Department of Neurology and Anesthesiology & Critical Care Medicine, Johns Hopkins Hospital, Baltimore, MD, USA.
TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
J Clin Neurosci. 2021 Apr;86:294-300. doi: 10.1016/j.jocn.2020.10.036. Epub 2021 Jan 12.
Intracranial hemorrhage (ICH) is a known risk of oral anticoagulation; delineating ICH attributes may provide nuanced guidance regarding atrial fibrillation management. We evaluated ICH characteristics and outcomes from Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48), a randomized trial that compared two edoxaban regimens (higher-dose edoxaban regimen 60/30 mg (HDER), lower-dose edoxaban regimen 30/15 mg (LDER)) with warfarin in patients with atrial fibrillation. Patients who suffered ICH vs those who did not were compared and independent predictors of ICH were calculated. We also assessed ICH subtype and etiology. Of 21,105 randomized patients, 322 (1.53%) had ≥ 1 ICH for a total of 368 events. Intraparenchymal hemorrhage (HDER: HR 0.52 [95% CI 0.35-0.77], LDER: HR 0.22 [0.13-0.38]) and subdural hematoma (HDER: HR 0.29 [0.15-0.55], LDER: HR 0.26 [0.13-0.50]) were lower with both HDER and LDER vs warfarin. Subarachnoid hemorrhage frequency was similar in the HDER vs warfarin groups but lower in LDER. Compared to warfarin, edoxaban was associated with lower risk of spontaneous ICH (HDER: HR 0.47 [0.31-0.69], LDER: HR 0.34 [0.22-0.53]) and traumatic ICH (HDER: HR 0.32 [0.17-0.61], LDER: HR 0.31 [0.16-0.59]). In multivariable analysis, randomization to warfarin, increased age, and risk of falling remained independent predictors of ICH. In ENGAGE AF-TIMI 48, ICH was decreased in edoxaban-treated patients compared to warfarin-treated patients, including ICH of both spontaneous and traumatic causes. Both edoxaban regimens lowered intraparenchymal and subdural hemorrhages compared to warfarin. Patient characteristics and medical history may help guide anticoagulation management.
颅内出血 (ICH) 是口服抗凝的已知风险；描述 ICH 特征可能为房颤管理提供细微差别指导。我们评估了房颤血栓栓塞预防的新型口服抗凝剂（ENGAGE AF-TIMI 48）试验中 ICH 特征和结局，这是一项随机试验，比较了两种依度沙班治疗方案（高剂量依度沙班 60/30mg[HDER]、低剂量依度沙班 30/15mg[LDER]）与华法林在房颤患者中的疗效。比较了发生 ICH 与未发生 ICH 的患者，并计算了 ICH 的独立预测因素。我们还评估了 ICH 亚型和病因。在 21105 名随机患者中，322 名（1.53%）至少发生了 1 次 ICH，共发生 368 例事件。与华法林相比，HDER（HR 0.52 [95%CI 0.35-0.77]）和 LDER（HR 0.22 [0.13-0.38]）的脑实质出血和硬膜下血肿（HDER：HR 0.29 [0.15-0.55]，LDER：HR 0.26 [0.13-0.50]）均降低。HDER 组与华法林组蛛网膜下腔出血频率相似，但 LDER 组较低。与华法林相比，依度沙班与自发性 ICH 风险降低相关（HDER：HR 0.47 [0.31-0.69]，LDER：HR 0.34 [0.22-0.53]）和外伤性 ICH（HDER：HR 0.32 [0.17-0.61]，LDER：HR 0.31 [0.16-0.59]）。多变量分析显示，随机分组至华法林、年龄增加和跌倒风险仍是 ICH 的独立预测因素。在 ENGAGE AF-TIMI 48 中，与华法林治疗患者相比，依度沙班治疗患者的 ICH 减少，包括自发性和外伤性ICH。与华法林相比，两种依度沙班方案均降低了脑实质出血和硬膜下出血。患者特征和病史可能有助于指导抗凝管理。
