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Circulation:炎症是否会影响evolocumab降低LDL-C和心血管意外风险的效果?

2018-07-10 MedSci MedSci原创

FOURIER试验发现PCSK9(9型前体蛋白转化酶枯草杆菌蛋白酶/kexin)抑制剂evolocumab可降低低密度脂蛋白(LDL-C)和心血管意外风险。但是,evolocumab的疗效是否受基础炎症风险影响,尚未明确。Erin A. Bohula等人以基线高敏的C反应蛋白(hsCRP)将FOURIER试验的受试者分层来研究evolocumab的疗效。本试验共纳入27564位采用一种他汀类药物治

FOURIER试验发现PCSK9(9型前体蛋白转化酶枯草杆菌蛋白酶/kexin)抑制剂evolocumab可降低低密度脂蛋白(LDL-C)和心血管意外风险。但是,evolocumab的疗效是否受基础炎症风险影响,尚未明确。Erin A. Bohula等人以基线高敏的C反应蛋白(hsCRP)将FOURIER试验的受试者分层来研究evolocumab的疗效。

本试验共纳入27564位采用一种他汀类药物治疗、LDL-C维持在70mg/dL以上的稳定型动脉粥样硬化性心血管疾病患者,将其随机分至evolocumab或安慰剂组。中位随访2.2年(1.8-2.5)。主要评估指标是心血管因素死亡、心肌梗死卒中、因不稳定型心绞痛或冠脉重建住院,心血管因素死亡、心肌梗死或卒中的关键次要结点是对比基线hsCRP的分层(<1、1-3和>3mg/dL)。此外,还以基线hsCRP和1个月时的LDL-C评估预后。

基线hsCRP<1、1-3和>3mg/dL的患者人数分别是7981位(29%)、11177位(41%)和8337位(30%)。基线hsCRP中位值是1.8(0.9-3.6)mg/L,其水平不随着evolocumab用药改变(48周时两组hsCRP的变化水平均为-0.2mg/dL[-1.0~0.4])。安慰剂组,基线hsCRP较高的患者的主要和次要结点关键点的3年Kaplan-Meier率显著更高:基线hsCRP<1、1-3和>3mg/dL的三组患者的主要结点的3年Kaplan-Meier率分别是12.0%、13.7%和18.1%(p<0.0001),次要结点关键点的分别是7.4%、9.1%和13.2%(p<0.0001)。对于不同的hsCRP分层,evolocumab降低主要结点和次要结点关键点的相对风险的作用相同。而与此相反,高hsCRP的患者应用evolocumab时绝对风险降低最明显:主要结点各层分别是1.6%、1.8%和2.6%,次要结点各层分别是0.8%、2.0%和3.0%。对LDL-C/hsCRP与心血管风险之间的关联进行校正分析显示LDL-C和hsCRP均与主要结点独立相关(p<0.0001)。

用evolocumab降低LDL-C水平可减少各个hsCRP分层的心血管事件,基线hsCRP越高,绝对风险降低越明显。hsCRP和LDL-C水平越低,患者发生心血管意外的风险就越低。

原始出处:

Erin A. Bohula, et al. Inflammatory and Cholesterol Risk in the FOURIER Trial. Circulation:July 10,2018.https://doi.org/10.1161/CIRCULATIONAHA.118.034032

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    2018-08-21 snf701207
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    2018-07-12 zhwj
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    2018-07-11 1209e435m98(暂无昵称)

    学习了.谢谢分享

    0

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    2018-07-10 CHANGE

    疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1912006, encodeId=e060191200603, content=<a href='/topic/show?id=4de7112046c' target=_blank style='color:#2F92EE;'>#mAb#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11204, encryptionId=4de7112046c, topicName=mAb)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=25e7304, createdName=snf701207, createdTime=Tue Aug 21 02:32:00 CST 2018, time=2018-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1422569, encodeId=b63b1422569f8, content=<a href='/topic/show?id=58b810e5814' target=_blank style='color:#2F92EE;'>#LDL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10758, encryptionId=58b810e5814, topicName=LDL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=382c3719677, createdName=zhwj, createdTime=Thu Jul 12 11:32:00 CST 2018, time=2018-07-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1426479, encodeId=9c0a14264e9ce, content=<a href='/topic/show?id=96fae1243b' target=_blank style='color:#2F92EE;'>#Evolocumab#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7124, encryptionId=96fae1243b, topicName=Evolocumab)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ce534073393, createdName=ZGMFX25A, createdTime=Thu Jul 12 11:32:00 CST 2018, time=2018-07-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=330752, encodeId=8010330e52b0, content=学习了.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=192, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Wed Jul 11 05:55:15 CST 2018, time=2018-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1046565, encodeId=0b85104656590, content=疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的, beContent=null, objectType=article, channel=null, level=null, likeNumber=143, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Tue Jul 10 23:32:00 CST 2018, time=2018-07-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=330671, encodeId=3a393306e190, content=谢谢分享学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=125, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM7GibvIBibibnnnvpajk2stlDF5oichYahI6Bia8uxeTBFoPbdoHWebyXf9eal9FNgUF2lNcrwoZicM3BvQ/0, createdBy=a3742066385, createdName=戒馋,懒,贪, createdTime=Tue Jul 10 20:49:30 CST 2018, time=2018-07-10, status=1, ipAttribution=)]
    2018-07-10 戒馋,懒,贪

    谢谢分享学习了

    0

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