高血压药物联合治疗课件

,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,*,*,*,抗高血压药物的临床应用,2024/8/29,1,抗高血压药物的临床应用2023/9/41,血压水平的定义和分类（,WHO/ISH 1999）,分类,收缩压（,mmHg）,舒张压（,mmHg）,理想血压,120,80,正常血压,130,85,正常高值,130,139,85,89,1级高血压(轻度),140,159,90,9,9,亚组：临界高血压,140,149,90,94,2级高血压(中度),160,179,100,109,3级高血压(重度),180,110,单纯收缩期高血压,140,90,亚组：临界收缩期高血压,140,149,55岁,女性，65岁,吸烟,总胆固醇5.72,mmol/L,糖尿病,早发心血管病家族史（男 55岁，女65岁）,对预后有不良影响的其他因素,高密度脂蛋白胆固醇降低,低密度脂蛋白胆固醇升高,糖尿病微蛋白尿,糖耐量受损,肥胖,血纤维蛋白原升高,静息的生活方式,高危社会经济人群,高危族群,高危地区,2024/8/29,5,心血管疾病的危险因素用于危险度分层的因素对预后有不良影响的其,高血压的危险度分层,血压,1,级2级3级,I,无其它危险因素低危中危高危,II1,2,个危险因素中危中危极高危,III3,个危险因素高危高危极高危,或靶器官损害或糖尿病,IV,并存临床情况极高危极高危极高危,2024/8/29,6,高血压的危险度分层 血压2023/9/46,Stoke and usual DBP,(in 5 categories defined by baseline DBP),7 prospective observational studies: 843,events,Relative Risk of Stroke,Baseline,DBP category,Approximate mean usual DBP,4.00,2.00,1.00,0.50,0.25,1 2 3 4 5,76 84 91 98 105,mmHg,Coronary Heart Disease and usual DBP,(in 5 categories defined by baseline DBP),9 prospective observational studies: 4856 events,Relative Risk of CHD,Baseline,DBP category,Approximate mean usual DBP,4.00,2.00,1.00,0.50,0.25,1 2 3 4 5,76 84 91 98 105,mmHg,Relative risks of stroke and of coronary heart disease, estimated from combined results.,2024/8/29,7,Stoke and usual DBPRelative Ri,Framingham Heart Study,-,Risk of Cardiovascular Events by Hypertensive Status in Patients Aged 35-64 Years; 36-Year Follow-Up,Risk Ratio2.02.23.82.62.03.7 4.03.0,Excess Risk22.711.89.13.84.95.3 10.44.2,Coronary Disease,Stroke,Peripheral ArteryDisease,Cardiac Failure,Biennial Age-Adjusted Rate per 1000,Kannel WB,JAMA,1996;275(24):1571-1576.,Hypertensive Patients Are at Increased Risk for Cardiovascular Events,2024/8/29,8,Framingham Heart Study - Risk,Blood Pressure and the Risk of Coronary Heart Disease and Stroke,Baseline Diastolic Blood Pressure (mm Hg),Incidence per 1,000,CHD,Stroke,69,70-7,9,80-8,9,90-9,9,100-10,9, 110,5,10,15,20,30,40,25,35,45,Hunt, S.C. et al., in: Atherosclerosis and Coronary Heart Disease, p. 209-35,2024/8/29,9,Blood Pressure and the Risk of,血压与心血管危险荟萃分析,75,80,85,90,95,舒张压,(,mmHg),EWPHE(n=840),SYST-EUR(n=4695),SYST-CHINA(n=2394),0.28,0.24,0.20,0.16,0.12,0.08,0.04,120140160180200220240,收缩压(,mmHg),2年达到终点的危险性,Arch Intern Med 2000;160:1085,2024/8/29,10,血压与心血管危险荟萃分析75舒张压EWPHE(n=840)0,与收缩压相关危险性:,MRFIT,Adapted from Neaton JD et al.,Arch Intern Med,. 