Lancet:默克公司潜在重磅炸弹治疗高胆固醇血症

2015-03-04 赵洲译 MedSci原创

家族性高胆固醇血症是一种显性常染色体疾病。其标志就是血浆中低密度脂蛋白胆固醇(LDL-C)浓度偏高。高胆固醇血症是由于基因突变引起的。编码LDL受体,载脂蛋白B(APOB)或原蛋白的基因发生突变。如果不进行治疗,患者死于原发性心血管疾病相关的疾病风险将会增加。抑制胆固醇酯转移蛋白已经表明了可以降低LDL-C浓度。Anacetrapib是有效的胆固醇酯转移蛋白抑制剂。默克公司对其进行了三期临床试验(

家族性高胆固醇血症是一种显性常染色体疾病。其标志就是血浆中低密度脂蛋白胆固醇(LDL-C)浓度偏高。高胆固醇血症是由于基因突变引起的。编码LDL受体,载脂蛋白BAPOB)或原蛋白的基因发生突变。如果不进行治疗,患者死于原发性心血管疾病相关的疾病风险将会增加。抑制胆固醇酯转移蛋白已经表明了可以降低LDL-C浓度。Anacetrapib是有效的胆固醇酯转移蛋白抑制剂。默克公司对其进行了三期临床试验(随机、双盲、安慰剂对照试验)。

试验中共有306人参与。其中204人服用anacetrapib100mg,每天一次),102人作为安慰剂对照组。Anacetrapib组共有174人成功完成了为期52周的治疗过程,对照组有88人完成试验。试验参与者年龄在18-80岁之间,通过基因型鉴定或临床诊断为家族性高胆固醇血症。参与者经过至少六周的最适条件降脂治疗,LDL-C浓度为2.59mmol/L或更高且无心血管疾病或者浓度为1.81mmol/L或更高且有心血管疾病。研究人员对参与者服药期间及治疗结束后12周进行跟踪随访。主要监测指标就是LDL-C浓度相对于基线的变化。

2012年到2014年两年的试验中,给药组使LDL-C平均浓度从3.3mmol/L降低到2.1mmol/L,降低了36%。而安慰剂组平均LDL-C浓度则出现了上升,从3.4mmol/L上升到3.5mmol/L,上升了3.7%。相对于安慰剂组,给药组心血管疾病数量增多。

本次试验中,使用anacetrapib治疗家族性高胆固醇血症患者有着良好的顺应性并且LDL-C浓度出现了实质性地降低。这一改变是否导致心血管疾病减少发生仍然需要进一步试验证明。

原始出处:

John J P Kastelein et al.Anacetrapib as lipid-modifying therapy in patients with heterozygous familial hypercholesterolaemia (REALIZE):a randomised, double-blind, placebo-controlled, phase 3 study.The Lancet.Published online: March 2, 2015

 

