优化选择降压药物.ppt

,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,P,o,w,e,r,B,a,r,中国专业,PPT,设计交流论坛,降压治疗新进展,优化选择降压药物,大学附属北京友谊医院,血压控制达标,优化治疗方案,降压治疗策略的演进,降压获益证据,中国各种心脑血管疾病死亡人数,(1991-2000,年全国疾病监测系统资料,),259240,1394971,514749,237098,81852,0,2,4,6,8,10,12,14,16,风心病,高血压,冠心病,脑血管病,其它,(10,万,),中国心血管病报告,2005.,卫生部心血管病防治研究中心,死亡人数,降低血压显著降低心脑血管事件危险,BPLTTC.Lancet 2003;362:1527-45.,-4/3 mmHg,N,20,888,0,-5,-10,-15,-20,-25,-30,-23%,-15%,-16%,-14%,-15%,心衰,卒中,冠心病,全因死亡,主要心血管事件,危险降低比例,(%),近年来的大型临床研究均一致证实,:,降压是减少心脑血管事件的硬道理,最受关注的硬终点,Kosbs JB.et al.J Clin Hypertens.2008.10:367-76.,LDL-C,水平增加,SBP,水平增加,LDL-C,水平每增加,1mg/dl,：,P,0.0001,SBP,水平每增加,1mmHg,：,P,=0.0007,140 Vs 140mmHg,：,P,=0.014,微小的血压升高，带来更多心血管事件,主要心血管事件患者百分数,微小的血压升高，带来更多卒中事件,Kosbs JB.et al.J Clin Hypertens.2008.10:367-76.,致死及非致死性卒中患者百分数,LDL-C,水平增加,SBP,水平增加,LDL-C,水平每增加,1mg/dl,：,P,=0.0395,SBP,水平每增加,1mmHg,：,P,0.0001,140 Vs 140mmHg,：,P,=0.0009,2008ESH,会议再次强调：降压治疗的主要获益源自降低血压本身,新近临床研究再次证实：降压是减少心脑血管事件的关键,血压水平与各类卒中的发生率密切相关,高血压显著增加慢性肾脏病患者心血管事件发生,2008 European Society of Hypertension annual.Berlin.,高血压病的治疗目标更加严格,首要治疗目标是长期最大限度地降低总心血管危险,控制血压和降低危险同样重要,一般患者目标血压：,140/90mmHg,（如果患者可以耐受，应降到更低水平）,糖尿病患者和高度或极高度危险患者,(,卒中、心肌梗死、肾功能不全蛋白尿,),目标血压：,130/80mmHg,为了更容易达到目标血压，应该在出现明显心血管损伤之前就开始降压治疗,Giuseppe Mancia,Co-Chairperson,Guy De Backer,et al.European Heart Journal(2007)28,14621536.,从关注诊室血压到全面关注降压质量,诊室血压数值变化,降压效果,降压的持久性,降压的平稳性,中心动脉压,降压质量,高质量降压药物可以带来更多临床获益,降压,质量,降压的持久性,降压的平稳性,其他,.,控制动脉系统血压,降压效果,高质量降压，更多获益,络活喜,:,更持久降压,VALUE,研究,24,小时动态血压亚组研究,(n=695):,络活喜,控制,服药后,20-24,小时,血压,显著优于缬沙坦,Ole Lederballe Pedersen,et al.Journal of Hypertension 2007,25:707712,*,P=0.039,2.7,mmHg,最后,4,个小时收缩压差值达,1 6 11 16,21 24,给药后时间,(,小时,),2,1,0,-,1,-,2,-,3,-,4,两组平均收缩压差值,(mmHg),缬沙坦更有效控制血压,络活喜,更有效控制血压,不同部位的血压水平有所不同,主动脉,肱动脉,140,135,130,125,120,115,0 1.0 2.0 3.0 4.0 5.0 6.0,(,年,),133.9,133.2,125.5,121.2,络活喜,组,(n=1042),阿替洛尔组,(n=1031),外周收缩压,:,平均差异,(AUC)=0.7(-0.4-1.7)mmHg,P=0.2,中心收缩压,:,平均差异,(AUC)=4.3(3.3-5.4)mmHg,P0.0001,收缩压,(mmHg),*,CAFE,研究：,2199,例来自,5,个英国,ASCOT,研究中心的患者，中心动脉压可评估人群为,2073,例：络活喜,为基础,的治疗方案组（,n=1042,）和阿替洛尔为基础的治疗方案组（,n=1031,）。随访,4,年。