依折麦布PPT.ppt

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Klicken Sie,um das Titelformat zu bearbeiten,Klicken Sie,um die Formate des Vorlagentextes zu bearbeiten,Zweite Ebene,Dritte Ebene,Vierte Ebene,Fnfte Ebene,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Slide,*,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,Click 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edit Master text styles,Second level,Third level,Fourth level,Fifth level,依折麦布,LDL-C,与冠心病相对风险呈对数正相关,LDL,冠心病相对风险,(log),1,0,1,3,1,7,2,2,2,9,3,7,40,70,100,130,160,190,LDL-C,每变化,30 mg/dL(0.8 mmol/L),冠心病相对风险亦相应改变,30%,(,相对风险为,1.0,时，,LDL=40 mg/dl),Grundy SM et al.NCEP ATP III,Circulation 2004;110:227-239,1,0,1,8,2,6,3,3,4,1,4,9,(mg/dl),(mmol/l),-9,-47,-9,-20,-14,-23,-8.5,-19,-11,-34,-50,-45,-40,-35,-30,-25,-20,-15,-10,-5,0,%,Levine GN et al.,N Engl J Med.,1995;332:512-521.,*治疗组和对照组的变化净差,(,P,值指事件,).,TC*,CHD,事件*,N=,入选病例数,.,WHO:,安妥明,N=15,745,P,0.05,Oslo:,饮食,/,戒烟,N=1,232,P,=0.02,Upjohn:,降胆宁,N=2,278,P,0.02,LRC-CPPT:,消胆胺,N=3,806,P,0.05,HHS:,吉非罗齐,N=4,081,P,0.02,降胆固醇有效降低冠心病风险,早期降脂一级预防试验,（,1960,1990,）,Levine GN et al.,N Engl J Med.,1995;332:512-521.,N=,入选人数,;ns=,无显著性差异,.,TC*,CHD,事件*,CDP:,烟酸,(n=1,119)N=8,341,P,=ns,CDP:,安妥明,(n=1,103)N=8,341,P,=ns,Stockholm:,安妥明,+,烟酸,N=555,P0.01,POSCH:,回肠旁路术,N=838,P,0.001,%,*治疗组和对照组的变化净差,(,P,值指事件,).,降胆固醇有效降低冠心病风险,早期降脂二级预防试验,（,1960,1990,）,LDL-C,每降低,10 mmol/L,减少每年主要的心血管事件达,1/5,多,LDL-C,每降低,1.0 mmol/L,引起的相对风险,(RR),降低并不依赖于,LDL-C,的基线,The Lancet.Published,Online,November 9,2010 DOI:10.1016/S0140-6736(10)61350-5,2010 CTT荟萃分析再次证实了LDL-C下降对于主要血管事件的影响,降LDL-C治疗目标值,LDL-C降幅与粥样斑块体积改变,阻止斑块进展,需要,LDL-C,水平至少下降,50%,虚线为平均水平,95%CIs,LDL-C,改变,(%),20,15,10,5,0,-5,-10,-15,粥样斑块体积改变,mm,3,-80,-70,-60,-50,-40,-30,-20,-10,0,10,20,Steven E.Nissen et al.,JAMA.2004;291:1071-1080,极高危,高危,中危,低危,心血管危险分层以及,LDL-C,目标,New goals based on 2007 European society of Cardiology guidelines,Eur Heart J 