1992;152:56-64.,收缩压和舒张压与冠心病死亡率的关系,舒张压,(,mm Hg),收缩压,(,mm Hg),CHD,死亡率,100+,9099,8089,7579,7074,70,30月中风57%,总心脏事件41%,CNIT,硝苯地平 683 58月中风50%,总心脏事件44%,Syst-China,尼群地平 2367 48月中风38%,总心脏事件37%,合计 4694例,2024/8/29,33,中国钙拮抗剂的大规模临床试验 试验 药物,氨氯地平：临床试验,PRAISE：,氨氯地平,安全用于合并重度心力衰竭患者,PREVENT：,氨氯地平,显著延缓颈动脉粥样硬化；显著减少冠心病患者心血管事件及操作总和；显著减少住院费用,CAPARES：,氨氯地平,显著减少,PTCA,后患者再次,PTCA,的发生率及心血管事件总和,2024/8/29,34,氨氯地平：临床试验PRAISE：氨氯地平安全用于合并重度心力,PREVENT：,氨氯地平对,B,超测定的颈动脉内膜中层厚度（,IMT）,的作用,0,.,0,5,0,.,0,4,0,.,0,3,0,.,0,2,0,.,0,1,0,.,0,0,-,0,.,0,1,P,=,0,.,0,0,7,0,1,2,2,4,3,6,内膜中层厚度变化,(,mm),Circulation ,1999,安慰剂,氨氯地平,时间（月）,2024/8/29,35,PREVENT：氨氯地平对B超测定的颈动脉内膜中层厚度（I,PREVENT:,因不稳定心绞痛住院及主要血管操作,随访月数,所有血管重建术,安慰剂,氨氯地平,43%,P,=0.001,30.0,25.0,20.0,15.0,10.0,5.0,0.0,0,6,12,18,24,30,36,累计事件/操作发生率 (%),随访月数,记录的不稳定心绞痛/,充血性心力衰竭,安慰剂,(,n=408),氨氯地平,(,n=417),35%,P,=0.01,30.0,25.0,20.0,15.0,10.0,5.0,0.0,0,6,12,18,24,30,36,Pitt et al.,Circulation,. 2000.,2024/8/29,36,PREVENT: 因不稳定心绞痛住院及主要血管操作 随访月,PREVENT：,所有主要事件及操作的发生率,累计的事件/ 操作发生率 (%),随访月数,氨氯地平,(,n=417),31%,P,=0.01,30.0,25.0,20.0,15.0,10.0,5.0,0.0,0,6,12,18,24,30,36,安慰剂,(,n=408),Pitt et al.,Circulation,. 2000.,2024/8/29,37,PREVENT：所有主要事件及操作的发生率累计的事件/ 操,PRAISE：,前瞻性随机氨氯地平存活评估,Packer M. et al, N Engl J Med, 1996, 335: 1107-14,39%,33%,42%,38%,致命性与非致死性事件的总和,死亡率,氨氯地平,安慰剂,P=0.07,P=0.31,目的：,评价氨氯地平长期治疗重度慢性充血性心力衰竭对发病率和死亡率的影响,结果：,氨氯地平对死亡率以及心血管事件的发生率均无不良影响,2024/8/29,38,PRAISE：前瞻性随机氨氯地平存活评估Packer M.,ALAAE：,冠状动脉内膜-中层厚度降低,治疗14周,治疗26周,治疗50周,P=0.044,与基线相比*,P0.05， *P0.001,与,基,线,相,比,的,平,均,变,化,(,um),*,*,*,*,*,2024/8/29,39,ALAAE：冠状动脉内膜-中层厚度降低治疗14周治疗26周治,INSIGHT：,硝苯地平控释剂,阻断颈动脉内膜中层,(,IMT),增厚,-0.0020,0,0.0020,0.0040,0.0060,0.0080,0.0077,- 0.0007,Progression,增厚,Regression,逆转,P=0.003,利尿剂,联合用药,硝苯地平,IMT,增厚速率（毫米,/,年）,Alain Simon, et al. Circulation. 