Supplementary Material for: Volume and Characteristics of Intracerebral Hemorrhage with Direct Oral Anticoagulants in Comparison with Warfarin

<i>Background:</i> Patients undergoing anticoagulation therapy often experience intracerebral hemorrhages (ICHs), and warfarin in particular is known to increase hematoma expansion in ICHs, which results in a poor outcome. Recent studies reported that, in comparison with warfarin, direct oral anticoagulants (DOACs) cause fewer ICHs with better functional outcome. However, since it is still unknown whether DOACs are associated with a smaller hematoma volume of ICHs, we aimed to compare the volume, hematoma expansion, and outcomes associated with ICHs treated with DOACs and warfarin. <i>Methods:</i> We performed a prospective multicenter cross-sectional study. The subjects included patients with acute ICHs who received either DOACs or warfarin. We evaluated the clinical characteristics, and measured initial and follow-up ICH volumes. The volume of ICHs and hematoma expansion were compared between the DOAC and warfarin groups. Mortality and modified Rankin score at discharge were evaluated as outcomes. <i>Results:</i> There were 18 patients in the DOAC group and 71 in the warfarin group. The baseline characteristics were similar between the 2 groups. Initial median hematoma volume of ICHs in the DOAC group was significantly lower than that in the warfarin group (6.2 vs. 24.2 mL, respectively; <i>p</i> = 0.04). In cases involving follow-up computed tomography scanning, the median hematoma volume of ICHs at follow-up was lower in the DOAC group than in the warfarin group (initial: DOACs 4.4 vs. warfarin 13.5 mL; follow-up: 5.0 vs. 18.4 mL, respectively; <i>p</i> = 0.05). Further, the hematoma in ICHs associated with DOACs did not expand. Although the mortality of ICHs associated with DOACs (11%) was lower than that associated with warfarin (24%), this difference was not statistically significant. The univariate analysis showed that the anticoagulant type (DOACs vs. warfarin) and sex (male vs. female) were associated with ICH volume. The multivariable linear regression showed that the use of DOACs (compared to warfarin; β: –0.23, <i>p</i> = 0.03) and female sex (compared to male; β: –0.25, <i>p</i> = 0.02) were associated with a small hematoma volume. <i>Conclusions:</i> Based on the results of the present study, in terms of the risks associated with ICHs, the use of DOACs appears to be safer than warfarin for anticoagulation therapy. Further studies are required to validate these findings.

<i>背景:</i> 接受抗凝治疗的患者常并发脑出血（intracerebral hemorrhages, ICH），其中华法林已被证实会增加脑出血患者的血肿扩大风险，进而导致不良预后。近期研究表明，与华法林相比，直接口服抗凝剂（direct oral anticoagulants, DOACs）引发的脑出血更少，且患者功能预后更佳。但目前仍不清楚直接口服抗凝剂是否与更小的脑出血血肿体积相关，因此本研究旨在比较直接口服抗凝剂与华法林治疗相关脑出血的血肿体积、血肿扩大情况及预后结局。<i>方法:</i> 本研究为前瞻性多中心横断面研究。研究对象为接受直接口服抗凝剂或华法林治疗的急性脑出血患者。我们对患者的临床特征进行了评估，并测量了患者初次及随访时的脑出血血肿体积。比较直接口服抗凝剂组与华法林组患者的脑出血血肿体积及血肿扩大情况。以出院时的死亡率及改良Rankin量表评分作为结局指标进行评估。<i>结果:</i> 直接口服抗凝剂组共纳入18例患者，华法林组共纳入71例患者。两组患者的基线特征无显著差异。直接口服抗凝剂组患者的初次脑出血血肿体积中位数显著低于华法林组（分别为6.2 mL与24.2 mL；*p* = 0.04）。在接受随访计算机断层扫描（computed tomography, CT）的病例中，直接口服抗凝剂组患者随访时的脑出血血肿体积中位数仍低于华法林组（初次扫描：直接口服抗凝剂组4.4 mL，华法林组13.5 mL；随访扫描：直接口服抗凝剂组5.0 mL，华法林组18.4 mL；*p* = 0.05）。此外，直接口服抗凝剂相关脑出血患者的血肿未出现扩大。尽管直接口服抗凝剂相关脑出血患者的死亡率（11%）低于华法林组（24%），但该差异未达到统计学显著性。单因素分析显示，抗凝药物类型（直接口服抗凝剂vs华法林）与性别（男性vs女性）与脑出血血肿体积相关。多变量线性回归分析显示，使用直接口服抗凝剂（相较于华法林；β: –0.23，*p* = 0.03）及女性性别（相较于男性；β: –0.25，*p* = 0.02）与更小的脑出血血肿体积独立相关。<i>结论:</i> 基于本研究结果，就脑出血相关风险而言，直接口服抗凝剂用于抗凝治疗似乎比华法林更为安全。未来仍需开展进一步研究以验证本研究发现。