代文高品质降压课件

,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,1-,*,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,代文高品质降压,代文：,全球处方量第一的,ARB,代文：糖尿病伴高血压治疗的理想选择,1.高品质强效降压,2.预防新发糖尿病,3.强效降低尿蛋白,4.优良的耐受性及平安性,代文：高品质降压的典范5S五大优势,Adapted from:de Gasparo et al.,Pharmacol Rev.,2000;52:415,ARB,类药物,代文,作用示意图,血管紧张素,I,血管紧张素,肝,AT,1,AT,2,血管紧张素,II,代文,血管收缩,血管增生,醛固酮分泌,心肌细胞增生,交感张力增加,炎症,氧化应激,血管舒张,抗增殖作用,凋亡,代文,通过阻断血管紧张素,II,与,AT1,受体结合阻断血管收缩、醛固酮分泌、交感张力增加等，从而起到降压作用。,代文,：,AT1受体选择性最高的ARB,1000,代文,厄贝沙坦,替米沙坦,氯沙坦,坎地沙坦,Siragy AJH 2002,30000,8500,3,000,10000,AT1/AT2,受体选择性,1000,依普沙坦,代文,降压疗效与氨氯地平相同,4,周时血压平均下降值,(mmHg),Palatini et al.,J Hypertens,2001;19:1-6,舒张压,收缩压,代文,80mg,氨氯地平,5mg,代文,80mg,氨氯地平,5mg,P=NS,P=NS,-9.1,-19.5,-10.3,-20.2,不同,ARB,治疗后的血压下降值,(mmHg),舒张压,-9.8,-6.9,收缩压,-14.1,-9.9,代文,80mg,氯沙坦,50mg,厄贝沙坦,150mg,代文,80mg,氯沙坦,50mg,厄贝沙坦,150mg,-13.8,-9.9,-7.9,-10.8,坎地沙坦,8mg,坎地沙坦,8mg,拉丁方试验证实代文,降压强效性,Fogari et al.,Curr Ther Res,2000;61(10):669-679,P0.05,P=NS,P0.05,P=NS,代文,：真正长效的降压药物,美国,FDA,要求降压药物的谷峰比值必须大于,0.5,才能一天一次使用,代文,和氨氯地平是真正的长效降压药，有助于减少凌晨心血管事件发病率。,1.,Donnelly R,et al.Clin Pharmacol Ther,1993,54:303,2.Vaur L,et al.Cardiovasc Pharmacol,1995,26:127,3.Fogari R,et al,Curr Ther Res,1999,60:165,0.3,0.5,0.6,0.7,0.49,0.68,依那普利,代文,氨氯地平,动脉血压,T/P,比值,阿替洛尔,0.4,0.40,雷米普利,氯沙坦,0.52,0.65,0.50,低,T/,P,高,T/P,中,T/P,长效平稳,代文,降压更平稳的ARB,P0.001 vs.,氯沙坦和替米沙坦；*,P0.01 vs.,氯沙坦和替米沙坦,代文、氯沙坦和替米沙坦治疗2周和4周后，,收缩压收缩压和舒张压(舒张压)的平滑指数SI,代文,组收缩压和舒张压的平滑指数，在2周和4周时均显著高于氯沙坦和替米沙坦,Fogari R,et al.Current Therapeutic Research 2002;63(1):1.,0,0.25,0.50,0.75,1.00,1.25,1.50,2周,4周,2周,4周,收缩压,舒张压,1.19*,0.70,0.61,1.29*,0.98,1.04,0.83,0.72,1.18,1.29,1.40*,1.45*,平滑指数,代文,氯沙坦,替米沙坦,危险因子 Tecumseh BP 试验,正常血压,临界高血压,P,（n=822),（n=124),总胆固醇(mg/dL),176,190,0.0001,高密度胆固醇(mg/dL),43,40,0.001,甘油三脂(mg/dL),95,135,0.0001,胰岛素(,U/AdL),12,18,0.0001,血糖(mg/dL),92,95,0.001,胰岛素/血糖比,0.155,0.200,0.0001,腰臀比,0.83,0.86,0.005,Julius S,et al;,JAMA,1990;264:354-358.,胰岛素抵抗在轻度高血压患者已经出现,临界高血压指收缩压140159,mmHg,，,舒张压9094,mmHg,100,90,80,70,60,50,40,30,无事件发生存活概率(%),发生事件的时间(年),0,3,6,9,12,15,Verdecchia P et al.,Hypertension.,2004;43:963969.,无糖尿病,新发糖尿病,既往患糖尿病,新发糖尿病患者与糖尿病患者 