2001;103:2949-2954,2024/8/29,40,INSIGHT：硝苯地平控释剂阻断颈动脉内膜中层(IMT)增,INSIGHT：,硝苯地平控释剂,显著延缓颈动脉狭窄, 1,年, 2,年, 3,年, 4,年,0,P0.05,-0.100,-0.200,-0.300,利尿剂,联合用药,硝苯地平,颈动脉狭窄程度 (毫米),Alain Simon, et al. Circulation. 2001;103:2949-2954,2024/8/29,41,INSIGHT：硝苯地平控释剂显著延缓颈动脉狭窄 1年,硝苯地平控释剂保护高血压的肾脏功能,*,两次,测量结果，肾小球滤过率与基线值相比降低均超过,25%,1.8,4.6,p 0.0001,5,4,3,2,1,0,硝苯地平控释剂,利尿剂联合用药,肾功能损害发生率,(%),INSIGHT,试验,2024/8/29,42,硝苯地平控释剂保护高血压的肾脏功能* 两次测量结果，肾小球滤,ELSA,：,临床血压和心率的平均值,收缩压,舒张压,脉压,mmHg,心率,170,Baseline,Year 1,Year 2,Year 3,Year 4,165,160,155,150,145,140,135,130,125,mmHg,70,Baseline,Year 1,Year 2,Year 3,Year 4,65,60,55,50,bpm,Baseline,Year 1,Year 2,Year 3,Year 4,mmHg,105,Baseline,Year 1,Year 2,Year 3,Year 4,100,95,90,85,80,75,治疗,阿替洛尔,拉西地平,80,75,70,65,60,2024/8/29,43,ELSA：临床血压和心率的平均值收缩压舒张压 脉压mmHg心,事件类型,致死性心梗,非致死性心梗,所有心梗,致死性中风,非致死性中风,所有中风,其他心血管死亡,所有主要心血管事件,所有心血管死亡,所有死亡,n/1000 ptyears,0.83,3.86,4.68,0.83,3.31,3.86,0.55,9.09,2.20,4.68,n,3,14,17,3,12,14,2,33,8,17,n/1000 pt years,0.55,4.42,4.97,0.282.21,2.49,0.28,7.46,1.10,3.59,n,2,16,18,1,8,9,1,27,4,13,RR (95% CI),1.04,(0.54-2.01),0.63,(0.27-1.45),0.80,(0.49-1.33),0.49,(0.15-1.63),0.75,(0.37-1.54),阿替洛尔,拉西地平,ELSA,：,安全性分析,2024/8/29,44,事件类型RR (95% CI)阿替洛尔拉西地平ELSA：安全,研究,ELSA,BCAPS,PREVENT,SECURE,VHAS,INSIGHT,7 studies,病人,HT,VD,CHD,VD,HT,HT,VD,治疗,阿替洛尔,拉西地平,安慰剂,美托洛尔,安慰剂,氨氯地平,安慰剂,雷米普利,双氢克脲噻,维拉帕米,Co-Amilozide,硝苯地平,-GITS,安慰剂,他汀类,IMT,变化,(mm/year),0.0146,0.0057,0.041,0.029,0.011,-0.0042,0.0217,0.0137,-0.001,-0.011,0.0077,-0.0004,疗效,(mm/year),-0.0089,-0.0120,-0.0152,-0.0080,-0.0100,-0.0081,-0.02,ELSA与其他研究结果的比较,2024/8/29,45,研究病人治疗IMT变化(mm/year)疗效 (mm/yea,1受体阻滞剂,适应症：前列腺肥大,可能适应症：糖耐量异常，血脂异常,可能禁忌症：直立性低血压,主要副作用：低血压，极易产生耐药性,常用药物,哌唑嗪（,prazosin）,首剂0.5,mg，,以后15,mg tid,多沙唑嗪（,doxazosin）14 mg qd,乌拉地尔（,urapidil,） 3060,mg bid,2024/8/29,46,1受体阻滞剂适应症：前列腺肥大2023/9/446,血管紧张素受体拮抗剂（,ARB）,适应症：,ACEI,引起咳嗽,可能适应症：心力衰竭,禁忌症：妊娠，高钾血症，双侧肾动脉狭窄,常用药物,氯沙坦（,losartan,）50100,mg qd,缬沙坦（,valsartan,）80160,mg qd,依贝沙坦（,irbesartan） 150300 mg qd,替米沙坦（,telmisartan) 40 80 mg qd,2024/8/29,47,血管紧张素受体拮抗剂（ARB）适应症：ACEI引起咳嗽20,2024/8/29,48,2023/9/448,2024/8/29,49,2023/9/449,Losartan,Atenolol,RR,p,RR,p,(,n=4605),(,n=4588),(%),(%),Primary