fibrillation patients undergoing cardioversion. This is an investigational use for Eliquis. Eliquis is not FDA-approved for the reduction of stroke in NVAF patients undergoing cardioversion .

The EMANATE study randomized patients with recently diagnosed NVAF who were anticoagulation-na�ve (defined as having received less than 48 hours of anticoagulation) to either apixaban or standard of care (warfarin with or without heparin). The study protocol encouraged the use of image guidance according to the guidelines to determine the absence of a clot in the heart, allowing earlier cardioversion, or anticoagulation for a minimum of three weeks before cardioversion. Anticoagulation was administered from randomization until 30 days after cardioversion. If cardioversion was not performed, anticoagulation was to be administered for a maximum of 90 days. The apixaban dose was 5 mg twice daily (or dose reduced per standard criteria). If the imaging study showed no clot in the heart, five doses of apixaban were administered to achieve steady-state blood levels before cardioversion. Alternatively, if no clot was detected, an immediate cardioversion could be undertaken following a single 10 mg loading dose of apixaban (or dose reduced per standard criteria) administered at least two hours before cardioversion, followed by a maintenance regimen. The loading dose enabled patients to quickly attain steady state-like concentrations of anticoagulation, allowing for earlier cardioversion.

Results showed that, in the intent-to-treat (ITT) population (n=1500; Eliquis n=753, heparin/VKA n=747), there were no strokes or systemic emboli in the Eliquis group compared to six strokes (one hemorrhagic and five ischemic) and no systemic emboli in the standard of care group. In the safety analysis population (n=1436; Eliquis n=735, heparin/VKA n=721), which included all patients receiving one dose of study drug, there were numerically fewer major bleeding events in the apixaban treatment group (n=3) than those randomly assigned to standard of care (n=6), and numerically fewer clinically relevant non-major bleeding events in the apixaban treatment group (n=11) than those randomly assigned to standard of care (n=13). It is important to note that Eliquis increases the risk of bleeding and can cause serious, potentially fatal, bleeding. There were two deaths in the Eliquis group (one due to acute alcoholic hepatitis prior to dosing, and one due to complications related to perforation of the colon) and one in the standard of care group.