2011:32:1769-1818,新指南对极高危人群界定更为广泛，,LDL-C,治疗目标值更趋积极,2011 ESC/EAS,指南：更加积极的,LDL-C,目标,中国第二次血脂治疗现状调研结果,中国大部分高危,/,极高危患者未能达标,LDL 70mg/dl,n=137,n=118,n=153,n=361,n=1325,n=2094,86%,79%,66%,39%,36%,23%,LDL 100mg/dl,LDL 160mg/dl,LDL 130mg/dl,LDL 100mg/dl,LDL100mg/dl,为达标目标值,#,基线,LDL=30%,为达标目标值,（采用,2004,年,ATP,的危险分层）,Yangfeng Wu et al.The second multi-center survey of dyslipidemia management in China:goal attainment rate and related factors.Chin J Cardio 2007;35(5):420-427,所有患者均采用他汀治疗,最需要治疗的患者却得不到有效的治疗！,*p0.05,*p50,%,VYVA,研究依折麦布联合辛伐他汀,vs,阿托伐他汀的研究,The VYtorin Versus Atorvastatin study,VYVA研究,The VYtorin Versus Atorvastatin study,Ballantyne CM,et al.Am Heart J,2005;149:464-473,216,个中心,入组人数,=1902,依折麦布,/,辛伐他汀,10/10 n=238,阿托伐他汀,80mg n=239,阿托伐他汀,10mg n=238,依折麦布,/,辛伐他汀,10/40 n=238,依折麦布,/,辛伐他汀,10/20 n=238,依折麦布,/,辛伐他汀,10/80 n=237,阿托伐他汀,20mg n=237,阿托伐他汀,40mg n=237,6,周的治疗期,4,周的导入期,研究设计,（多中心，随机，双盲，平行对照）,使用安慰剂和饮食控制后，,按照,NCEP ATPIII,指南,未达到,LDL-C,目标的患者,VYVA研究结果：联合治疗比他汀单药更加轻松达到50%,依折麦布,/,辛伐他汀组和同剂量阿托伐他汀组疗效对照,*p 0.001,全部配对对照组,6,周后,LDL-C,从基线的变化,*,*,*,*,*,Ballantyne CM,et al.Am Heart J,2005;149:464-473,依折麦布,/,辛伐他汀,阿托伐他汀,VYVA研究结果：联合治疗较换用强效他汀明显提高LDL-C达标率,Ballantyne CM,et al.Am Heart J,2005;149:464-473,LDL-C100mg/dL,LDL-C70mg/dL,患者达到目标水平的比例,%,*P0.05,*P0.01,*P0.001,依折麦布,/,辛伐他汀,阿托伐他汀,VYVA研究结果：联合治疗组具有更加优越的安全性,a,依折麦布,/,辛伐他汀,:10/1010/80 mg;,阿托伐他汀,:1080 mg;,b,连续的监测,;,c,肌酐激酶 研究结束,2,周后升高,Adapted from Ballantyne,et al.,Am Heart J.,2005;149(3):464473.,依折麦布/辛伐他汀 vs 瑞舒伐他汀研究,依折麦布/益适纯 vs 瑞舒伐他汀研究,设计,多中心、双盲、随机、平行对照研究,10周研究(4周安慰剂导入期、之后是6周的双盲期),入选标准,LDL-C 范围从145 到250 mg/dL(3.76.5 mmol/L),甘油三酯,350 mg/dL(,4.0 mmol/L),治疗方案,依折麦布,/辛伐他汀 10/20,10/40,or 10/80 mg,瑞舒伐他汀 10,20,or 40 mg,LDL-C=low-density lipoprotein cholesterol.,Adapted from Catapano AL,et al.,Curr Med Res Opin.,2006;22(10):20412053.,Slide,26,依折麦布,/,辛伐他汀起始剂量可显著降,LDL-C,a,P,0.001 vs rosuvastatin.,Adapted from Catapano AL,et al.,Curr Med Res Opin.,2006;22(10):20412053.,第,6,周相对基线的变化（,%,）,0,45,50,55,40,瑞舒伐他汀,10 