Apixaban compared to heparin/vitamin K antagonist in patients with atrial fibrillation scheduled for cardioversion: the EMANATE trial.

Abstract

Aim:

The primary objective was to compare apixaban to heparin/vitamin K antagonist (VKA) in patients with atrial fibrillation (AF) and ≤48 h anticoagulation prior to randomization undergoing cardioversion.

Methods:

One thousand five hundred patients were randomized. The apixaban dose of 5 mg b.i.d. was reduced to 2.5 mg b.i.d. in patients with two of the following: age ≥ 80 years, weight ≤ 60 kg, or serum creatinine ≥ 133 µmol/L. To expedite cardioversion, at the discretion of the investigator, imaging and/or a loading dose of 10 mg (down-titrated to 5 mg) was allowed. The endpoints for efficacy were stroke, systemic embolism (SE), and death. The endpoints for safety were major bleeding and clinically relevant non-major (CRNM) bleeding.

Results:

There were 1038 active and 300 spontaneous cardioversions; 162 patients were not cardioverted. Imaging was performed in 855 patients, and 342 received a loading dose of apixaban. Comparing apixaban to heparin/VKA in the full analysis set, there were 0/753 vs. 6/747 strokes [relative risk (RR) 0; 95% confidence interval (95% CI) 0-0.64; nominal P = 0.015], no SE, and 2 vs. 1 deaths (RR 1.98; 95% CI 0.19-54.00; nominal P > 0.999). In the safety population, there were 3/735 vs. 6/721 major (RR 0.49; 95% CI 0.10-2.07; nominal P = 0.338) and 11 vs. 13 CRNM bleeding events (RR 0.83; 95% CI 0.34-1.89; nominal P = 0.685). On imaging, 60/61 with thrombi continued randomized treatment; all (61) were without outcome events.

Conclusions:

Rates of strokes, systemic emboli, deaths, and bleeds were low for both apixaban and heparin/VKA treated AF patients undergoing cardioversion.

Clinical Trials.gov number:

NCT02100228.

• Authors: Michael D Ezekowitz, Charles V Pollack Jr, Jonathan L Halperin, Richard D England, Sandra VanPelt Nguyen, Judith Spahr, Maria Sudworth, Nilo B Cater, Andrei Breazna, Jonas Oldgren, Paulus Kirchhof
• Journal: European heart journal (Eur Heart J) Vol. 39 Issue 32 Pg. 2959-2971 (08 21 2018) ISSN: 1522-9645 [Electronic] England
• PMID: 29659797 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Pyrazoles
• Pyridones
• Vitamin K
• apixaban
• Heparin

Topics

• Aged
• Anticoagulants (adverse effects, therapeutic use)
• Atrial Fibrillation (complications, diagnostic imaging, mortality, therapy)
• Cause of Death
• Drug Administration Schedule
• Echocardiography, Transesophageal
• Electric Countershock
• Embolism (prevention & control)
• Female
• Hemorrhage (chemically induced, prevention & control)
• Heparin (adverse effects, therapeutic use)
• Humans
• Male
• Middle Aged
• Pyrazoles (administration & dosage, adverse effects, therapeutic use)
• Pyridones (administration & dosage, adverse effects, therapeutic use)
• Stroke (prevention & control)
• Tomography, X-Ray Computed
• Treatment Outcome
• Vitamin K (antagonists & inhibitors)