《依折麦布临床试验》ppt课件

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1、两项依折麦布相关临床试验解读2008年在新英格兰医学杂志于3月和9月分别发表了ENHANCE和SEAS研究结果ENHANCE辛伐他汀单用或与依折麦布联用治疗家族性高胆固醇血症发表在：新英格兰医学杂志(NEJM)2008;358;1431-43研究假设依折麦布与大剂量辛伐他汀联用在改善IMT方面较辛伐他汀单用更有效Kasteleinetal,ENHANCENEJM2008;358;1431-43ENHANCE研究设计363例患者辛伐他汀80mg+安慰剂随机024月36912151821随机前阶段FH:LDL-C≥210mg/dL筛选/贝特类洗

2、脱期安慰剂导入/药物洗脱期周-6-10to-7357例患者辛伐他汀80mg+依折麦布10mgIMT评估1180ptsMonthsLDL-cholesterolSimvaEze-Simva-4006121824-50-60-700-10-20-3010PercentagechangefrombaselineP<0.01-16.5%incrementalreductionKasteleinetal,ENHANCENEJM2008;358;1431-43其他脂质参数和载脂蛋白自基线变化率Simvastatin80EZE/simva10/80Pval

3、ueTotalCholesterol-31.9±0.8-45.3±0.8<0.01LDL-cholesterol-39.1±0.9-55.6±0.9<0.01Triglycerides(median)-23.2-29.8<0.01HDL-cholesterol7.8±0.910.2±1.00.05ApoB-33.1±0.9-46.7±0.9<0.01ApoA16.9±0.86.3±0.80.56ENHANCE:对hs-CRP的疗效SimvaEze-SimvaMedianpercentchangefromBaselinep<0.01361218

4、24Months10-10-20-30-40-50-60-70-800-26%incrementalreductionBaseline24months(mg/L)(mg/L)Simva1.7(0.8-4.1)1.2(0.6-2.4)Eze-Simva1.7(0.8-3-9)0.9(0.5-1.9)Kasteleinetal,ENHANCENEJM2008;358;1431-4324个月治疗期间的cIMT纵向反复测量的分析结果ENHANCEIMT均数(mm)辛伐他汀依折麦布-辛伐他汀61218240.600.700.750.800.65月数P=

5、0.88ENHANCE：试验失败的原因?假说不成立药物失败混杂因素干扰受试者选择失败观察指标有误cIMT试验成功的关键因素ASAPSimvaLDLc-40%AtorvaLDLc-52%同样的FH人群基线cIMT减少25%斑块出现消褪!!!ENHANCESimvaLDLc-40%Simva/EzeLDLc-57%斑块逆转斑块进展cIMTmmyears0120.800.850.750.900.950.700.65ASAP-1997ENHANCE-2003CIMT是冠状动脉粥样硬化和心脏终点的替代指标？降脂干预(他汀)LowerLDLReduced

6、cardiacoutcomesDecreasecoronaryatherosclerosisIVUSCoronaryangiographyDecreasecarotidatherosclerosisCIMTBiologicalPlausibilityofCIMTassurrogateforCoronaryatherosclerosisAtherosclerosisHypertensionDyslipidaemiaSmokingDiabetesCoronaryVDCerebralVDIschaemicHDStrokesICUSCIMTCIMTW

7、hatdoesitmeasure?Atherosclerosisorageing?ProgressionofatherosclerosisSignificancetoclinicalendpoints??cerebral?cardiacCarotidarterydifferentfromcoronaryarteryDifferentsizeandstructureSomecorrelationbetweencarotidandcoronaryatherosclerosis?Similarsignificanceofriskfactors?Si

8、milarefficacyfrominterventionWhatisCarotidIntima–MediaThickness(CIMT)?CommonCaroti