EMANATE: Apixaban reduces stroke risk in patients with AF undergoing cardioversion

Patients with atrial fibrillation who received apixaban before their scheduled cardioversion had a lower risk for stroke compared with warfarin and heparin, according to the EMANATE study presented at the European Society of Cardiology Congress.

Perspective from Kenneth A. Ellenbogen, MD

“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,”

Michael D. Ezekowitz, MD, ChB, DPhil , professor of medicine at Thomas Jefferson University Sidney Kimmel Medical College in Philadelphia and an attending cardiologist at Lankenau Heart Center, Wynnewood, Pennsylvania, and Bryn Mawr Hospital in Pennsylvania, said in a press release. “The EMANATE study points to apixaban as a potential alternative approach.”

Apixaban has not yet been approved by the FDA for use in anticoagulation-naive patients before cardioversion.

The trial included 1,500 patients with AF who were scheduled for cardioversion and were not taking anticoagulants. Patients were assigned to receive apixaban (n = 753; mean age: 65 years; 33% women; mean follow-up, 29 days) or heparin with warfarin (n = 747; mean age: 65 years; 33% women; mean follow-up, 23 days). Those assigned apixaban received a loading dose of 10 mg unless they were at least 80 years old, weighed less than 60 kg or had a serum creatinine level less than 1.5 mg/dL. Patients who met two of the criteria received a loading dose of 5 mg.

Anticoagulants were administered for either 30 days after cardioversion or for a maximum of 90 days if cardioversion was not performed.

No patients in the apixaban group had a stroke vs. six in the standard care group (P = .0164). Systemic embolic outcomes did not occur in either group.

Safety outcomes, including major bleeds and clinically relevant non-major bleeds, were reviewed in a safety population (n = 1,456) who received one or more doses of the study medication. Patients in the apixaban safety group (n = 435) had three major bleeds vs. six in the standard care group (n = 721). Clinically relevant non-major bleeds occurred in 11 patients in the apixaban group and 13 patients in the standard care group.

Imaging was also performed in 840 patients. Echocardiography identified 61 patients with left atrial appendage thrombi present; 30 were assigned apixaban and 31 were assigned standard care. Imaging was repeated after a mean of 37 days for each subgroup. Thrombus was identified in 52% of patients in the apixaban subgroup and 56% patients in the standard care subgroup. No outcome events occurred in either subgroup.

“We believe the findings observed in EMANATE support the use of apixaban in patients with AF undergoing cardioversion,” Ezekowitz said in the presentation. – by Darlene Dobkowski

Reference:

Ezekowitz MD, et al. Late Breaking Clinical Trials 2. Presented at: European Society of Cardiology Congress; August 26-30, 2017; Barcelona, Spain.

Disclosure: The study was funded by Bristol-Myers Squibb and Pfizer. Ezekowitz reports he receives consultant fees from Armetheon, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Janssen Scientific Affairs/Johnson & Johnson, Medtronic, Pfizer, Portola and Sanofi; and grant support from Boehringer Ingelheim, Bristol-Myers Squibb and Pfizer.

Perspective

Kenneth A. Ellenbogen, MD

The results essentially tell us that AF is a common problem. Lots of people have AF, and the more you look for it, the more you find it. This is something we suspected for a long time.

The study shows that apixaban is as effective as IV heparin and warfarin in patients who need cardioversion. That is, you can take a patient and decide you want to cardiovert them today, get them to an echocardiogram and then decide. In the old days, we would have done that and then put them on IV heparin and then warfarin and they’d stay in the hospital 3, 4, 5 days. Nowadays, you can give them a loading dose of apixaban and they do very well.

These findings have implications for clinical practice. No. 1, this is a big study. No. 2, apixaban was every bit as good as heparin plus warfarin if not better in terms of complications. The bottom line is that you can do a transesophageal echocardiography as an outpatient and send them home on pills instead of bringing them into the hospital and having them get IV medication.

This is a definitive study. This has proven positive that a strategy of using novel oral anticoagulants, also known as direct oral anticoagulants, works just as well as anything else.

We will see in the paper what happened to those patients who had clots detected on transesophageal echocardiography and were randomized to heparin vs. apixaban. Both strategies were equivalent, but the numbers were very small and it is hard to make definitive statements about this subgroup.

It is an important study not because we weren’t expecting this outcome, because there have been other studies with some of the other novel oral anticoagulants. It is an important study mostly because it has major financial implications.

Kenneth A. Ellenbogen, MD

Professor and Chair of Cardiology

Virginia Commonwealth University School of Medicine, Richmond

Disclosures: Ellenbogen reports he has no relevant financial disclosures.