课件：依折麦布临床试验.pptx

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Kastelein et al, ENHANCE NEJM 2008;358 ;1431-43 ENHANCE 研究设计随机前阶段随机357 例患者 辛伐他汀 80 mg + 依折麦布 10 mg FH:LDL-C ≥ 210 mg/dL 363 例患者辛伐他汀 80 mg + 安慰剂安慰剂导入/ 药物洗脱期筛选/ 贝特类洗脱期1180 ptsIMT评估-6-10 to -702124318156912周月LDL-cholesterol100-10-20P0.01-30Percentage change from baseline-40-16.5 % incremental reduction-50-60-70Simvze-SimvaMonthsKastelein et al, ENHANCE NEJM 2008;358 ;1431-43 其他脂质参数和载脂蛋白自基线变化率Simvastatin 80EZE/simva 10/80P valueTotal Cholesterol-31.9±0.8-45.3±0.80.01LDL-cholesterol-39.1±0.9-55.6±0.90.01Triglycerides (median)-23.2-29.80.01HDL-cholesterol7.8±0.910.2±1.00.05Apo B-33.1±0.9-46.7±0.90.01Apo A16.9±0.86.3±0.80.56ENHANCE: 对 hs-CRP 的疗效 Baseline 24 months (mg/L) (mg/L) Simva 1.7(0.8-4.1) 1.2(0.6-2.4) Eze-Simva 1.7(0.8-3-9) 0.9(0.5-1.9)100Simvap 0.01Eze-Simva-10-20Median percent change from Baseline-30-26 % incremental reduction-40-50-60-70-8012618324MonthsKastelein et al, ENHANCE NEJM 2008;358 ;1431-43 24个月治疗期间的cIMT纵向反复测量的分析结果0.80辛伐他汀依折麦布-辛伐他汀0.75P=0.88IMT均数 (mm)0.700.650.601218624月数ENHANCEENHANCE：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 ASAP - 19970.95ASAP斑块进展0.90Simva LDLc -40%Atorva LDLc -52%0.85ENHANCEcIMT mm0.80Simva LDLc -40%Simva/Eze LDLc -57%0.75ENHANCE - 20030.700.65斑块逆转012yearscIMT 试验成功的关键因素同样的 FH 人群基线cIMT减少25%斑块出现消褪!!! CIMT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)Lower LDLDecrease carotid atherosclerosisDecrease coronary atherosclerosisCIMTIVUSCoronary angiographyReduced cardiac outcomesBiological Plausibility of CIMT as surrogate for Coronary atherosclerosisSmokingDiabetesCIMT What does it measure ? Atherosclerosis or ageing? Progression of atherosclerosis Significance to clinical endpoints ? ? cerebral ? cardiacCarotid artery different from coronary artery Different size and structure Some correlation between carotid and coronary atherosclerosi