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NEJM:不明来源栓塞性卒中,抗凝还是抗血小板?

2019-06-12 杨中华 脑血管病及重症文献导读

大部分卒中为缺血性梗死,其病因分为:大动脉颅外或颅内动脉粥样硬化、心源性栓塞、小动脉闭塞和其他病因,以及少见病因。然而,20-30%的缺血性卒中为隐源性卒中,如果影像上提示为栓塞性(非腔隙)梗死并且经过一系列检查未找到栓子来源,此时这些隐源性卒中称为不明来源栓塞性卒中(embolic strokes of undetermined source,ESUS)。


大部分卒中为缺血性梗死,其病因分为:大动脉颅外或颅内动脉粥样硬化、心源性栓塞、小动脉闭塞和其他病因,以及少见病因。然而,20-30%的缺血性卒中为隐源性卒中,如果影像上提示为栓塞性(非腔隙)梗死并且经过一系列检查未找到栓子来源,此时这些隐源性卒中称为不明来源栓塞性卒中(embolic strokes of undetermined source,ESUS)。

在卒中二级预防指南中推荐隐源性卒中患者应该给予抗血小板治疗,包括阿司匹林、缓释双嘧达莫联合阿司匹林、或氯吡格雷和阿司匹林。研究显示口服抗凝剂,包括达比加群酯,能够降低高风险心源性因素比如房颤引起的卒中复发。

2019年5月来自德国的H.-C. Diener等在 NEJM 上公布了RE-SPECT ESUS 试验结果,目的在于比较达比加群和阿司匹林预防卒中复发的有效性和安全性。

RE-SPECT ESUS是一项国际、双盲、平行组、随机试验。从2014年12月到2018年1月来自42个国家564家医院参与了该试验。

纳入标准包括年龄>=60岁,前3个月内发生过不明来源栓塞性卒中(ESUS),或前6个月内但是至少合并一项血管危险因素;年龄介于18-59岁,前3个月内发生过卒中,并且至少合并一项额外的血管危险因素。

ESUS 定义为:非腔隙性缺血性卒中(脑影像学检测),卒中供血动脉区域无颅外或颅内动脉粥样硬化>=50%狭窄(动脉影像学或颈部和经颅多普勒超声),>=20h 心律监测未发现时间持续超过6min 的房颤,经胸或经食道未检测到心脏内栓子,以及无其他卒中的特殊病因。

纳入的患者按照1:1的比例随机(双盲)给予达比加群和阿司匹林安慰剂或阿司匹林和达比加群安慰剂。达比加群的剂量为150mg 每天两次,年龄>=70岁估计肌酐清除率介于30-50 ml/min 者,达比加群剂量为110 mg 每天两次。在阿司匹林组,给予了nonenteric-coated 阿司匹林,剂量为100mg,每天一次。对于达比加群组合并冠心病的患者,患者能够接受阿司匹林治疗;在阿司匹林组,合并冠心病者给予阿司匹林加安慰剂。试验期限计划最小为6个月,最大为3.5年。

主要终点为卒中复发,主要安全性终点为严重出血。

该研究共纳入了5390例患者,其中达比加群组2695例,阿司匹林组2695例。在随访19个月期间,达比加群组和阿司匹林组卒中复发率分别为6.6%(每年4.1%)和7.7%(每年4.8%)(HR, 0.85; 95% CI, 0.69 to 1.03; P = 0.10)。达比加群组和阿司匹林组缺血性卒中发生率分别为4.0%/年和4.7%/年(HR, 0.84; 95% CI, 0.68 to 1.03)。严重出血分别为1.7%/年和1.4%/年(HR, 1.19; 95% CI, 0.85 to 1.66)。临床相关非严重出血发生率分别为1.6%/年和0.9%/年。

最终作者认为对于近期 ESUS 的患者,在预防卒中复发方面达比加群并不优于阿司匹林。达比加群组大出血的发生率未明显高于阿司匹林组,但是达比加群组临床相关非严重出血更常见。

重要数据:

1.基线数据:达比加群和阿司匹林组年龄分别为,64.5和63.9岁;卒中到随机的时间,46和43天;平均 NIHSS 1和1分;既往卒中和 TIA,17.6%和18.6%;PFO,11.8%和13.4%。

2.预后数据:残疾性卒中0.6%和0.9%(HR 0.59;95% CI 0.36–0.96);VTE,0.5%和0.4%(HR 0.59;95% CI 0.26–1.34);严重或临床相关非严重出血,3.3%和2.3%(HR 1.44;95% CI 1.12–1.85)。

3.亚组数据:以下亚组有可能获益,但是需要进一步证实,包括年龄>=75岁,亚洲人,达比加群110mg,使用质子泵,卒中到随机的时间31天以上,既往卒中或 TIA,基线时心脏监测持续时间<=48h,CHA2DS2–VASc>=5,无 PFO。

4.>=20h ECG监测,外加院外延长时间 ECG 监测的患者比例为14%。随机后发现房颤(在延长监测期间房颤持续时间超过6min)的比例分别为0.9%和0.7%。

5.本试验和NAVIGATE ESUS试验设计上的差异:后者采用了低剂量利伐沙班,前者只有年龄>=75岁且肾功能受损者才给予低剂量达比加群(110mg bid)。后者随访11个月,前者为19个月。后者阿司匹林组出血的几率低于前者的阿司匹林组。后者阿司匹林剂型为enteric-coated form,前者为 plain form。

原始出处:

N Engl J Med. 2019 May 16;380(20):1906-1917. doi: 10.1056/NEJMoa1813959.

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    2019-06-15 yjs木玉

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    2019-06-13 健健

    卒中虽然是临床上常见病,溶栓,取栓等血管内治疗也很成熟,但是仍然有很多未知问题有待认知!

    0

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    2019-06-13 旺医

    顶刊就是顶刊,谢谢梅斯带来这么高水平的研究报道,我们科里同事经常看梅斯,分享梅斯上的信息

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=367763, encodeId=b11636e763d1, content=好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=106, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Sat Jun 15 06:29:29 CST 2019, time=2019-06-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1536281, encodeId=ffc1153628109, content=<a href='/topic/show?id=87ec6201043' target=_blank style='color:#2F92EE;'>#栓塞性卒中#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=62010, encryptionId=87ec6201043, topicName=栓塞性卒中)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6a5012676127, createdName=jiekemin, createdTime=Fri Jun 14 14:14:00 CST 2019, time=2019-06-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1026386, encodeId=f5e3102638665, content=卒中虽然是临床上常见病,溶栓,取栓等血管内治疗也很成熟,但是仍然有很多未知问题有待认知!, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=健健, createdTime=Thu Jun 13 02:14:00 CST 2019, time=2019-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1034849, encodeId=27df1034849b5, content=顶刊就是顶刊,谢谢梅斯带来这么高水平的研究报道,我们科里同事经常看梅斯,分享梅斯上的信息, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=旺医, createdTime=Thu Jun 13 02:14:00 CST 2019, time=2019-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=367665, encodeId=c1aa36e665e9, content=学习了很有用不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Thu Jun 13 00:27:16 CST 2019, time=2019-06-13, status=1, ipAttribution=)]
    2019-06-13 飛歌

    学习了很有用不错

    0

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