The Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
Department of Neurology, Duke University Medical Center, Durham, North Carolina.
JAMA Netw Open. 2021 Feb 1;4(2):e2037438. doi: 10.1001/jamanetworkopen.2020.37438.
Although the use of factor Xa (FXa) inhibitors has increased substantially over the past decade, there are limited data on characteristics and outcomes of FXa inhibitor-associated intracerebral hemorrhage (ICH).
To investigate the association between prior oral anticoagulant use (FXa inhibitors, warfarin, or none) and in-hospital outcomes among patients with nontraumatic ICH.
DESIGN, SETTING, AND PARTICIPANTS: This is a cohort study of 219 701 patients with nontraumatic ICH admitted to 1870 hospitals in the Get With The Guidelines-Stroke registry between October 2013 and May 2018. Data analysis was performed in December 2019.
Anticoagulation therapy before ICH.
The primary outcome was in-hospital mortality. Secondary outcomes were a composite measure of in-hospital mortality or discharge to hospice, discharge home, independent ambulation, and modified Rankin Scale (mRS) score at discharge.
Of 219 701 patients (mean [SD] age, 68.2 [15.3] years; 104 940 women [47.8%]), 9202 (4.2%) were taking FXa inhibitors, 21 430 (9.8%) were taking warfarin, and 189 069 (86.0%) were not taking any oral anticoagulant before ICH. Patients taking FXa inhibitors or warfarin were older and had higher prevalence of cardiovascular risk factors. Compared with those not taking an oral anticoagulant (42 660 of 189 069 patients [22.6%]), the in-hospital mortality risk was higher for both FXa inhibitors (2487 of 9202 patients [27.0%]; adjusted odds ratio [aOR], 1.27; 95% CI, 1.20-1.34; P < .001) and warfarin (7032 of 21 430 patients [32.8%]; aOR, 1.67; 95% CI, 1.60-1.74; P < .001). Both FXa inhibitors (3478 of 9202 patients [37.8%]; aOR, 1.19; 95% CI, 1.13-1.26; P < .001) and warfarin (9151 of 21 430 patients [42.7%]; aOR, 1.50; 95% CI, 1.44-1.56; P < .001) were associated with higher odds of death or discharge to hospice compared with not taking oral anticoagulation (58 022 of 189 069 patients [30.7%]). Although the rates of discharge home, independent ambulation, mRS scores of 0 or 1, and mRS scores of 0 to 2 were numerically lower among patients taking FXa inhibitors, these differences were not significant compared with patients not taking oral anticoagulants. In contrast, patients taking FXa inhibitors were less likely to die (aOR, 0.76; 95% CI, 0.72-0.81; P < .001) or to experience death or discharge to hospice (aOR, 0.79; 95% CI, 0.75-0.84; P < .001), more likely to be discharged home (aOR, 1.18; 95% CI, 1.10-1.26; P < .001), and had better mRS scores at discharge (eg, mRS scores of 0-1: aOR, 1.24; 95% CI, 1.09-1.40; P < .001) than those treated with warfarin. Concomitant warfarin and antiplatelet therapy (either single or dual) was associated with worse outcomes compared with taking warfarin alone (eg, in-hospital mortality for dual-antiplatelet agents: aOR, 2.07; 95% CI, 1.72-2.50; P < .001). However, such incremental risk was not significant in patients taking FXa inhibitors.
In this cohort study, FXa inhibitor-associated ICH was associated with higher risk of mortality or death or discharge to hospice than not taking an oral anticoagulant, but patients taking FXa inhibitors had better outcomes than those with warfarin-related ICH.
尽管在过去十年中,因子 Xa(FXa)抑制剂的使用大幅增加,但关于 FXa 抑制剂相关的颅内出血(ICH)的特征和结局的数据有限。
调查非创伤性 ICH 患者中先前使用口服抗凝剂(FXa 抑制剂、华法林或无抗凝剂)与住院期间结局之间的关联。
设计、地点和参与者:这是一项队列研究,纳入了 2013 年 10 月至 2018 年 5 月在 Get With The Guidelines-Stroke 登记处的 1870 家医院中 219701 例非创伤性 ICH 患者。数据分析于 2019 年 12 月进行。
ICH 发生前的抗凝治疗。
主要结局是住院期间死亡率。次要结局是住院期间死亡率或死亡或出院至临终关怀、出院回家、独立行走和出院时改良 Rankin 量表(mRS)评分的复合测量指标。
在 219701 例患者(平均[标准差]年龄,68.2[15.3]岁;女性 104940 例[47.8%])中,9202 例(4.2%)服用 FXa 抑制剂,21430 例(9.8%)服用华法林,189069 例(86.0%)在 ICH 发生前未服用任何口服抗凝剂。服用 FXa 抑制剂或华法林的患者年龄较大,且心血管危险因素的患病率更高。与未服用口服抗凝剂的患者(189069 例中的 42660 例[22.6%])相比,服用 FXa 抑制剂(9202 例中的 2487 例[27.0%];调整后的优势比[OR],1.27;95%CI,1.20-1.34;P<0.001)和华法林(21430 例中的 7032 例[32.8%];OR,1.67;95%CI,1.60-1.74;P<0.001)的住院期间死亡率风险更高。服用 FXa 抑制剂(9202 例中的 3478 例[37.8%];OR,1.19;95%CI,1.13-1.26;P<0.001)和华法林(21430 例中的 9151 例[42.7%];OR,1.50;95%CI,1.44-1.56;P<0.001)与未服用口服抗凝剂相比,死亡或死亡或出院至临终关怀的可能性更高(189069 例中的 58022 例[30.7%])。虽然与未服用口服抗凝剂的患者相比,服用 FXa 抑制剂的患者出院回家、独立行走、mRS 评分 0 或 1 以及 mRS 评分 0 至 2 的比例较低,但与未服用口服抗凝剂的患者相比,这些差异无统计学意义。相比之下,服用 FXa 抑制剂的患者死亡(OR,0.76;95%CI,0.72-0.81;P<0.001)或经历死亡或死亡或出院至临终关怀(OR,0.79;95%CI,0.75-0.84;P<0.001)的可能性更低,出院回家(OR,1.18;95%CI,1.10-1.26;P<0.001)的可能性更高,出院时的 mRS 评分更好(例如,mRS 评分 0-1:OR,1.24;95%CI,1.09-1.40;P<0.001),而服用华法林的患者则更低。与单独服用华法林相比,同时服用华法林和抗血小板药物(单一或双重)与更差的结局相关(例如,双重抗血小板药物的住院期间死亡率:OR,2.07;95%CI,1.72-2.50;P<0.001)。然而,在服用 FXa 抑制剂的患者中,这种增量风险并不显著。
在这项队列研究中,与未服用口服抗凝剂相比,服用 FXa 抑制剂相关的 ICH 与更高的死亡率或死亡或死亡或出院至临终关怀风险相关,但服用 FXa 抑制剂的患者的结局优于华法林相关 ICH 的患者。