,ASCOT-CAF,:,络活喜更多降低中心动脉压,Williams B et al.Circulation 2006;113:1213-1225.,降压治疗模式的历史演进,序贯治疗,(sequential monotherapy),阶梯治疗,(stepped-care),联合治疗,(Combination),降压治疗选择,单药低剂量治疗,两药低剂量联合治疗,轻度血压升高,低,/,中度心血管危险,传统目标血压,显著血压升高,高,/,很高心血管危险,更低的目标血压,如果没有达到,目标血压,先前的药物全剂量,转换低剂量的,不同药物,先前联合药物全剂量,增加低剂量的,第,3,个药物,如果没有达到,目标血压,全剂量的,2-3,个,药物联合治疗,全剂量的,单药治疗,全剂量的,2-3,个,药物联合治疗,2007ESH/ESC,指南推荐的降压治疗模式,ESH2008:,联合治疗，使患者血压达标,Dr.Heribert Schunkert,：大多数患者需要联合治疗。,Prof.Roland E.Schmieder,：两类患者应该考虑联合治疗，即单药治疗或心血管高危患者经治疗不能达标的患者。,Dr.N.R.Poulter,：当需要药物联合时，应优先考虑,CCB,与,ACEI/ARB,联合,2008 European Society of Hypertension annual.Berlin.,DHP-CCBs,为基础降压联合治疗方案,优化选择的证据,中国,高血压,人群的临床特点,最主要的心血管危险是脑卒中,高血压发生和血压水平与摄盐量或饮食钠,/,钾比值较高密切有关,老年人占的比例很高,约,1/10,男性患者有嗜酒行为,钙拮抗剂治疗高血压的长处,老年患者有较好降压疗效,高钠摄入不影响降压疗效,非甾体类抗炎症药物不干扰降压作用,在嗜酒的患者有显著降压作用,适用于合并外周血管病患者,抗动脉粥样硬化作用,优化降压治疗方案，是,不同降压治疗方案在特定人群中,或者,相同降压治疗方案在不同人群中,比较长期治疗对血压控制、靶器官、代谢以及终点事件等影响的差异,。,A,voiding,C,ardiovascular Events through,COM,bination Therapy in,P,atients,LI,ving with,S,ystolic,H,ypertension,Kenneth Jamerson,1,George L.Bakris,2,Bjorn Dahlof,3,Bertram Pitt,1,Eric J.Velazquez,4,and Michael A.Weber,5,for the ACCOMPLISH Investigators,University of Michigan Health System,Ann Arbor,MI,1,;University of Chicago-Pritzker School of Medicine,Chicago,IL,2,;Sahlgrenska University Hospital,Gothenburg,Sweden,3,;Duke University School of Medicine,Durham,NC,4,;SUNY Downstate Medical College,Brooklyn,NY,5,ACCOMPLISH:,研究设计,Jamerson KA et al.,Am J Hypertens,.2003;16(part2)193A,*Beta blockers;alpha blockers;clonidine;(loop diuretics).,14 Days,Day 1,Month 1,Month 2,Year 5,Screening,Amlodipine 5 mg+benazepril 20 mg,Randomization,Benazepril 40 mg+HCTZ 12.5 mg,Benazepril 40 mg+HCTZ 25 mg,Free add-on antihypertensive agents*,Month 3,Free add-on antihypertensive agents*,Amlodipine 5 mg+benazepril 40 mg,Amlodipine 10+benazepril 40 mg,Benazepril 20 mg+HCTZ 12.5 mg,Titrated to achieve BP140/90 mmHg;130/80 mmHg in patients with diabetes or renal insufficiency,收缩压变化,mm Hg,Month,57315387520649994804428525201045,57095377515449804831428625941075,Patients,ACEI/HCTZ,N=5733,氨氯地平,/ACEI,N=5713,*,Mean values are taken at 30 months F/U visit,129.3 mmHg,130mmHg,差值,0.7 mmHg p0.05*,DBP:71.1,DBP:72.8,基线,控制率,37.2,37.9,ACCOMPLISH:,起始为联合治疗的控制率,ACEI/HCTZ,N=5733,控制率,(%),氨氯地平,/ACEI,N=5713,10,20,30,40,50,60,70,80,90,78.5,81.7,P0.001,随访,30,月时,对照组为,140/90 mmHg,首要终点的,KAPLAN-MEIER,曲线,累积事件发生率,HR(95%CI):0.80(0.72,0.90),20%Risk Reduction,到达首发,CV,事件的时间,(,天,),p=0.0002,ACEI/HCTZ,氨氯地平,/ACEI,650,526,.0,中期 