谁将从ARB中获益谭宁广东省人民医院.pptx

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Level,#,谁将从,ARB,中获益,?,谭宁,广东省人民医院,“,CV,高危患者,”,发生心血管事件（如,MI,或卒中）的风险高,CV,高危患者包括：,动脉粥样硬化病的患者，例如有以下病史：,心肌梗死,卒中或一过性脑缺血发作,外周动脉疾病,有靶器官损害的,2,型糖尿病患者,有多种危险因素的患者,这些高危患者是心血管事件后备军,中国心血管病报告,2008,高血压,1.6,亿,冠心病,560,万,糖尿病,4000,万,卒中,700,万,如何挽救高危患者？,我们不应该袖手旁观！,-,ARB,在高危患者中的心血管保护作用,有多种危险因素的患者,CV,危险因素,:,越来越多见,肥胖,(BMI30):从,2005,年到,2015,年，将上升,75%(,成人肥胖从,4,亿增加到,7,亿,),超重,(BMI 25-30):,从,2005,年到,2015,年，将上升,44%(,成人超重从,16,亿增加到,23,亿,),2,型糖尿病,:,从,2000,年到,2030,年，将上升,114%(,从,1.71,亿增加到,3.66,亿,),高血压,:,从,2000,年到,2025,年，将上升,56%(,从,10,亿增加到,15.6,亿,),CV,危险因素,居,全球主要死因,之列,高血压,儿童超重,不安全的性行为,蔬菜和水果吃得少,超重和肥胖,运动少,饮酒,室内空气污染（固体燃料）,可归因的死亡,吸烟,高胆固醇,0,2000,4000,6000,8000,Lopez et al.Lancet 2006;367:1747-57,INTERHEART,研究,：,存在多种危险因素,，,风险,则增加,Yusuf et al.Lancet 2004;364:937952,鼓励生活方式,的改变,使用经,验证,可降低,CV,事件风险的药物,改善饮食,多运动,戒烟,他汀类,抗血小板制剂,降糖药,降压药,(RAS,阻断,剂,),受体阻滞剂,RAAS,阻滞剂,阻断疾病进展可预防,CV,事件,STOP 1 1991,LINILOQ 1991,BBB 1994,HOT 1998,CAPPP 1999,STOP 2 1999,NORDIL 2000,PRESERVE 2001,LIFE 2002,REGAAL 2002,ASCOT-LLA 2003,ASCOT-BPLA 2005,PIXCEL 2005,JIKEI HEART 2007,ACCOMPLISH 2008,PRoFESS 2008,ALLAY 2008,KYOTO HEART 2009,SHOT-T,2010,1983,CCB,受体,阻滞剂,受体,阻滞剂,利尿剂,其他,RAAS,阻断,的基石,ARBs,阻断,RAAS,可考虑,作为降压治疗的基础并用于高危,CV,患者,血管紧张素原,血管紧张素,-,AT1,受体,肾素,肾素,-,血管紧张素系统成人中的平衡问题,血管收缩,增加心肌收缩力,增加心血管肥大,增加液体和电解质潴留,炎症,细胞凋亡,血管舒张,逆转心血管肥大和纤维化,逆转液体和电解质渚留,抗炎,增加一氧化氮（间接,B2,受体）,再生，保护,血管紧张素,-,血管紧张素转换酶,(ACE),AT,2,受体,ARB,是目前唯一被证实显著降低,IGT,患者新发糖尿病风险的降压药物,0,1,2,3,4,5,6,50,40,30,20,10,0,ARB,安慰剂组,糖尿病发生率（,%,）,随机化后随访时间（年）,新发糖尿病风险显著降低,HR:0.86,95%CI:0.800.92,缬沙坦组,Vs,安慰剂组：,P,300,，且血清肌酐,1.3-3.0mg/dl(N=,1,5,1,3),氯沙坦,vs.,安慰剂,ARB,较安慰剂显著降低,T2DN,患者肌酐倍增、,ESRD,或死亡复合终点,16%,3.4,年,MARVAL,2002,年,有微量蛋白尿的2型糖尿病患者,(N=332),缬沙坦,vs.,氨氯地平,血压控制相当，,ARB(,缬沙坦,),较,CCB,显著降低,T2DM,合并微量白蛋白尿患者尿白蛋白尿排泄率,(-44%vs.