From the Department of Neurology (S.T.G., J.B.K., J.A.S., M.I.S., M. Hagen, R.U.K., S. Schwab, H.B.H.), University of Erlangen-Nuremberg, Germany.
Department of Neurology (M.E., K.G.H., J. Sobesky, S.Z.), Charité-Universitätsmedizin Berlin, Germany.
Stroke. 2019 Jun;50(6):1392-1402. doi: 10.1161/STROKEAHA.118.023492. Epub 2019 May 16.
Background and Purpose- Given inconclusive studies, it is debated whether clinical and imaging characteristics, as well as functional outcome, differ among patients with intracerebral hemorrhage (ICH) related to vitamin K antagonists (VKA) versus non-vitamin K antagonist (NOAC)-related ICH. Notably, clinical characteristics according to different NOAC agents and dosages are not established. Methods- Multicenter observational cohort study integrating individual patient data of 1328 patients with oral anticoagulation-associated ICH, including 190 NOAC-related ICH patients, recruited from 2011 to 2015 at 19 tertiary centers across Germany. Imaging, clinical characteristics, and 3-months modified Rankin Scale (mRS) outcomes were compared in NOAC- versus VKA-related ICH patients. Propensity score matching was conducted to adjust for clinically relevant differences in baseline parameters. Subgroup analyses were performed regarding NOAC agent, dosing and present clinically relevant anticoagulatory activity (last intake <12h/24h or NOAC level >30 ng/mL). Results- Despite older age in NOAC patients, there were no relevant differences in clinical and hematoma characteristics between NOAC- and VKA-related ICH regarding baseline hematoma volume (median [interquartile range]: NOAC, 14.7 [5.1-42.3] mL versus VKA, 16.4 [5.8-40.6] mL; P=0.33), rate of hematoma expansion (NOAC, 49/146 [33.6%] versus VKA, 235/688 [34.2%]; P=0.89), and the proportion of patients with unfavorable outcome at 3 months (mRS, 4-6: NOAC 126/179 [70.4%] versus VKA 473/682 [69.4%]; P=0.79). Subgroup analyses revealed that NOAC patients with clinically relevant anticoagulatory effect had higher rates of intraventricular hemorrhage (n/N [%]: present 52/109 [47.7%] versus absent 9/35 [25.7%]; P=0.022) and hematoma expansion (present 35/90 [38.9%] versus absent 5/30 [16.7%]; P=0.040), whereas type of NOAC agent or different NOAC-dosing regimens did not result in relevant differences in imaging characteristics or outcome. Conclusions- If effectively anticoagulated, there are no differences in hematoma characteristics and functional outcome among patients with NOAC- or VKA-related ICH. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT03093233.
背景与目的- 鉴于研究结果不一致,目前仍存在争议,即与维生素 K 拮抗剂(VKA)相关的脑出血(ICH)患者与非维生素 K 拮抗剂(NOAC)相关的 ICH 患者之间,其临床和影像学特征以及功能结局是否存在差异。值得注意的是,不同的 NOAC 药物及其剂量的临床特征尚未明确。方法- 这是一项多中心观察性队列研究,整合了 2011 年至 2015 年间德国 19 家三级中心的 1328 例口服抗凝药物相关 ICH 患者的个体患者数据,包括 190 例与 NOAC 相关的 ICH 患者。比较了 NOAC 相关 ICH 患者与 VKA 相关 ICH 患者的影像学、临床特征和 3 个月改良 Rankin 量表(mRS)结局。采用倾向评分匹配法调整基线参数的临床相关差异。针对 NOAC 药物、剂量和当前临床相关抗凝活性(最后一次服药时间<12 小时/24 小时或 NOAC 水平>30ng/mL)进行亚组分析。结果- 尽管 NOAC 患者年龄较大,但在 NOAC 相关 ICH 患者与 VKA 相关 ICH 患者之间,基线血肿体积(NOAC:14.7[5.1-42.3]mL;VKA:16.4[5.8-40.6]mL;P=0.33)、血肿扩大率(NOAC:49/146[33.6%];VKA:235/688[34.2%];P=0.89)和 3 个月时预后不良的患者比例(mRS,4-6:NOAC:126/179[70.4%];VKA:473/682[69.4%];P=0.79)方面均无明显差异。亚组分析显示,具有临床相关抗凝作用的 NOAC 患者发生脑室内出血(n/N[%]:有 52/109[47.7%];无 9/35[25.7%];P=0.022)和血肿扩大(有 35/90[38.9%];无 5/30[16.7%];P=0.040)的比例更高,而 NOAC 药物类型或不同的 NOAC 剂量方案在影像学特征或结局方面并无明显差异。结论- 如果抗凝治疗有效,NOAC 相关 ICH 患者与 VKA 相关 ICH 患者的血肿特征和功能结局无差异。临床试验注册- URL:https://www.clinicaltrials.gov. 唯一标识符:NCT03093233.