数据,Mar 08,20%,0.5,1.0,2.0,首要终点的分析,复合,CV,死亡率,/,发病率,CV,死亡率,非致死性心梗,非致死性卒中,因不稳定性心绞痛入院,冠脉重建术,心脏复苏后猝死,Incidence of adjudicated primary endpoints,based upon cut-off analysis date 3/24/2008,(Intent-to-treat population),Risk Ratio(95%),氨氯地平,/ACEI,更好,ACEI/HCTZ,更好,0.80(0.720.90),0.81(0.62-1.06),0.81(0.63-1.05),0.87(0.67-1.13),0.74(0.49-1.11),0.85(0.74-0.99),1.75(0.73-4.17),中期 数据,Mar 08,结论,平均研究观察,30,个月后,总体血压控制率从,37%,增加到,80%,平均,SBP,从,145,下降到,130,mmHg,50%,患者只用单药复方治疗控制血压,.,经过平均,39,月的随访,氨氯地平,+ACEI,优于,ACEI+,利尿剂,CV,发病率,/,致死率下降,20%,(p=0.0002),CV,一级硬终点,(CV,死亡,卒中及心梗,),下降,20%,(p=0.007),专家评论,DR.MICHAEL WEBER,根据,ACCOMPLISH,研究结果，应该肯定的是,:,利尿剂在高血压治疗策略中的地位会被改变,DHP-CCB,（如络活喜）会被推荐为高血压治疗策略中必不可少的一部分,Im sure that recommendation will change.it will take away the recommendation for diuretics,and adding the calcium-channel blocker will invariably be a part of that.“Michael Weber,关注几个显著的事实,ASCOT,和,ACCOMPLISH,研究,均提前终止,ASCOT,和,ACCOMPLISH,研究,均全面更多获益,ACCOMPLISH,：血压控制率：,37%,VS,80%,ACCOMPLISH,：,血压和获益,0.7mmHg,VS,20%,ASCOT,和,ACCOMPLISH,均因络活喜而更多获益,欧洲最大的高血压研究,-ASCOT,A randomised controlled trial of the prevention of CHD and other vascular events by BP and cholesterol lowering in a factorial study design,-10 1.5 3 6,*,12 18 24 Final,ASCOT-BPLA,研究设计,络,10 mg+,培哚普利,8,mg,络 5,mg,络,10 mg+,培哚普利,4,mg,络,10 mg,阿 50,mg,阿,100 mg,阿,100 mg+BFZ 1.25 mg,阿,100 mg+BFZ 2.5 mg,络活喜组,阿,100 mg+BFZ 2.5 mg+,多沙唑嗪,GITS 4mg,络,10 mg+,培哚普利,8,mg+,多沙唑嗪,GITS 4mg,阿替洛尔组,筛选,随机,*患者每 6 个月随访一次,络,10 mg+,培哚普利,8,mg+,多沙唑嗪,GITS 8mg,阿,100 mg+BFZ 2.5 mg+,多沙唑嗪,GITS 8mg,选择性加量至目标,BP140/90 mmHg(,糖尿病,BP130/80mmHg),月,Add others,Add others,Add others,e.g.,moxonidine/spironolactone,随机前2/3患者接受降压治疗,Sever PS,et al,for the ASCOT investigators.,J Hypertens.,2001;19:1139-1147.,ASCOT-BPLA：,络活喜组更好地降低血压,mm Hg,60,80,100,120,140,160,180,Time(years),Baseline,0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,5.5,阿替洛尔,苄氟噻嗪,络活喜,培哚普利,137.7,136.1,79.2,77.4,平均差值,1.9mmHg,Last visit,平均差值,2.7mmHg,SBP,DBP,163.9,164.1,94.8,94.5,P0.001,P0.001,Number at risk,氨氯地平,培哚普利 96399475 9337 9168 8966 7863,阿替洛尔,苄氟噻嗪 96189470 9290 9083 8858 7743,0.0,1.0,2.0,3.0,4.0,5.0,Years,0.0,1.0,2.0,3.0,4.0,5.0,HR=0.90(0.791.02)p=0.1052,阿替洛尔,苄氟噻嗪,(No.of events=474),氨氯地平,培哚普利,(No.of events=429),%,络活喜更多获益：,更多减少非致死性心梗和致死性冠,心,病,10%,5,.,5,年,络活喜更多获益,:,更多减少,全因死亡,Dahlf B et