阿贝西单抗与利伐沙班治疗心房颤动患者的比较
Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation.
作者信息
Ruff Christian T, Patel Siddharth M, Giugliano Robert P, Morrow David A, Hug Bruce, Kuder Julia F, Goodrich Erica L, Chen Shih-Ann, Goodman Shaun G, Joung Boyoung, Kiss Robert G, Spinar Jindrich, Wojakowski Wojciech, Weitz Jeffrey I, Murphy Sabina A, Wiviott Stephen D, Parkar Sanobar, Bloomfield Daniel, Sabatine Marc S
机构信息
From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston (C.T.R., S.M.P., R.P.G., D.A.M., J.F.K., E.L.G., S.A.M., S.D.W., M.S.S.); Anthos Therapeutics, Cambridge, MA (B.H., S.P., D.B.); the Heart Rhythm Center, Taipei Veterans General Hospital and Cardiovascular Center, Taipei, Taiwan (S.-A.C.); Taichung Veterans Hospital, Taichung, Taiwan (S.-A.C.); National Yang Ming Chiao Tung University, Hsinchu, Taiwan (S.-A.C.); National Chung Hsing University, Taichung, Taiwan (S.-A.C.); St. Michael's Hospital, Unity Health Toronto, Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto (S.G.G.); Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada (S.G.G.); the Division of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea (B.J.); the Department of Cardiology, Central Hospital of Northern Pest-Military Hospital, Budapest, Hungary (R.G.K.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (R.G.K.); the Internal Cardiology Department, St. Ann University Hospital and Masaryk University, Brno, Czech Republic (J.S.); the Department of Cardiology and Structural Heart Diseases, Medical University of Silesia, Katowice, Poland (W.W.); the Departments of Medicine and of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada (J.W.); and the Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada (J.W.).
出版信息
N Engl J Med. 2025 Jan 23;392(4):361-371. doi: 10.1056/NEJMoa2406674.
BACKGROUND
Abelacimab is a fully human monoclonal antibody that binds to the inactive form of factor XI and blocks its activation. The safety of abelacimab as compared with a direct oral anticoagulant in patients with atrial fibrillation is unknown.
METHODS
Patients with atrial fibrillation and a moderate-to-high risk of stroke were randomly assigned, in a 1:1:1 ratio, to receive subcutaneous injection of abelacimab (150 mg or 90 mg once monthly) administered in a blinded fashion or oral rivaroxaban (20 mg once daily) administered in an open-label fashion. The primary end point was major or clinically relevant nonmajor bleeding.
RESULTS
A total of 1287 patients underwent randomization; the median age was 74 years, and 44% were women. At 3 months, the median reduction in free factor XI levels with abelacimab at a dose of 150 mg was 99% (interquartile range, 98 to 99) and with abelacimab at a dose of 90 mg was 97% (interquartile range, 51 to 99). The trial was stopped early on the recommendation of the independent data monitoring committee because of a greater-than-anticipated reduction in bleeding events with abelacimab. The incidence rate of major or clinically relevant nonmajor bleeding was 3.2 events per 100 person-years with 150-mg abelacimab and 2.6 events per 100 person-years with 90-mg abelacimab, as compared with 8.4 events per 100 person-years with rivaroxaban (hazard ratio for 150-mg abelacimab vs. rivaroxaban, 0.38 [95% confidence interval {CI}, 0.24 to 0.60]; hazard ratio for 90-mg abelacimab vs. rivaroxaban, 0.31 [95% CI, 0.19 to 0.51]; P<0.001 for both comparisons). The incidence and severity of adverse events appeared to be similar in the three groups.
CONCLUSIONS
Among patients with atrial fibrillation who were at moderate-to-high risk for stroke, treatment with abelacimab resulted in markedly lower levels of free factor XI and fewer bleeding events than treatment with rivaroxaban. (Funded by Anthos Therapeutics; AZALEA-TIMI 71 ClinicalTrials.gov number, NCT04755283.).
背景
阿贝西单抗是一种全人源单克隆抗体，可与因子XI的无活性形式结合并阻止其激活。在心房颤动患者中，与直接口服抗凝剂相比，阿贝西单抗的安全性尚不清楚。
方法
将有中度至高度卒中风险的心房颤动患者按1:1:1的比例随机分配，以盲法皮下注射阿贝西单抗（150 mg或90 mg，每月一次）或开放标签口服利伐沙班（20 mg，每日一次）。主要终点是大出血或临床相关非大出血。
结果
共有1287例患者进行了随机分组；中位年龄为74岁，44%为女性。3个月时，150 mg剂量阿贝西单抗组游离因子XI水平的中位降低率为99%（四分位间距，98%至99%），90 mg剂量阿贝西单抗组为97%（四分位间距，51%至99%）。由于阿贝西单抗治疗导致的出血事件减少幅度大于预期，该试验在独立数据监测委员会的建议下提前终止。150 mg阿贝西单抗组大出血或临床相关非大出血的发生率为每100人年3.2次事件，90 mg阿贝西单抗组为每100人年2.6次事件，而利伐沙班组为每100人年8.4次事件（150 mg阿贝西单抗与利伐沙班相比的风险比为0.38[95%置信区间{CI}，0.24至0.60]；90 mg阿贝西单抗与利伐沙班相比的风险比为0.31[95%CI，0.19至0.51]；两组比较P<0.001）。三组不良事件的发生率和严重程度似乎相似。
结论
在中度至高度卒中风险的心房颤动患者中，与利伐沙班治疗相比，阿贝西单抗治疗导致游离因子XI水平显著降低，出血事件减少。（由Anthos Therapeutics资助；AZALEA-TIMI 71临床试验注册号，NCT04755283。）
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