-8%,，,P,雷米普利,(,耐受性,),T+R=R(,疗效,),T T+R(,耐受性,),NEJM 2008;358:1547-1549,ONTARGET,卒中的患者,RAS,阻断对卒中的影响,:ARBs,和,ACE-,I,的荟萃分析,MI,心血管死亡率,全因死亡率,卒中,ARB,疗效佳,ACE,-I,疗效佳,Reboldi et al.,J Hypertension,2008;26:12821289,研究,(N=63,409):ELITE;ELITE-II;OPTIMAAL;DETAIL;VALIANT;ONTARGET,Spansk studie ARB less severe strokes,卒中前,ARB,治疗,对急性脑梗塞有益,Spansk studie ARB less severe strokes,多元回归分析显示,：,既往的,ARBs,治疗与卒中严重度,程度的降低,独立相关,(,OR:040;95%CI 0.24,-,0.65,p0.001,),；,与不良转归呈负相关,(,OR:0.41;95%CI 0.23,-,0.78,p=0.003,),卒中中,AT2,受体的作用,卒中范围,认知,Mogi M,Horiuchi M et al.,Hypertension.48:141-8.2006,氧化应激,Iwai M,Horiuchi M et al.,Circulation.110:843-8.2004,神经分化,受损的,DNA,Li JM,Horiuchi M et al.,Mol Endocrinol.21:499-511.2007,直接神经保护作用,挽救濒临死亡的神经元,半影区的脑血流,Iwai M,Horiuchi M et al.,Circulation.110:843-8.2004,Li JM,Horiuchi M et al.,Stroke.39:2029-2036 2008,冠心病的患者,ARB,改善冠心病患者预后：,JIKEI Heart,对,JIKEI HEART,研究中,1036,例合并冠心病的心血管高危患者（缬沙坦组,n=514,，非,ARB,组,n=522,）进行亚组分析,缬沙坦较非,ARB,显著降低心脏事件发生风险,51%,缬沙坦较非,ARB,显著降低致死或非致死冠脉事件发生风险,56%,心脏事件,*,显著降低,51%,P0.0001,致死或非致死冠脉事件,*,显著降低,56%,P=0.0007,HR 0.49;95%CI 0.33-0.71,事件率（,%,）,月,非,ARB(n=522),缬沙坦,(n=514),HR 0.44,；,95%CI;0.27-0.71,非,ARB(n=522),缬沙坦,(n=514),月,事件率（,%,）,*,心脏事件：心绞痛、急性心梗、心衰,*,致死或非致死冠脉事件：心绞痛、急性心梗,Shimizu M,et al.Presented at ESC 2010.,ARB,应用于心肌梗塞的试验,心肌梗死后使用血管紧张素,II,受体拮抗剂氯沙坦最佳试验（,Optimal trial in myocardial infarction with angiotsnsin II antagonist losartan.,OPTIMAAL.2002,）,缬,沙坦治疗急性心肌梗死试验,(,Valsartan in acute myocardial infarction,VALIANT.2003,),OPTIMAAL:,试验结果,氯沙坦,（,n=2744,）,卡托普利（,n=2733,）,相对危险（,95%CI,）,P,值,总死亡率,499(18.2%),447(16.4%),1.13(0.991.28),0.069,心猝死复苏,239(8.7%),203(7.4%),1.19(0.991.43),0.072,再次心肌梗死,384(14.0%),379(13.9%),1.03(0.891.18),0.722,心血管病死亡,420(15.3%),363(13.3%),1.17(1.011.34),0.032,中风,140(5.1%),132(4.8%),1.07(0.841.36),0.587,Dickstein K,et al.Lancet 2002,Losartan 50mg qd.,并不优于,Captopril 50mg tid.,ACEIs remain first-line treatment post-MI,Primary Endpoint:,All-Cause MortalitySecondary Endpoint:,Cardiovascular Death,Other Endpoints:,Safety and Tolerability,Study Design(14,703 patients),EVENT DRIVEN (2,700 deaths),Pfeffer MA et al.Am Heart J,.2000;140:727734.,Captopril 50 mg TID,(n,4,900),Valsartan 160 mg BID,(n,4,900),Captopril 50 mg TID+Valsartan 80 mg BID,(n,4,900),Acute MI,and,either HF or LV systolic dysfunction,N=14,703,Median follow-up:24.7 months,VALIANT,Valsartan vs Captopril in Acute MI,Mortality by Treatment,Valsartan 