中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (5): 1005-1006.doi: 10.4103/1673-5374.324837

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

不明原因栓塞性卒中:口服抗凝治疗患者亚组的识别

  

  • 出版日期:2022-05-15 发布日期:2021-11-08

Embolic stroke of undetermined source: identification of patient subgroups for oral anticoagulation treatment

Isabell Greeve, Wolf-Rüdiger Schäbitz*   

  1. Department of Neurology, Evangelisches Klinikum Bethel, University of Bielefeld, Campus Bethel, Bielefeld, Germany
  • Online:2022-05-15 Published:2021-11-08
  • Contact: Wolf-Rüdiger Schäbitz, MD, wolf.schaebitz@evkb.de.

摘要: Neural Regen Res:老年和肾功能不全患者的不明原因栓塞性卒中
目前的证据显然不支持不明原因栓塞性卒中患者从使用达比加群或利伐沙班的抗凝治疗中获益的假设,因此应该像大多数其他隐源性卒中患者一样使用阿司匹林进行治疗。然而,最新试验的亚组分析表明,年龄较大和肾功能受损的患者以及因此设计的接受较低剂量达比加群的患者倾向于从抗凝治疗中获益。基线时肌酐清除率在 30 - < 50 mL/min 之间的阿司匹林治疗达比加群治疗患者中复发性卒中发生率分别为 16.4%和 10.2%。在基线时肌酐清除率介于 50 - < 80 mL/min 之间的患者组中,患者在接受阿司匹林治疗时和达比加群组的复发性卒中发生率分别为8.3%和5.7%。这些发现在很大程度上得到了使用利伐沙班代替达比加群进行口服抗凝治疗的试验数据的证实。另外一个最新试验中年龄大于 75 岁的患者亚组显示阿司匹林和达比加群治疗之间存在显著差异:12.4% 接受阿司匹林治疗的患者发生复发性卒中,而接受达比加群治疗的患者仅为 7.8%。在年龄 > 75 岁且肌酐清除率    < 50 mL/min 的综合危险因素患者中,使用较低剂量的达比加群(110 mg,每天2次)治疗仅导致7.4%的患者复发性卒中,而使用阿司匹林治疗导致13%的患者脑卒中复发。
来自德国比勒费尔德大学的Wolf-Rüdiger Schäbitz团队认为,不明原因栓塞性卒中患者的诊断检查不应仅仅关注心律监测来检测房颤,还必须包括颅外或颅内血管成像以证明明显狭窄 (> 50%)、经胸和/或经食道超声心动图以揭示心源性栓塞来源和调查有血栓栓塞事件风险的遗传性或获得性凝血病。如果主要检查结果仍为阴性,则可以根据当前定义进行不明原因栓塞性卒中诊断。研究人员不应接受该诊断为最终诊断,而应考虑启动更全面的附加诊断,包括三维经食道超声心动图、颅内血管成像(包括斑块测量)、通过植入式环路记录器进行的长期有创心脏监测,甚至心脏磁共振成像。完成后,必须重新定义病因,并且不明原因栓塞性卒中诊断可能被特定病因取代,然后进行治疗调整。不明原因栓塞性卒中患者可能受益于口服抗凝剂的假设已被拒绝,但越来越多的证据表明,在预先指定的亚组中,口服抗凝剂可能具有预防复发性栓塞性卒中的潜力。专门的诊断检查至关重要,不仅可以剖析正确的病因,还可以防止老年和肾功能不全患者因治疗导致危及生命的出血或严重颅内出血而受到伤害。
    文章在《中国神经再生研究(英文版)》杂志2022年 5月5期发表。

Abstract: Background: Embolic stroke of undetermined source (ESUS), a subtype of cryptogenic stroke, was defined as acute ischemic stroke displaying an embolic or non-lacunar brain infarct pattern on imaging without significant extra or intracranial ipsilateral vessel stenosis or without an identifiable cardioembolic source such as atrial fibrillation (AF) or left ventricular thrombi (Hart et al., 2014). ESUS patients tend to be younger than other stroke patients and have a lower incidence of traditional risk factors such as hypertension, diabetes and hypercholesterolemia, that are key contributors for the development of atherosclerosis, the substrate for small and large vessel disease. Two large clinical trials of embolic stroke of unknown source comparing the direct acting oral anticoagulants rivaroxaban and dabigatran to antiplatelet therapy for secondary stroke prevention, the New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial versus aspirin to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) (Hart et al., 2018) and Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate versus Acetylsalicylic Acid in Patients with Embolic Stroke of Undetermined Source (RESPECT-ESUS) (Diener et al., 2019), showed not only no benefit for ESUS patients treated with oral anticoagulation to prevent recurrent strokes, but showed even higher risk of bleeding while treated with rivaroxaban. Consequently, the study hypothesis of prevention of recurrent stroke by oral anticoagulation with dabigatran and rivaroxaban in patients diagnosed with ESUS had to be rejected, keeping aspirin as primary secondary prevention treatment for this stroke subtype. Although the reasons for the negative study results are probably multifactorial, posthoc analysis and recent cardiac monitoring studies in ESUS patients suggested that AF may not account for the majority of stroke events in ESUS patients (for example see expert review on ESUS concept, etiology and diagnostic: Schäbitz et al., 2020). In addition to aspects of diagnosis and etiology of ESUS, this topical review will discuss recent evidence from prespecified subgroups of the NAVIGATE- and RESPECT-ESUS trials suggesting a benefit for patients treated with oral anticoagulation with regard to secondary stroke prevention.