日本济生会熊本医院Ken Okumura团队研究了小剂量依度沙班治疗高龄房颤患者的疗效。2020年8月30日，该研究发表在《新英格兰医学杂志》上。

出于对大出血的担忧，在高龄房颤患者中实施适当的口服抗凝治疗以预防中风极具挑战性。

研究组进行了一项临床3期、多中心、随机、双盲、安慰剂对照、事件驱动试验，在日本招募了984名80岁以上的老年非瓣膜性房颤患者，按1：1随机分配，其中492例接受每日15mg的依度沙班治疗，492例接受安慰剂治疗。根据国际血栓形成和止血协会的定义，主要疗效终点是中风或全身性栓塞的综合症状，主要安全终点是大出血。

共有681名患者完成了该试验，其中303名终止了试验，两组间终止试验的患者人数相似。依度沙班组中风或全身性栓塞的年发生率为2.3％，显著低于安慰剂组（6.7％）；依度沙班组大出血发生率为3.3％，安慰剂组为1.8％，组间差异不大。依度沙班组的胃肠道出血事件明显多于安慰剂组。两组间的全因死亡率差异无统计学意义。

总之，对于不耐受标准剂量口服抗凝剂的高龄非瓣膜性房颤患者，每日一次15mg依度沙班在预防中风或全身性栓塞方面优于安慰剂。

附：英文原文

Title: Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation | NEJM

Author: Ken Okumura, M.D., Ph.D.,, Masaharu Akao, M.D., Ph.D.,, Tetsuro Yoshida, M.D., Ph.D.,, Masahito Kawata, M.D., Ph.D.,, Osamu Okazaki, M.D., Ph.D.,, Shintaro Akashi, M.D., Ph.D.,, Kenichi Eshima, M.D., Ph.D.,, Kimihiko Tanizawa, Ph.D.,, Masayuki Fukuzawa, M.S.,, Takuya Hayashi, M.S.,, Masahiro Akishita, M.D., Ph.D.,, Gregory Y.H. Lip, M.D.,, and Takeshi Yamashita, M.D., Ph.D.

Issue&Volume: 2020-08-30

Abstract: Abstract

Background

Implementation of appropriate oral anticoagulant treatment for the prevention of stroke in very elderly patients with atrial fibrillation is challenging because of concerns regarding bleeding.

Methods

We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled, event-driven trial to compare a once-daily 15-mg dose of edoxaban with placebo in elderly Japanese patients (≥80 years of age) with nonvalvular atrial fibrillation who were not considered to be appropriate candidates for oral anticoagulant therapy at doses approved for stroke prevention. The primary efficacy end point was the composite of stroke or systemic embolism, and the primary safety end point was major bleeding according to the definition of the International Society on Thrombosis and Haemostasis.

Results

A total of 984 patients were randomly assigned in a 1:1 ratio to receive a daily dose of 15 mg of edoxaban (492 patients) or placebo (492 patients). A total of 681 patients completed the trial, and 303 discontinued (158 withdrew, 135 died, and 10 had other reasons); the numbers of patients who discontinued the trial were similar in the two groups. The annualized rate of stroke or systemic embolism was 2.3% in the edoxaban group and 6.7% in the placebo group (hazard ratio, 0.34; 95% confidence interval [CI], 0.19 to 0.61; P<0.001), and the annualized rate of major bleeding was 3.3% in the edoxaban group and 1.8% in the placebo group (hazard ratio, 1.87; 95% CI, 0.90 to 3.89; P=0.09). There were substantially more events of gastrointestinal bleeding in the edoxaban group than in the placebo group. There was no substantial between-group difference in death from any cause (9.9% in the edoxaban group and 10.2% in the placebo group; hazard ratio, 0.97; 95% CI, 0.69 to 1.36).

Conclusions

In very elderly Japanese patients with nonvalvular atrial fibrillation who were not appropriate candidates for standard doses of oral anticoagulants, a once-daily 15-mg dose of edoxaban was superior to placebo in preventing stroke or systemic embolism and did not result in a significantly higher incidence of major bleeding than placebo.

DOI: 10.1056/NEJMoa2012883

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2012883