Circulation:Odyssey Outcomes研究全新分析结果:阿利西尤单抗可降低所有类型卒中风险且不增加出血性卒中风险

2019-11-18 国际循环编辑部 国际循环

在AHA 2019大会上,PCSK9抑制剂相关研究结果再度成为心血管领域的热点。今天,J. Wouter Jukema等发布的Odyssey Outcomes研究结果的再次分析,再度更新了我们对动脉粥样硬化性脑血管疾病的认知。分析结果发现:LDL-C(低密度脂蛋白胆固醇)的降低与出血性卒中之间并无明显相关性;PCSK9抑制剂阿利西尤单抗可降低ACS患者所有类型卒中的风险,且不增加出血性卒中风险,该

在AHA 2019大会上,PCSK9抑制剂相关研究结果再度成为心血管领域的热点。今天,J. Wouter Jukema等发布的Odyssey Outcomes研究结果的再次分析,再度更新了我们对动脉粥样硬化性脑血管疾病的认知。分析结果发现:LDL-C(低密度脂蛋白胆固醇)的降低与出血性卒中之间并无明显相关性;PCSK9抑制剂阿利西尤单抗可降低ACS患者所有类型卒中的风险,且不增加出血性卒中风险,该疗效不受既往脑血管病史及基线LDL-C水平的影响。



荷兰莱顿大学医学中心 J. Wouter Jukema

背景

既往多个降脂治疗荟萃分析发现,降低动脉粥样硬化性脂蛋白(包括LDL-C),可降低初发及再发缺血性卒中的风险。因此,国际指南推荐他汀类药物用于高心血管风险或有心血管疾病伴或不伴脑血管病史的患者,预防包括缺血性卒中在内的脑血管事件。但也有研究1-2发现LDL-C水平非常低可能增加出血性卒中的潜在风险。
 
大型Ⅲ期临床研究Odyssey Outcomes3评估了新型降脂药物PCSK9抑制剂阿利西尤单抗对高强度他汀治疗后LDL-C控制不佳的近期ACS患者的心血管终点的影响,其结果显示,阿利西尤单抗可显著降低该类患者包括卒中在内的复合终点事件15%。

方法

J. Wouter Jukema等4对Odyssey Outcomes研究结果进行再次分析,将研究纳入的18 924例近期ACS患者根据基线LDL-C水平(<80 mg/dl、80~100 mg/dl、≥100 mg/dl)和脑血管疾病史(颈动脉内膜切除术、颈动脉支架置入、既往卒中或TIA病史)进行分层,评估阿利西尤单抗治疗组和安慰剂组缺血性或出血性卒中的发生情况。

结果

阿利西尤单抗治疗组中,LDL-C的降低与出血性卒中之间并无明显相关性,以下是治疗后不同LDL-C水平分层相应的出血性卒中发生率:



阿利西尤单抗治疗可降低所有卒中(HR=0.72,95%CI:0.57~0.91,P=0.005)和缺血性卒中(HR=0.73,95%CI:0.57~0.93,P=0.01)风险,且未增加出血性卒中风险(HR=0.83,95%CI:0.42~1.6,P=0.59)。


 
对于是否合并脑血管病史的患者,阿利西尤单抗的作用相似(交互P=0.37);对于基线LDL-C较高的患者,阿利西尤单抗疗效在数值上更大,但线性趋势并不显著(交互P=0.31)。



结论

该分析显示,在中位随访2.8年期间,阿利西尤单抗可降低高强度他汀治疗后LDL-C控制不佳的近期ACS患者卒中风险,不论基线LDL-C水平如何、是否合并既往脑血管病史。同时,阿利西尤单抗治疗组的LDL-C水平与出血性卒中发生率之间无相关性,即阿利西尤单抗降脂治疗并不增加出血性卒中风险。这一结果为新型降脂药物PCSK9抑制剂阿利西尤单抗在ASCVD患者的应用提供了更详细的循证依据,提示阿利西尤单抗对于ACS合并既往脑血管病史患者的再发卒中具有预防作用,且无发生出血性卒中的安全性顾虑。

原始出处:
J. Wouter Jukema, et al. Effect of Alirocumab on Stroke in ODYSSEY OUTCOMES. Circulation. Nov 11, 2019.

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    2019-11-20 longqijun254
  4. [GetPortalCommentsPageByObjectIdResponse(id=1281327, encodeId=5100128132e5b, content=<a href='/topic/show?id=455f36085f0' target=_blank style='color:#2F92EE;'>#卒中风险#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36085, encryptionId=455f36085f0, topicName=卒中风险)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a8f1167, createdName=wmr111, createdTime=Wed Nov 20 12:16:00 CST 2019, time=2019-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1319567, encodeId=6d42131956eab, content=<a href='/topic/show?id=1dc13145ef8' target=_blank style='color:#2F92EE;'>#出血性卒中#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31457, encryptionId=1dc13145ef8, topicName=出血性卒中)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4193478, createdName=wgx306, createdTime=Wed Nov 20 12:16:00 CST 2019, time=2019-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1590808, encodeId=6ce41590808af, content=<a href='/topic/show?id=0c0b115e4cf' target=_blank style='color:#2F92EE;'>#MES#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11574, encryptionId=0c0b115e4cf, topicName=MES)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=874617863969, createdName=longqijun254, createdTime=Wed Nov 20 12:16:00 CST 2019, time=2019-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1026498, encodeId=5412102649892, 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=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=健健, createdTime=Tue Nov 19 00:16:00 CST 2019, time=2019-11-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1045907, encodeId=2498104590eb2, content=中风是俗称,应该称为缺血性卒中吧, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=guging, createdTime=Tue Nov 19 00:16:00 CST 2019, time=2019-11-19, status=1, ipAttribution=)]
    2019-11-19 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

  5. [GetPortalCommentsPageByObjectIdResponse(id=1281327, encodeId=5100128132e5b, content=<a href='/topic/show?id=455f36085f0' target=_blank style='color:#2F92EE;'>#卒中风险#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36085, encryptionId=455f36085f0, topicName=卒中风险)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a8f1167, createdName=wmr111, createdTime=Wed Nov 20 12:16:00 CST 2019, time=2019-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1319567, encodeId=6d42131956eab, content=<a href='/topic/show?id=1dc13145ef8' target=_blank style='color:#2F92EE;'>#出血性卒中#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31457, encryptionId=1dc13145ef8, topicName=出血性卒中)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4193478, createdName=wgx306, createdTime=Wed Nov 20 12:16:00 CST 2019, time=2019-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1590808, encodeId=6ce41590808af, content=<a href='/topic/show?id=0c0b115e4cf' target=_blank style='color:#2F92EE;'>#MES#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11574, encryptionId=0c0b115e4cf, topicName=MES)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=874617863969, createdName=longqijun254, createdTime=Wed Nov 20 12:16:00 CST 2019, time=2019-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1026498, encodeId=5412102649892, 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=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=健健, createdTime=Tue Nov 19 00:16:00 CST 2019, time=2019-11-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1045907, encodeId=2498104590eb2, content=中风是俗称,应该称为缺血性卒中吧, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=guging, createdTime=Tue Nov 19 00:16:00 CST 2019, time=2019-11-19, status=1, ipAttribution=)]
    2019-11-19 guging

    中风是俗称,应该称为缺血性卒中吧

    0

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