No strokes were experienced by the apixaban group, compared to 6 in the warfarin arm of the study.
Apixaban, a factor Xa-inhibiting blood thinner, was shown to lower the risk of stroke when compared with warfarin in patients with atrial fibrillation scheduled for elective cardioversion, that were naïve to anticoagulation.
The results of the EMANATE trial, presented at the European Society of Cardiology (ESC) Congress in Barcelona, showed that when compared to warfarin with heparin in patients that had received less than 48 hours of anticoagulation therapy, the risk of stroke was reduced with apixaban (Equilis, Bristol-Myers Squibb).
“The current standard of care for reducing the risk of stroke in the setting of cardioversion is heparin and warfarin, which require monitoring and potential dose adjustment. This can delay performing cardioversion,” Michael D. Ezekowitz (pictured), MB, ChB, DPhil, a professor of medicine in the Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia and Lankenau Medical Center and Bryn Mawr Hospital, said in a statement. “The EMANATE study points to apixaban as a potential alternative approach. Further research is merited to confirm these findings.”
Apixaban was given in an oral 5 mg twice daily dose (or 2.5 mg twice daily for patients that were aged 80 years or older, weighed less than 60 kg, or had serum creatinine levels greater than 1.5 mg/dL), to 753 patients, while 747 patients received the standard treatment of warfarin with heparin. Of the 753 patients on apixaban, a subgroup of 342 patients received an initial 10 or 5 mg loading dose of apixaban if cardioversion was immediate. Rates of systemic embolism, death, major bleeding, and clinically relevant non-major bleeding were all compared.
None of the patients receiving apixaban experienced stroke, compared to 6 in the usual care study arm (p = 0.01), while major bleeds occurred in 3 patients in the apixaban group versus 6 in the usual care group, and non-major bleeding events occurred in 11 and 13 patients, respectively. There were 2 deaths in the apixaban group compared to 1 in the usual care group.
The loading dose subgroup had no strokes or systemic embolic events, 4 clinically relevant non-major bleeds, 1 death, and 1 major bleed.
“Clinicians often prefer cardioversion earlier after a patient is diagnosed with non-valvular atrial fibrillation because the sooner the intervention, the more likely the patient is able to revert back to a regular heart rhythm,” Christoph Koenen, MD, MBA, the VP and development lead for apixaban at Bristol-Myers Squibb, said. “These exploratory data offer preliminary insights into the potential effects of Eliquis in this high-risk clinical setting. Further investigation is needed to better understand anticoagulation for early cardioversion.”
In a follow-up, real-world analysis of 14214 non-vavular atrial fibrillation patients in the US Humana database, the results of EMANATE were supported. The analysis found that patients on apixaban had lower risk of stroke/systemic embolism (hazard ratio [HR]:0.65, 95% confidence interval [CI]: 0.51 to 0.83, p=0.001) and lower rates of major bleeding (HR:0.53, 95% CI: 0.45 to 0.63, p=0.001) compared to warfarin. The follow-up mean duration was 6.3 months for apixaban and 8.3 months for warfarin.
“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,” Ezekowitz said. “We expect these findings will be translated into clinical practice.”