高血压伴糖尿病肾病治疗优选.ppt

Slide Title,Body Text,Second Level,Third Level,Fourth Level,科素亚（氯沙坦钾）,高血压伴糖尿病肾病的优选,氯沙坦,高血压伴糖尿病肾病的优选,流行病学及危害,高质量降压,出色降低蛋白尿,降低终末期肾病（,ESRD),风险,流行病学,1.2007,版中国,2,型糖尿病防治指南,.,中华内分泌与代谢杂志,2008;24:2a-1-23.,；,2.WY Yang,et al.,N Engl J Med 2010;362:1090-1101,.,糖尿病患病率（,%,）,(n=30,0000),(n=21,0000),(n=4,3000),(n=10,0000),(n=46,239),过去,20,年间，我国糖尿病患病率显著上升,。,1/3,患发展为糖尿病肾病，,94%,糖尿病肾病患者合并高血压。,高血压增加糖尿病肾病患者,ESRD,或死亡的风险,(mmHg),Bakris G,et al.,Arch Intern Med 2003;163:1555-1565.,P=0.06,P0.001,P0.001,RENAAL,研究,氯沙坦钾,高血压伴糖尿病肾病的优选,流行病学及危害,高质量降压,更出色降低蛋白尿,降低终末期肾病（,ESRD),风险,糖尿病肾病患者的降压治疗,一致推荐,ARB,为一线治疗药物,K/DOQI,慢性肾病高血压和降压药物指南,JNC7,2007,ESC/ESH,高血压指南,2010 ADA,美国糖尿病协会指南,K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease,The seventh report of the joint national committee on Prevention,Detection,Evaluation,and treatment of High Blood Pressure.,Mancia G,et al.,Journal of Hypertension 2007,25:11051187.,American Diabetes Association.Diabetes Care 2010;33(Supl 1):S11-S61.,氯沙坦钾,强效降压,平稳降压,持久降压,高质量降压,氯沙坦钾,Bang LE,et al.Blood Pressure 2007;16:392-397.,LIFE,研究,平稳降压，具有较高的谷峰比,(T/P,值,),Oparil,.J Clin Hypertens;,2001;,3(5):283-318.,不同药物治疗后的降压谷峰比（,T/P,值）,收缩压,舒张压,氯沙坦钾,50mg qd,缬沙坦,80mg qd,厄贝沙坦,150 mg qd,OPARIL,研究,双重阻断，更强、更平稳、更持久降压,氯沙坦钾母体,EXP3174,AT,1,受体,氯沙坦钾与,EXP3174,均能阻断,AT,1,受体,，且作用时间持久，从而达到高效的降压作用。,竞争性阻断,非竞争性阻断,Goa KL,Wagstaff AJ.,Drugs.,May 1996;51(5):820-845.,氯沙坦钾,高血压伴糖尿病肾病的优选,流行病学及危害,高质量降压,更出色降低蛋白尿,降低终末期肾病（,ESRD),风险,Schiller et al,1999,dePablos Velasco et al,1998,Buter et al,2000,Esmatjes et al,2001,Lozano et al,2001,Ersoy et al,1999,Kosicka et al,1999,LaCouciere et al,2000,Grinstein et al,1999,Hortal et al,1998,Fauvel et al,1996,Erley et al,1995,Bauer et al,1995,Chan et al,1995,尿白蛋白,(mg/,天）,2型糖尿病,1,型糖尿病,肾移植,高血压,N=29,N=12,N=9,N=10,N=40,N=194,N=103,N=15,N=18,N=422,N=14,N=8,N=40,N=14,21,30,37,57,83,89,92,100,101,115,153,188,212,15,40,39,45,60,50,69,66,55,94,174,101,348,22,15,0,50,100,150,200,250,300,氯沙坦钾有效降低各种肾脏疾病微量白蛋白尿,Chan JC et al,Am J Nephrol,1997;17(1):72-80.,Bauer JH et al,J Hum Hypertens,1995;9:237-243.,Erley CM et al,Clin Nephrol,1995;43(Suppl 1):S8-S11.,Schiller A et al Nephrol Dial Transplant 1999;14(9):A63.,Grinstein et al,Am J Kidney Dis,1999;33(4):A28.,Lacourcire Y et al,Kidney Int,2000;58(2):762-769.,Kosicka T et al,J Hum Hypertens,1999;13(Suppl 3):S24.,Esmatjes E et al,Nephrol Dial Transplant,2001;16(Suppl 6):1-4.,Buter H et al,Diabetic Med,2000;17:550-552.