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    2015-04-13 howi
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  5. [GetPortalCommentsPageByObjectIdResponse(id=2075671, encodeId=578120e567118, content=<a href='/topic/show?id=c69f9600543' target=_blank style='color:#2F92EE;'>#重磅炸弹#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96005, encryptionId=c69f9600543, topicName=重磅炸弹)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ed25376, createdName=gdsun, createdTime=Mon Apr 27 02:35:00 CST 2015, time=2015-04-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1828022, encodeId=531c182802296, content=<a href='/topic/show?id=1b6210686b2' target=_blank style='color:#2F92EE;'>#Lancet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10686, encryptionId=1b6210686b2, topicName=Lancet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3f0227, createdName=howi, createdTime=Mon Apr 13 02:35:00 CST 2015, time=2015-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1822546, encodeId=104f182254654, content=<a href='/topic/show?id=41311033568e' target=_blank style='color:#2F92EE;'>#默克公司#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103356, encryptionId=41311033568e, topicName=默克公司)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=669d219, createdName=mgqwxj, createdTime=Fri Nov 20 00:35:00 CST 2015, time=2015-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273877, encodeId=f17b12e387781, content=<a href='/topic/show?id=4909103353c5' target=_blank style='color:#2F92EE;'>#默克#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103353, encryptionId=4909103353c5, topicName=默克)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2ba9118, createdName=makuansheng, createdTime=Fri Mar 06 05:35:00 CST 2015, time=2015-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1380014, encodeId=9159138001423, content=<a href='/topic/show?id=bef6102602a9' target=_blank style='color:#2F92EE;'>#高胆固醇血症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102602, encryptionId=bef6102602a9, topicName=高胆固醇血症)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1d1470, createdName=刘阔, createdTime=Fri Mar 06 05:35:00 CST 2015, time=2015-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1548789, encodeId=c5261548e89f4, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Fri Mar 06 05:35:00 CST 2015, time=2015-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=17592, encodeId=dade1e5922c, content=这个效果显著啊, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=drhqh240, createdTime=Wed Mar 04 17:06:00 CST 2015, time=2015-03-04, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=2075671, encodeId=578120e567118, content=<a href='/topic/show?id=c69f9600543' target=_blank style='color:#2F92EE;'>#重磅炸弹#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96005, encryptionId=c69f9600543, topicName=重磅炸弹)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ed25376, createdName=gdsun, createdTime=Mon Apr 27 02:35:00 CST 2015, time=2015-04-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1828022, encodeId=531c182802296, content=<a href='/topic/show?id=1b6210686b2' target=_blank style='color:#2F92EE;'>#Lancet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10686, encryptionId=1b6210686b2, topicName=Lancet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3f0227, createdName=howi, createdTime=Mon Apr 13 02:35:00 CST 2015, time=2015-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1822546, encodeId=104f182254654, content=<a href='/topic/show?id=41311033568e' target=_blank style='color:#2F92EE;'>#默克公司#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103356, encryptionId=41311033568e, topicName=默克公司)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=669d219, createdName=mgqwxj, createdTime=Fri Nov 20 00:35:00 CST 2015, time=2015-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273877, encodeId=f17b12e387781, content=<a href='/topic/show?id=4909103353c5' target=_blank style='color:#2F92EE;'>#默克#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103353, encryptionId=4909103353c5, topicName=默克)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2ba9118, createdName=makuansheng, createdTime=Fri Mar 06 05:35:00 CST 2015, time=2015-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1380014, encodeId=9159138001423, content=<a href='/topic/show?id=bef6102602a9' target=_blank style='color:#2F92EE;'>#高胆固醇血症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102602, encryptionId=bef6102602a9, topicName=高胆固醇血症)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1d1470, createdName=刘阔, createdTime=Fri Mar 06 05:35:00 CST 2015, time=2015-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1548789, encodeId=c5261548e89f4, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Fri Mar 06 05:35:00 CST 2015, time=2015-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=17592, encodeId=dade1e5922c, content=这个效果显著啊, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=drhqh240, createdTime=Wed Mar 04 17:06:00 CST 2015, time=2015-03-04, status=1, ipAttribution=)]
    2015-03-06 xxxx1054
  7. [GetPortalCommentsPageByObjectIdResponse(id=2075671, encodeId=578120e567118, content=<a href='/topic/show?id=c69f9600543' target=_blank style='color:#2F92EE;'>#重磅炸弹#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96005, encryptionId=c69f9600543, topicName=重磅炸弹)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ed25376, createdName=gdsun, createdTime=Mon Apr 27 02:35:00 CST 2015, time=2015-04-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1828022, encodeId=531c182802296, content=<a href='/topic/show?id=1b6210686b2' target=_blank style='color:#2F92EE;'>#Lancet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10686, encryptionId=1b6210686b2, topicName=Lancet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3f0227, createdName=howi, createdTime=Mon Apr 13 02:35:00 CST 2015, time=2015-04-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1822546, encodeId=104f182254654, content=<a href='/topic/show?id=41311033568e' target=_blank style='color:#2F92EE;'>#默克公司#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103356, encryptionId=41311033568e, topicName=默克公司)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=669d219, createdName=mgqwxj, createdTime=Fri Nov 20 00:35:00 CST 2015, time=2015-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273877, encodeId=f17b12e387781, content=<a href='/topic/show?id=4909103353c5' target=_blank style='color:#2F92EE;'>#默克#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103353, encryptionId=4909103353c5, topicName=默克)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2ba9118, createdName=makuansheng, createdTime=Fri Mar 06 05:35:00 CST 2015, time=2015-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1380014, encodeId=9159138001423, content=<a href='/topic/show?id=bef6102602a9' target=_blank style='color:#2F92EE;'>#高胆固醇血症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102602, encryptionId=bef6102602a9, topicName=高胆固醇血症)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1d1470, createdName=刘阔, createdTime=Fri Mar 06 05:35:00 CST 2015, time=2015-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1548789, encodeId=c5261548e89f4, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Fri Mar 06 05:35:00 CST 2015, time=2015-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=17592, encodeId=dade1e5922c, content=这个效果显著啊, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=drhqh240, createdTime=Wed Mar 04 17:06:00 CST 2015, time=2015-03-04, status=1, ipAttribution=)]
    2015-03-04 drhqh240

    这个效果显著啊

    0

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