4909 4464 4272 4007 2648 1437 357,Captopril 4909 4428 4241 4018 2635 1432 364,Valsartan+Cap 4885 4414 4265 3994 2648 1435 382,Captopril,0,0.05,0.1,0.15,0.2,0.25,0.3,0,6,12,18,24,30,36,Probability of Event,Months,Valsartan vs.Captopril:HR=1.00;P=0.982,Valsartan+Captopril vs.Captopril:HR=0.98;P=0.726,Valsartan,Valsartan+Captopril,心衰的患者,ARB,应用于心衰治疗的试验,氯沙坦心力衰竭试验（,Effects of losartan versus captopril on patients with symptomatic heart failure,.,ELITE-II.1999,）,缬沙坦心力衰竭试验,(,Val-HeFT.2001,),坎地沙坦,心力衰竭试验,(,Candesartan in heart failure:Assessment of reduction in mortality and morbidity.,CHARM.,2003,),ELITE-II,试验：研究终点小结,卡托普利组,（,n=1574,）,氯沙坦组,（,n=1578,）,校正后危险比,（,95%CI,）,P,值,主要终点,总死亡率,250(15.9%),280(17.7%),0.88(0.751.05),0.16,二级终点,猝死,/,复苏,1157.3%),142(9.0%),0.80(0.631.03),0.08,三级终点,总死亡,/,住院,707(44.9%),752(47.7%),0.94(0.851.04),0.21,副作用停药,228(14.5%),149(9.4%),65 y,NYHA II-IV,EF 40%,Losartan;50 mg qd;Captopril;50 mg tid;FU:510 deaths,Val-HeFT:,试验设计,5010 patients,18 years;EF 40%;NYHA IIIV,Diuretics(85%),Digoxin(67%),-blockers(35%),ACE inhibitors(93%),Valsartan40 mg bid titrated to160 mg bid,Randomized to,Receiving background therapy,Placebo,906,Deaths,(Combined All-cause Mortality and Morbidity),Follow up 23,月,Val-HeFT,：主要终点分析,终点,事件数,危险比,（,95%CI,）,P,值,缬沙坦组,（,n=2511,）,安慰剂组,（,n=2499,）,所有原因死亡,495,(19.7%),484,(19.4%),1.02,(0.901.15),0.800,所有原因死亡,/,病残率,723,(28.8%),801,(32.1%),0.87,(0.790.96),0.009,Val-HeFT,经治疗心衰住院危险降低,随机分组的时间（月）,1.0,0.9,0.8,0.7,危险减少,27.5%,P=0.00001,缬沙坦,安慰剂,无事件发生率,3,6,9,12,21,18,15,24,27,0,Cohn et al.AHA Scientific Sessions 2000,*Censored for death,次级终点,:,第一次因心衰住院的时间,对未服用,ACEI,的患者，代文,显著降低联合死亡率和发病率,44%,Maggioni et alJACC,2002;40:1414-1421,0.400,0.486,0.571,0.657,0.743,0.829,0.914,0,3,6,9,12,15,18,21,24,27,1.000,月,无事件概率（,%,）,代文组,(n=185),安慰剂组,(n=181),44%,366,例未服用过,ACEI,的心力衰竭患者,HR=0.56;95%Cl 0.39-0.81,p40%,ACE inhibitor treated/not treated,Primary outcome for Overall Programme:All-cause death,Primary outcome for each trial:CV death or CHF hospitalisation,Pfeffer MA,et al.Lancet 2003,362(9386):759781,Proportion with CV Death or