Inohara Taku, Xian Ying, Liang Li, Matsouaka Roland A, Saver Jeffrey L, Smith Eric E, Schwamm Lee H, Reeves Mathew J, Hernandez Adrian F, Bhatt Deepak L, Peterson Eric D, Fonarow Gregg C
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
Department of Neurology, Duke University Medical Center, Durham, North Carolina.
JAMA. 2018 Feb 6;319(5):463-473. doi: 10.1001/jama.2017.21917.
Although non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used to prevent thromboembolic disease, there are limited data on NOAC-related intracerebral hemorrhage (ICH).
To assess the association between preceding oral anticoagulant use (warfarin, NOACs, and no oral anticoagulants [OACs]) and in-hospital mortality among patients with ICH.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 141 311 patients with ICH admitted from October 2013 to December 2016 to 1662 Get With The Guidelines-Stroke hospitals.
Anticoagulation therapy before ICH, defined as any use of OACs within 7 days prior to hospital arrival.
In-hospital mortality.
Among 141 311 patients with ICH (mean [SD] age, 68.3 [15.3] years; 48.1% women), 15 036 (10.6%) were taking warfarin and 4918 (3.5%) were taking NOACs preceding ICH, and 39 585 (28.0%) and 5783 (4.1%) were taking concomitant single and dual antiplatelet agents, respectively. Patients with prior use of warfarin or NOACs were older and had higher prevalence of atrial fibrillation and prior stroke. Acute ICH stroke severity (measured by the National Institutes of Health Stroke Scale) was not significantly different across the 3 groups (median, 9 [interquartile range, 2-21] for warfarin, 8 [2-20] for NOACs, and 8 [2-19] for no OACs). The unadjusted in-hospital mortality rates were 32.6% for warfarin, 26.5% for NOACs, and 22.5% for no OACs. Compared with patients without prior use of OACs, the risk of in-hospital mortality was higher among patients with prior use of warfarin (adjusted risk difference [ARD], 9.0% [97.5% CI, 7.9% to 10.1%]; adjusted odds ratio [AOR], 1.62 [97.5% CI, 1.53 to 1.71]) and higher among patients with prior use of NOACs (ARD, 3.3% [97.5% CI, 1.7% to 4.8%]; AOR, 1.21 [97.5% CI, 1.11-1.32]). Compared with patients with prior use of warfarin, patients with prior use of NOACs had a lower risk of in-hospital mortality (ARD, -5.7% [97.5% CI, -7.3% to -4.2%]; AOR, 0.75 [97.5% CI, 0.69 to 0.81]). The difference in mortality between NOAC-treated patients and warfarin-treated patients was numerically greater among patients with prior use of dual antiplatelet agents (32.7% vs 47.1%; ARD, -15.0% [95.5% CI, -26.3% to -3.8%]; AOR, 0.50 [97.5% CI, 0.29 to 0.86]) than among those taking these agents without prior antiplatelet therapy (26.4% vs 31.7%; ARD, -5.0% [97.5% CI, -6.8% to -3.2%]; AOR, 0.77 [97.5% CI, 0.70 to 0.85]), although the interaction P value (.07) was not statistically significant.
Among patients with ICH, prior use of NOACs or warfarin was associated with higher in-hospital mortality compared with no OACs. Prior use of NOACs, compared with prior use of warfarin, was associated with lower risk of in-hospital mortality.
尽管非维生素K拮抗剂口服抗凝剂(NOACs)越来越多地用于预防血栓栓塞性疾病,但关于NOAC相关的脑出血(ICH)的数据有限。
评估ICH患者先前使用口服抗凝剂(华法林、NOACs和未使用口服抗凝剂[OACs])与住院死亡率之间的关联。
设计、设置和参与者:对2013年10月至2016年12月期间入住1662家“遵循指南-卒中”医院的141311例ICH患者进行回顾性队列研究。
ICH前的抗凝治疗,定义为入院前7天内任何OACs的使用。
住院死亡率。
在141311例ICH患者中(平均[标准差]年龄,68.3[15.3]岁;48.1%为女性),15036例(10.6%)在ICH前服用华法林,4918例(3.5%)在ICH前服用NOACs,39585例(28.0%)和5783例(4.1%)分别同时服用单一和双重抗血小板药物。先前使用华法林或NOACs的患者年龄较大,房颤和既往卒中的患病率较高。3组间急性ICH卒中严重程度(通过美国国立卫生研究院卒中量表测量)无显著差异(华法林组中位数为9[四分位间距,2-21],NOACs组为8[2-20],未使用OACs组为8[2-19])。未调整的住院死亡率在华法林组为32.6%,NOACs组为26.5%,未使用OACs组为22.5%。与未先前使用OACs的患者相比,先前使用华法林的患者住院死亡风险更高(调整风险差异[ARD],9.0%[97.5%CI,7.9%至10.1%];调整比值比[AOR],1.62[97.5%CI,1.53至1.71]),先前使用NOACs的患者住院死亡风险也更高(ARD,3.3%[97.5%CI,1.7%至4.8%];AOR,1.21[97.5%CI,1.11-1.32])。与先前使用华法林的患者相比,先前使用NOACs的患者住院死亡风险较低(ARD,-5.7%[97.5%CI,-7.3%至-4.2%];AOR,0.75[97.5%CI,0.69至0.81])。在先前使用双重抗血小板药物的患者中,NOAC治疗患者与华法林治疗患者之间的死亡率差异在数值上更大(32.7%对47.1%;ARD,-15.0%[95.5%CI,-26.3%至-3.8%];AOR,0.50[97.5%CI,0.29至0.86]),高于未先前接受抗血小板治疗而服用这些药物的患者(26.4%对31.7%;ARD,-5.0%[97.5%CI,-6.8%至-3.2%];AOR,0.77[97.5%CI,0.70至0.85]),尽管交互作用P值(.07)无统计学意义。
在ICH患者中,与未使用OACs相比,先前使用NOACs或华法林与更高的住院死亡率相关。与先前使用华法林相比,先前使用NOACs与较低的住院死亡风险相关。