(Letters).,de Pablos Velasco PL et al,Clin Drug Investi,1998;16(5):361-370.,Fauvel JP et al,J Cardiovasc Pharmacol,1996;28:259-263.,Hortal L et al,Transplant Proc,1998;30(5):2127-2128,Ersoy A et al,Nephrol Dial Transplant,1999;14(9):A283.,Lozano et al,Nephrol Dial Transplant,2001;16(Suppl 6):1-5.,氯沙坦钾,有效降低高血压伴,2,型糖尿病患者蛋白尿,Jose V.Lozano.Nephro Dian Transplant;2001,Lozano,研究,*氯沙坦钾治疗后与基线相比,p,0.0001,；,患者基线水平,UAE,氯沙坦钾治疗,6,个月后,UAE,11585,6655,显著降低患者微量白蛋白尿，治疗,6,个月后，,25%,患者尿蛋白排泄恢复正常,UAE,水平,(mg/24h),氯沙坦钾,显著降低各种肾功能阶段蛋白尿,Rumuzzi G,et al.J Am Soc Nephrol.2004;15:3117-3125,48,氯沙坦钾,+,常规治疗,安慰剂,+,常规治疗,血清肌酐,mg/dl,0.9-1.6,1.6-2.0,2.1-3.6,40,30,20,10,0,-10,-20,-30,-40,-50,-60,0,12,24,36,48,0,12,24,36,48,0,12,24,36,40,30,20,10,0,-10,-20,-30,-40,-50,-60,40,30,20,10,0,-10,-20,-30,-40,-50,-60,蛋白尿与基线的变化%,蛋白尿以晨尿标本的尿白蛋白:肌酐比率计算,RENAAL,研究,氯沙坦钾,持续显著降低蛋白尿,Shahinfar S,et al.Expert Opin Pharmacother 2006;7(5):623-630,月,0,12,24,36,48,60,蛋白尿与基线的变化%,40,20,0,20,40,35%,P0.001,31%,P0.001,39%,P0.001,35%,P0.001,29%,P0.001,3,个月,3.5,年,1,年,6,个月,安慰剂,+,常规治疗,氯沙坦钾,+,常规治疗,RENAAL,研究,时间,(,月,),0,6,12,24,36,-60,-50,-40,-30,-20,-10,0,10,20,蛋白尿与基线的变化,%,Chan JCN et al.,Diabetes Care 2004;27:874879.,氯沙坦钾持续显著降低蛋白尿亚洲人群获益更多,47%,P=0.001,安慰剂,+,常规治疗,氯沙坦钾,+,常规治疗,蛋白尿以晨尿标本的尿白蛋白:肌酐比率计算,RENAAL,研究,IDNT,研究,厄贝沙坦,平均剂量,300mg,降低蛋白尿与安慰剂比,无显著性差异,Alberto Zanchettia,et al.J Hypertens 2002,，,20:20992110,RENAAL,研究：氯沙坦钾,50-100mg,降低蛋白尿优于安慰剂,氯沙坦钾,高血压伴糖尿病肾病的优选,流行病学及危害,高质量降压,更出色降低蛋白尿,降低终末期肾病（,ESRD),风险,为什么关注,ESRD,单项肾脏终点指标？,降低蛋白尿,(,中间终点,),降低,ESRD,危险,(,硬终点,),ESRD=,肾脏死亡，,对于无法实施透析或不适合肾移植患者，降低,ESRD,危险意味着,延缓,死亡。,Shahifar S,et al.Kidney Inter,2002;82S:S64-S67,Tomas MC,et al.Kidney Int.2003;63:1577-1579,月,0,12,24,36,48,0,10,20,30,安慰剂,+,常规治疗,氯沙坦钾,+,常规治疗,P(+CT),L(+CT),751,714,625,375,69,762,715,610,347,42,Brenner BM et al New Engl J Med 2001;345(12):861-86.,28%,P=0.002,RENAAL,研究,氯沙坦钾,唯一经大型临床试验证实,可显著降低,ESRD,危险的,ARB,ESRD,发生率,%,COZAAR(losartan),Nephropathy in Type 2 Diabetic Patients:RENAAL,“The primary endpoint of the study was the time to first occurrence of any one of the following events:doubling of serum creatinine,end-stage renal disease(ESRD)(need for dialysis or transplantation),or death.Treatment with COZAAR resulted in a 16%risk reduction in this endpoint(see Figure 4 and Table 3).,Treatment with COZAAR also reduced the occurrence of sustained doubling of serum,creatinine,by 25%and ESRD by 29%as separate endpoints,but had no effect on overall mortality.”,From US FDA Product Insert,初始终点：是初次发生下列事件的时间：血清肌酐加倍，终末期肾病（需要透析或肾移植）或死亡。,1.,氯沙坦钾治疗减少,16%,的综合终点。,2.,氯沙坦钾治疗也持续减少了,血清肌酐加倍,25%,和,终末期肾病,29%,作为独立终点,US FDA 氯沙坦钾产品说明书,总 结,氯沙坦钾双重阻断,AT,1,，能够强效、持久、平稳的高质量降压,氯沙坦钾有效降低蛋白尿,氯沙坦钾可降低各种基线水平蛋白尿,肾功能各阶段（,血清肌酐,0.9-3.6mg/dl,）,均显著降低蛋白尿,各种人群蛋白尿平均降低,35%,，亚洲人群获益更多（,47%,）,持续出色降低蛋白尿,氯沙坦钾,唯一经循证医学证实可显著,降低,ESRD,危险,的,ARB,谢 谢,