Hospitalization for CHF,Candesartan,Placebo,ALTERNATIVE,1013,1015,831,798,434,427,122,126,929,887,1013,1015,831,798,434,427,122,126,929,887,50,40,0,0,2,3,3.5,Time(Years),30,20,10,1,50,40,0,0,2,3,3.5,Time(Years),30,20,10,1,Placebo,Candesartan,23%RR,p=0.0004,ADDED,1276,1272,1063,1013,948,906,457,422,1176,1136,1276,1272,1063,1013,948,906,457,422,1176,1136,50,40,0,Time(Years),30,20,10,2,3,3.5,1,0,2,3,3.5,1,Placebo,Candesartan,15%RR,p=0.01,PRESERVED,1514,1509,1377,1359,833,824,182,195,1458,1441,1514,1509,1377,1359,833,824,182,195,1458,1441,0,2,3,3.5,Time(Years),1,0,2,3,3.5,Time(Years),1,Placebo,Candesartan,11%RR,p=0.12,50,40,0,30,20,10,50,40,0,30,20,10,ESH,和,ESC,指南,:,风险分层以定量分析预后,表,2,风险分层以定量分析预后,其他危险因素和病史,正常,高 正常,血压（,mm Hg),1,级,2,级,3,级,没有其他危险因素,1-2,个危险因素,平均风险,平均风险,低附加风险,低附加风险,低附加风险,中附加风险,中附加风险,中附加风险,中附加风险,高附加风险,高附加风险,高附加风险,高附加风险,极高附加风险,极高附加风险,3,种或以上危险因素或,TOD,或糖尿病,高附加风险,极高附加风险,极高附加风险,极高附加风险,极高附加风险,ACC,，相关临床情况；,TOD,，靶器官损害；,SBP,，收缩期血压；,DBP,，舒张期血压,ESH,和,ESC,指南,:,风险分层以定量分析预后,ACC,，相关临床情况；,TOD,，靶器官损害；,SBP,，收缩期血压；,DBP,，舒张期血压,其他危险因素和病史,没有其他危险因素,1-2,个危险因素,3,种或以上危险因素或,TOD,或糖尿病,平均风险,平均风险,低附加风险,低附加风险,低附加风险,中附加风险,中附加风险,中附加风险,中附加风险,高附加风险,高附加风险,高附加风险,高附加风险,高附加风险,极高附加风险,极高附加风险,极高附加风险,极高附加风险,极高附加风险,极高附加风险,表,2,风险分层以定量分析预后,CCB,受体阻滞剂,受体阻滞剂,利尿剂,其他,ARB,基础治疗,采用,ARBs,阻断,RAAS,考虑作为降压治疗的基础并用于高危,CV,患者,Highest rates of antihypertensive persistence with ARBs(ISPOR),When itcomes to patient persistence with antihypertensive prescriptions,angiotensin receptor blockers(,ARB,s)seem to produce the best results,according to a German study.,The study,based on real-life data from GP practices,showed that in,Germany and France fixed-dose ARB,combinations were associated with the best persistence,whereas in the,UK simple ARBs,achieved the best results.,A total of 13,437 patients in France,68,341 in Germany,and 16,165 in the UK were identified for analysis.,ESC Congress 2011 Highlights,结论,:,谁,将从,RAS,阻滞剂,中获益,?,风险是一个从危险因素到动脉粥样硬化血栓性疾病到心衰的连续体,对于降压药（如,RAS,阻滞剂）,而言,，达到强有力的,血压,下降是降低,CV,风险的一个关键特征,个,体,风险的特征决定治疗选择：治疗应在相关患者人群中有确切的,预防,疗效！,ARB,是高血压和,CV,高,危人群,治疗的基础,ARB,在高危患者中起心血管保护作用,Thank you!,