mg,(n=475),-45.8%,依折麦布,/,辛伐他汀,10/20 mg,(n=476),51.5%,a,60,Slide,27,依折麦布,/,辛伐他汀让高危患者更易达标,a,P,=NS;,b,P,=0.011 vs rosuvastatin 10 to 40 mg.,Adapted from Catapano AL,et al.,Curr Med Res Opin.,2006;22(10):20412053.,第,6,周时患者的达标率,%,95,85,80,75,70,LDL-C,目标,100 mg/dL(2.6 mmol/L),0,依折麦布,/,辛伐他汀,瑞舒伐他汀,90,100,10/40 mg,(n=117),20 mg,(n=119),10/20 mg,(n=121),10 mg,(n=125),10/80 mg,(n=127),40 mg,(n=106),83.5%,a,72.8%,91.5%,a,84.0%,95.3%,a,90.6%,10/2010/80 mg,(n=365),1040 mg,(n=350),90.1%,b,82.0%,亚组分析,心肾保护（,SHARP,）研究,中位随访,4.9,年,随机分组,（,9438,）,随机分组,（,886,）,依折麦布,10mg/,辛伐他汀,20mg,（,4193),辛伐他汀,20mg,（,1054),安慰剂,（,4191,）,未再次随机分组,（,168,）,依折麦布,/,辛伐他汀,（,4650),安慰剂,（,4620,）,0,1,2,3,4,5,随访年数,0,5,10,15,20,25,事件发生率（,%,）,风险比,0.83(0.74 0.94),Logrank 2P=0.0022,安慰剂,依折麦布,/,辛伐他汀,Sharp,研究：主要动脉粥样硬化事件,10,20,30,40,50,60,LDL,C,降低,%,0,他汀,10 mg,20 mg,40 mg,80 mg,他汀,10 mg,+,益适纯,10 mg,额外的,LDL-C,降低,:,一步还是三步,?,+6%,+6%,+6%,+25%,双重抑制 显著降低,LDL-C,Adapted from Stein E Eur Heart J Suppl 2001;3(suppl E):E11-E16,依折麦布,(,益适纯,),单用及与他汀类合用的安全性比较,安慰剂,益适纯,10 mg,他汀类 益适纯,+,他汀类,n=259n=262n=936n=925,总不良事件,64,68,65,64,消化道不良事件,18,21,18,17,肝功能,(,3x,正常值上限,),#,肝功能,异常,总发生,率,0,0,0.4,%,1.3,ALT,基线正常者异常率,0,0,0.3,0.4,AST 0,0,0.3,0.5,-GT1,3,3,3.6,CPK(,10 x ULN)0,0,%,0.05,无症状继续服药或停药后可逆,Davidson,JACC 2002;40:2125,；,Ballantyne,Circulation 2003;107:2409-15,；,Melani,EHJ 2003;24:717-728,；,Kerzner,AJC 2003;91:418-424,2011,年 选择性胆固醇吸收抑制剂中国专家共识依折麦布使用推荐,高胆固醇血症患者经常规剂量他汀治疗后胆固醇水平仍不能达标者，可联合应用依折麦布,严重高胆固醇血症患者可直接联合应用依折麦布与中小剂量他汀治疗,不适于或不能耐受他汀治疗的高胆固醇血症患者，可应用依折麦布治疗,单独应用依折麦布或与他汀联合用于冠心病的一级预防与二级预防,与非诺贝特联合用于以,TG,升高为主要表现的混合型血脂异常患者,纯合子,家族性高胆固醇血症以及纯合子谷甾醇血症,与,中小剂量他汀联合用于慢性肾脏疾病患者,选择性胆固醇吸收抑制剂临床应用中国专家共识,.,中华内科杂志,.2011(50):11,985-989,总 结,LDL-C,与冠心病风险高度相关，指南推荐,LDL-C,治疗目标,”,低一些更好”,现有他汀治疗的大部分高危,/,极高危患者未能达到,LDL-C,治疗目标,他汀剂量加倍的,“6”,规则,高剂量他汀的安全性问题,他汀单药治疗打破血浆胆固醇水平在体内的平衡：肠道吸收代偿性增加,通过独特的作用机理，益适纯联合他汀治疗提供强效安全的降,LDL-C,方案,较他汀单药治疗更有效降低,LDL-C,益适纯,单药或与他汀类药物联合应用具有良好的安全性和耐受性,谢 谢！,