心房細動においてエドキサバンのワルファリンに対する非劣性が認められた（LBCT 5/Abstract: 15039）

ENGAGE AF-TIMI 48：心房細動患者の脳卒中予防においてエドキサバンはワルファリンよりも有効で安全であることが明らかにされた
ENGAGE AF-TIMI 48: Edoxaban found to be as effective and safer than warfarin for stroke prevention in patients with atrial fibrillation
新薬エドキサバンは抗凝固薬ワルファリンよりも脳卒中予防において有効であり安全であるとのlate-breaking clinical trialの結果が2013年American Heart Association学会で発表され同時にNew England Journal of Medicineに掲載された。ENGAGE AF-TIMI 48トライアルは46か国1,400の病院の心房細動患者21,000人超を対象とした。参加者はエドキサバン1日60mg（高用量）、エドキサバン1日 30mg（低用量）またはワルファリンを投与される群に無作為に割り付けられた。脳卒中予防においてエドキサバンはワルファリンと同等に有効であり、出血リスクおよび心血管疾患関連死のリスクは有意に低かった。ワルファリンと比較し、重大な出血は高用量エドキサバン群において20%低く、低用量エドキサバン群では53%低かった。ワルファリンと比較し、高用量エドキサバン群では心血管死が14%少なく、低用量エドキサバン群では15%少なかった。エドキサ バンは現在日本において、整形外科手術を施行される深部静脈血栓症のリスクのある患者に対してのみ承認されている。
Full Text

A new drug, Edoxaban, was as effective in preventing strokes and safer than the anticoagulant warfarin in patients with atrial fibrillation, according to a late-breaking clinical trial presented at the American Heart Association's Scientific Sessions 2013 and simultaneously published in the New England Journal of Medicine. 

The ENGAGE AF-TIMI 48 Trial included more than 21,000 atrial fibrillation patients in 46 countries in 1,400 hospitals. Participants were randomly assigned to receive a high dose of edoxaban at 60 mg per day, a low dose of edoxaban at 30 mg per day or warfarin.

Edoxaban performed as well as warfarin in preventing strokes, while significantly reducing the risk of bleeding and cardiovascular disease-related death.

  • Compared with warfarin, major bleeding was 20 percent lower among patients taking the high dose of edoxaban and 53 percent lower among those taking the lose dose.
  • Compared with warfarin, the high dose of edoxaban was associated with a 14 percent reduction in cardiovascular death; the low dose was associated with a 15 percent reduction.

Instead of depleting the body's clotting proteins like warfarin, edoxaban singles out one key clotting protein called Xa, to prevent clots.

"Edoxaban is a more targeted, simpler approach to preventing blood clots," said Robert P. Giugliano, M.D., lead author of the study and a researcher and physician at Brigham and Women's Hospital in Boston. "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."

During the trial, the assigned dose of edoxaban was reduced for some patients based on their kidney function, body weight or because they were taking certain medications. Some patients who started out on the 60 mg of edoxaban were lowered to 30 mg, and some who began the study at 30 mg of edoxaban were switched to 15 mg.

Researchers will study edoxaban's side effects, which patient populations may benefit most, develop standards for monitoring dosing and determine how best to quickly reverse its effects if needed in an emergency. Edoxaban is currently approved for use only in Japan in patients undergoing orthopedic surgery who are at risk for deep vein thrombosis.

"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."

Co-authors are C.T. Ruff, M.D.; E. Braunwald, M.D.; S.A. Murphy; S.D. Wiviott, M.D.; J.L. Halperin, M.D.; A.L. Waldo, M.D.; M.D. Ezekowitz, M.D.; J.I. Weitz, M.D.; J. Spinar, M.D.; W. Ruzyllo, M.D.; M. Ruda, M.D.; Y. Korestune, M.D.; J.M. Betcher; M. Shi; L.T. Grip; S.P. Patel; I. Patel, M.D.; J.J. Hanyok; M. Mercuri; and E.M. Antman, M.D., on behalf of the ENGAGE AF-TIME 48 Investigators.  Disclosures

Daiichi-Sankyo funded the study.