Edoxaban may be as effective as warfarin in preventing strokes or systemic embolism and may also cause less bleeding and cardiovascular death, according to a study published online Nov. 19 in The New England Journal of Medicine and presented simultaneously at the American Heart Association scientific session in Dallas.
“Edoxaban is a more targeted, simpler approach to preventing blood clots,” said lead author Robert P. Giugliano, MD, of Brigham and Women’s Hospital in Boston in a release. “It inhibits the body’s ability to form a clot at a very critical juncture of the clotting pathway and behaves in a more predictable way.”
The Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial enrolled more than 21,000 patients with atrial fibrillation from 1,393 centers in 46 countries between November 2008 and November 2010. Average follow-up time was 2.8 years. The investigators randomized the participants to receive warfarin that was adjusted to an international normalized ratio of 2 to 3 or edoxaban (Daiichi Sankyo). Participants in the edoxaban group received a dose of either 30 mg or 60 mg.
The primary efficacy outcome was time to first ischemic or hemorrhagic stroke, or systemic embolism. The main safety outcome was major bleeding during the course of treatment.
Strokes or systemic embolism occurred in 232 warfarin patients, 182 patients in the high-dose edoxaban group and 253 patients in the low-dose edoxaban group (1.5 percent per year for warfarin, 1.18 percent per year for high-dose edoxaban and 1.61 percent per year for low-dose edoxaban).
The intention-to-treat analysis was more in favor of high-dose edoxaban vs. warfarin (hazard ratio [HR] 0.87) and less in favor of low-dose edoxaban vs. warfarin (HR 1.13).
In terms of safety, the annualized rate of major bleeding was 3.43 percent with warfarin, 2.75 percent with high-dose edoxaban and 1.61 percent with low-dose edoxaban. Cardiovascular death rates were 3.17 percent for warfarin, 2.74 percent for high-dose edoxaban and 2.71 percent for low-dose edoxaban.
Giugliano said the results are promising in the treatment of a common condition.
“Atrial fibrillation is a common problem among the elderly, and as Americans live longer we need safer, yet effective treatments,” Giugliano said. “Once-daily edoxaban may be an important alternative to warfarin.”
Edoxaban is approved for use only in Japan. Daiichi Sankyo provided the funding for the ENGAGE trial.