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
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.).
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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