al.Lancet 2005:366;895-906.,危险降低,11,%,全因死亡患者百分比,%,Number at risk,氨氯地平,培哚普利 96399483 9331 9156 8972 7863,阿替洛尔,苄氟噻嗪 96189461 9274 9059 8843 7720,氨氯地平为基础的降压方案,(n=9639,事件数,738),0.0,1.0,2.0,3.0,4.0,5.0,Years,0.0,2.0,4.0,6.0,8.0,10.0,阿替洛尔为基础的降压方案,(n=9618,事件数,820),HR=0.89(0.810.99),P=0.0247,ASCOT:,与活性药物相比,以氨氯地平为基础的降压方案仍可显著降低全因死亡危险,11,%,络活喜更多获益,:,更多,减少心血管死亡,ASCOT:,与活性药物相比,以氨氯地平为基础的降压方案仍可显著降低心血管死亡危险,24,%,Dahlf B et al.Lancet 2005:366;895-906.,患者数,氨氯地平,培哚普利,96399544 9441 93229167 8078,阿替洛尔,苄氟噻嗪,96189532 9415 92619085 7975,0.0,1.0,2.0,3.0,4.0,5.0,0.0,0.5,1.0,1.5,2.0,2.5,3.0,3.5,氨氯地平组,(263,个事件,),阿替洛尔,组,(342,个事件,),HR=0.76(0.650.90),P=0.0010,Years,危险降低,24,%,络活喜更多获益：,更多减少致死及非致死性,脑,卒中,Number at risk,氨氯地平,培哚普利 96399483 9331 9156 8972 7863,阿替洛尔,苄氟噻嗪 96189461 9274 9059 8843 7720,0.0,1.0,2.0,3.0,4.0,5.0,Years,0.0,1.0,2.0,3.0,4.0,5.0,氨氯地平,培哚普利,(No.of events 327),阿替洛尔,苄氟噻嗪,(No.of events 422),HR=0.77(0.660.89),p=0.0003,%,23%,二级终点,所有终点总结：络活喜组全面胜出,The area of the blue square is proportional to the amount of statistical information,络活喜,培哚普利更好,阿替洛尔,苄氟噻嗪更好,0.50,0.70,1.00,1.45,主要终点,Non-fatal MI(incl silent)+fatal CHD,次要终点,Non-fatal MI(exc.Silent)+fatal CHD,Total coronary end pointTotal CV event and proceduresAll-cause mortalityCardiovascular mortalityFatal and non-fatal strokeFatal and non-fatal heart failure,3,级终点,Silent,MI,Unstable anginaChronic stable anginaPeripheral arterial diseaseLife-threatening arrhythmiasNew-onset diabetes mellitusNew-onset renal impairment,事后分析,Primary end point+coronary revasc procs,CV death+MI+stroke,2.00,Unadjusted Hazard ratio(95%CI),0.90(0.79-1.02),0.87(0.76-1.00),0.87(0.79-0.96),0.84(0.78-0.90),0.89(0.81-0.99),0.76(0.65-0.90),0.77(0.66-0.89),0.84(0.66-1.05),1.27(0.80-2.00),0.68(0.51-0.92),0.98(0.81-1.19),0.65(0.52-0.81),1.07(0.62-1.85),0.70(0.63-.078),0.85(0.75-0.97),0.86(0.77-0.96),0.84(0.76-0.92),ACTION,NORDIL,INSIGHT,STOP-2-A,STOP-2-C,ALLHAT-A,ALLHAT-D,INVEST,CONVINCE,ASCOT,VALUE,Syst-Eur,Syst-China,IDNT-pbo,IDNT-Irbe,CCB,与对照药物收缩压差值,(mm Hg),-5 0 5,10 15,0.50,0.75,1.00,1.25,1.50,冠心病的相对风险比,William J.Elliott,et al.Circulation 2006;113:2763-2772,降压药物临床研究荟萃分析显示：不是所有,CCB,研究均符合降低血压减少冠心病事件的规律,其他,CCB,的临床研究,氨氯地平的临床研究,结 束 语,降压治疗研究正向,优化联合治疗方案和治疗药物的方向转移。,血压控制达标率、不良反应和终点事件发生,率等是优化选择的主要标准。长效,DHP-CCBs,将可能成为降压联合治疗优化方案的基础药物。,谢谢！,