心血管事件危险相同-比非糖尿病患者高3倍,VALUE:代文,显著降低高血压患者新发糖尿病,新发糖尿病(%,治疗组中病人比例),0,2,4,6,8,10,12,14,缬沙坦为根底治疗组,(n=5254),氨氯地平为根底治疗组,(n=5168),13.1%,16.4%,用缬沙坦后风险降低23,16,18,P,0.0001,Lancet.2004,蛋白尿是糖尿病总体死亡率和心血管死亡率的独立危险因素,1.0,0.9,0.8,0.7,0.6,0.5,0,1,2,3,4,5,6,(,年,),存活率,(,总体,死亡率,),正常,(n=191),微量,白蛋白尿,(n=86),大量,白蛋白尿,(n=51),MA Gall,et al.Diabetes 1995;44:1303-1309,P0.01,正常,vs.,微量和,大量白蛋白尿,P0.05,微量,vs.,大量,白蛋白尿,ARB的肾脏保护优势,Ang II,Ang II,=AT,1,受体,=AT2,受体,入球动脉,出球动脉,以,AT2,为主,以,AT1,为主,与ACEI相比：,抑制旁路产生的血管紧张素II的有害作用,AT1被阻断后，血管紧张素II将可以更多地与AT2受体结合发挥有益的效应，舒张血管。因此，ARB不会导致肾小球内压力骤然下降，肾小球滤过压得以维持。,不会产生ACEI导致的咳嗽,致血肌肝异常增高的不良反响轻,致血钾升高的不良反响轻,保护心血管系统,RENAAL:ARB可明显降低尿蛋白,氯沙坦平均剂量85.5mg/日初始降压剂量的1.7倍,月,相对基线，蛋白尿的中位百分比改变,P,=0.0001,总体降低,35%,0,12,24,36,48,40,20,0,-20,-40,抚慰剂,氯沙坦,N,Engl J Med,2001;345:861-9,BP,目标值：,140/90mmHg,IRMA II：大剂量,ARB,降低尿白蛋白效果更佳,有效剂量300mg初始降压剂量的2倍,相对基线改变,%,9%,-6%,-46%,3,6,12,18,24,20,10,0,-10,-20,-30,-40,-50,N,Engl J Med,2001;345:870-8,抚慰剂,厄贝沙坦,300 mg,厄贝沙坦,150 mg,随访月,NS,P,0.001,BP,目标值：,135/85mmHg,低剂量缬沙坦降低尿白蛋白的作用,有效剂量40mg初始降压剂量的0.5倍,Suzuki k,et al.Diabetes Research and Clinical Practice 2002;57:179-83,UAE,(g/min),P,0.01,n=14,MARVAL:代文与氨氯地平两组降压疗效相同代文显著降低白蛋白排泄AER,Viberti G,Wheeldon NM,et al.Circulation.2002;106:672-8,-11.2,-6.6,-11.6,-6.5,SBP,DBP,与基线相比,24,周,平均,BP,变化,BP,(,mm Hg),0,4,8,12,18,24,-60,-40,-20,0,20,(,p 0.001),-8%,-,44%,AER,的变化,时间,(,周,),(%),代文,氨氯地平,代文,氨氯地平,代文,组有更多患者恢复至正常尿白蛋白尿水平,Giancarlo Viberti,et al.Circulation.2002;106:672-8,恢复至正常白蛋白尿*水平的患者,0,5,10,15,20,25,30,35,14.5%,29.9%,(%),代文,氨氯地平,P,=0.001,与氨氯地平相比,*定义为,UAER 20,g/min,正常血压亚组代文,显著仍可降低尿白蛋白排泄率,Giancarlo Viberti,et al.Circulation.2002;106:672-8,0,40,80,120,基线,4,8,12,18,24,p,4000,2.3,2,0,5,10,15,20,25,代文,抚慰剂,因副作用而中断治疗率,代文对男性性生活质量有明显的改善作用，而受体阻滞剂卡维地洛那么明显降低性生活质量。,Fogari R,et al.American Journal of Hypertension 2001;14:27.,6,卡维地洛,代文,安慰剂,第4周,第一次,安慰剂,第一次,安慰剂,第16周,第4周,第16周,交叉,2,4,8,10,12,代文,唯一被证实改善男性性生活质量的抗高血压药物,高品质强效降压,预防新发糖尿病,优良的耐受性及平安性,代文,II,型糖尿病伴高血压治疗,-,金标准,强效降低尿蛋白,危险因素,糖尿病,高血压,动脉粥样硬化,左室肥厚,心肌梗死,左室重构,心室扩张,充血性,心力衰竭,终末期心脏病死亡,Adapted from Dzau V,Braunwald E.,Am Heart J,.1991;121:1244-1263.,NAVIGATOR,VALUE,VALIANT,Val-HeFT,代文,全面干预心血管疾病进展,FDA,批准,心衰适应症,FDA,批准,心梗后适应症,给予生命,力量和保护,