Second Department of Neurology, Attikon University Hospital, National & Kapodistrian University of Athens, Athens.
Department of Neurology, University of Ioannina, Ioannina, Greece.
Eur J Neurol. 2018 Oct;25(10):1299-1302. doi: 10.1111/ene.13742. Epub 2018 Jul 21.
Intracranial hemorrhage (ICH) is the most feared complication in patients treated with oral anticoagulants due to non-valvular atrial fibrillation. Non-vitamin K oral anticoagulants (NOACs) reduce the risk of ICH compared with vitamin K antagonists (VKAs). We performed a systematic review and meta-analysis to evaluate the risk of fatal NOAC-related ICH compared with VKA-related ICH.
We calculated the corresponding risk ratios (RRs) in each included study to express the relative risk of fatal ICH amongst all patients receiving oral anticoagulation with either NOACs or VKAs. We additionally evaluated the mortality rates in NOAC-related ICH in patients treated with and without NOAC-specific reversal agents (idarucizumab and factor Xa inhibitors antidote). Case fatality was evaluated at 30-90 days following symptom onset.
Our literature search identified six eligible studies (four randomized controlled trials and two open-label trials of NOAC-specific reversal agents). In pairwise analyses, NOACs were found to have a lower risk of fatal ICH compared with VKAs [RR, 0.46; 95% confidence interval (CI), 0.36-0.58] with no heterogeneity (I = 0%) across included randomized controlled trials. However, the case fatality rate was similar in NOAC-related and VKA-related (RR, 1.00; 95% CI, 0.84-1.19) ICH with no evidence of heterogeneity (I = 0%). In the indirect analysis, the case fatality rate of NOAC-related ICH in patients treated with specific reversal agents was lower compared with the remainder of the patients [17% (95% CI, 11-24%) vs. 41% (95% CI, 34-49%); P < 0.001].
Non-vitamin K oral anticoagulants halve the risk of fatal ICH in patients with non-valvular atrial fibrillation compared with VKAs, whereas indirect comparisons indicate that NOAC-specific reversal agents may be associated with a lower case fatality rate in NOAC-related ICH.
颅内出血（ICH）是接受口服抗凝剂治疗的非瓣膜性心房颤动患者最担心的并发症。非维生素 K 口服抗凝剂（NOACs）与维生素 K 拮抗剂（VKAs）相比，降低了 ICH 的风险。我们进行了一项系统评价和荟萃分析，以评估与 VKA 相关的 ICH 相比，致命性 NOAC 相关 ICH 的风险。
我们计算了每个纳入研究中的相应风险比（RR），以表示接受 NOAC 或 VKAs 抗凝治疗的所有患者中致命性 ICH 的相对风险。我们还评估了在接受和未接受 NOAC 特异性逆转剂（依达鲁珠单抗和因子 Xa 抑制剂解毒剂）治疗的患者中，NOAC 相关 ICH 的死亡率。病例死亡率在症状发作后 30-90 天进行评估。
我们的文献检索确定了六项合格的研究（四项随机对照试验和两项 NOAC 特异性逆转剂的开放标签试验）。在成对分析中，与 VKAs 相比，NOACs 发生致命性 ICH 的风险较低[RR，0.46；95%置信区间（CI），0.36-0.58]，纳入的随机对照试验无异质性（I = 0%）。然而，NOAC 相关和 VKA 相关（RR，1.00；95%CI，0.84-1.19）ICH 的病例死亡率相似，无异质性证据（I = 0%）。在间接分析中，接受特异性逆转剂治疗的患者中，NOAC 相关 ICH 的病死率低于其余患者[17%（95%CI，11-24%）比 41%（95%CI，34-49%）；P < 0.001]。
与 VKAs 相比，非维生素 K 口服抗凝剂可将非瓣膜性心房颤动患者致命性 ICH 的风险降低一半，而间接比较表明，NOAC 特异性逆转剂可能与 NOAC 相关 ICH 的病死率降低相关。
