Practice Update - ESC Congress 2017

Apixaban Lowers Stroke Risk in Patients Undergoing Cardioversion for Atrial Fibrillation – EMANATE Trial Apixaban has been shown to lower the risk of stroke vs warfarin in anticoagulation-naïve patients with atrial fibrillation scheduled for elective cardioversion. Rates of bleeding were similar between the two groups. This conclusion, based on results of the multicenter, prospective, randomized, open-label Eliquis evaluated in acute cardioversion coMpared to usuAl treatmeNts for AnTicoagulation in subjects with NVAF (EMANATE) trial, was presented at the 2017 European Society of Cardiology (ESC) Congress, from August 26–30.

M ichael D. Ezekowitz, MD, PhD, of the Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, explained that atrial fibrillation is the most com- mon heart rhythm disorder and is associated with increased risks of death and stroke. Cardioversion – restoring andmaintaining the heart’s normal rhythm – is an integral part of management, as are antico- agulants, to prevent strokes. Apixaban blocks the action of the clotting factor Xa and like other blood thinners, lowers the chance of blood clots forming. Other blood thinners include heparin and warfarin. While blood thinners pre- vent clotting and decrease the chance of having a stroke, they also increase the risk of bleeding. Patients scheduled for cardioversion for atrial fibrillation have traditionally received heparin and/ or warfarin to reduce their risk of stroke. Post hoc analyses of cardioversion in the RE-LY, ARISTOTLE, ROCKET-AF, and ENGAGE-AF trials found low event rates. These trials were limited, however, by pro- longed periods of precardioversion anticoagulation. To evaluate more immediate cardioversion, pro- spective trials comparing rivaroxaban (x-VeRT) and edoxaban (ENSURE-AF) vs heparin/vitamin K antag- onism in patients undergoing cardioversion found comparable efficacy and safety with low event rates.

the following conditions were met: age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL). At the discretion of the local investigator, patients could also receive an initial 10 mg or 5 mg loading dose of apixaban (for study doses of 5 mg and 2.5mg, respectively) if cardioversion was immediate. Rates of stroke, systemic embolism, death, major bleeding, and clinically relevant nonmajor bleeding were compared between the two groups. Patients treated with apixaban suffered fewer strokes and similar bleeding to those receiving usual care. No strokes occurred in the 753 patients treated with apixaban vs six strokes in the 747 patients who received usual care (P = .01). No systemic embolic events occurred in either group. Major bleeds occurred in three and six patients in the apixaban and usual care groups, respectively. Clinically significant nonmajor bleeding occurred in 11 and 13 patients, respectively. Two deaths occurred in the apixaban group and one in the heparin/warfarin group. Of 753 patients in the apixaban group, 342 received a loading dose. No strokes or systemic embolic events, one death, one major bleed, and four clin- ically relevant nonmajor bleeds occurred in this subgroup. The researchers noted that like the other pro- spective cardioversion studies, EMANATE was underpowered. However, they concluded that their findings “support the use of apixaban in patients with AFib undergoing cardioversion.” Jens Cosedis Nielsen, MD, PhD, of Aarhus University, Aarhus, Denmark commented, “EMANATE should be considered an exploratory, not a conclusive trial. Conducting a 50,000-patient randomized clinical trial to conclude noninferiority or superiority of one oral anticoagulant is unrealistic.” He added, “Randomized trials comparing novel oral anticoagulants vs vitamin K antagonists pro- vide us with important data on outcomes around direct current cardioversion for both treatment regimens. I think EMANATE was well conducted, and randomized trials are the best instrument we have to compare treatments.”

Dr. Michael D. Ezekowitz

Apixaban has not been tested prospectively in patients under- going cardioversion. The purpose of EMANATE was to compare rates of stroke and bleeding with apixaban vs warfarin with heparin in anti- coagulation-naïve (<48 h of anticoagulation therapy) patients scheduled for elective cardiover- sion of predominantly new-onset non-valvular atrial fibrillation. The study included 1500 patients with atrial fibrillation who were randomized to apixaban or par- enteral heparin with warfarin. Apixaban was administered orally at a dose of 5 mg twice a day (or 2.5 mg twice a day when two of

PracticeUpdate Editorial Team

ESC Congress 2017 • PRACTICEUPDATE CONFERENCE SERIES 11