composite,*,508,588,-,13,0.021,-,15,0.009,CV mortality,204,234,-,11,0.206,-,13,0.136,Stroke,2,32,309,-,25,0.001,-,26,0.0006,MI,198,188,+7,0.491,+5,0.628,Total mortality,383,431,-,10,0.128,-,12,0.077,New,-,onset DM,*,241,319,-,25,0.001,-,25,0.001,LIFE:,Primary and Secondary Outcomes,*,For degree of LVH and Framingham risk score at randomizatio,n,*,CV mortality, stroke and MI; patients with a first primary e,vent,*,Among patients without diabetes at randomization (losartan n,=4019;,atenolol, n=3979),Dahl,鰂,B et al,Lancet,2002;359:995,-,1003.,Unadjusted,Adjusted,*,2024/8/29,50,LosartanAtenololRRpRRp(n=4605),LIFE:,Change from Baseline in LVH Regression,-,18,-,16,-,14,-,12,-,10,-,8,-,6,-,4,-,2,0,Cornell Product,Sokolow,-,Lyon,Mean change from baseline (%),Losartan,Atenolol,p0.0001,Dahl,鰂,B et al,Lancet,2002;359:995,-,1003.,10.2 %,9.0 %,15.3 %,4.4 %,p0.0001,2024/8/29,51,LIFE:Change from Baseline in L,New-Onset Diabetes,Intention-to-Treat,Losartan,Atenolol,Atenolol (N=3979),Losartan (N=4019),Study Month,0,6,12,18,24,30,36,42,48,54,60,66,0.00,0.01,0.02,0.03,0.04,0.05,0.06,0.07,0.08,0.09,0.10,Adjusted Risk Reduction 25 %, p0.001,Unadjusted Risk Reduction 25 %, p0.001,B. Dahlf at the American College of Cardiology, Atlanta, GA, March 17-20, 2002.,Endpoint Rate,LIFE,2024/8/29,52,New-Onset DiabetesIntention,抗高血压药物：选择原则,心肌梗死：,阻滞剂，,ACEI，ARB？,心绞痛：,阻滞剂，钙拮抗剂,心力衰竭：,ACEI，,利尿剂，,ARB？,老年单纯收缩期高血压：利尿剂，钙拮抗剂（二氢吡啶类）,2024/8/29,53,抗高血压药物：选择原则心肌梗死：阻滞剂，ACEI，ARB？,抗高血压药物：选择原则,房性快速性心律失常：,阻滞剂，钙拮抗剂（非二氢吡啶类）,左心室肥厚：,ACEI，,钙拮抗剂，,阻滞剂，,ARB,血脂异常：,1,阻滞剂,胰岛素抵抗：,ACEI，1,阻滞剂，,ARB？,糖尿病与蛋白尿：,ACEI，,钙拮抗剂，,ARB,2024/8/29,54,抗高血压药物：选择原则房性快速性心律失常：阻滞剂，钙拮抗剂,HOT,：,高血压的理想血压水平,Hansson L, et al.,Lancet.,1998,351:17551762.,90,mm Hg,(144/85),85,mm Hg,(141/83),80,mm Hg,(140/81),138/83,理想血压,The HOT,Study,2024/8/29,55,HOT：高血压的理想血压水平 Hansson L, et a,2024/8/29,56,2023/9/456,2024/8/29,57,2023/9/457,INSIGHT：,需要多少药物控制血压？,Hansson et al. Lancet 1998; 351:1756,2,个及以上药物,(27%),1,个药物,(73%),2024/8/29,58,INSIGHT：需要多少药物控制血压？Hansson et,HOT,：,需要多少药物控制血压？,Hansson et al. Lancet 1998; 351:1756,2个及以上药物,(69%),1个药物,(31%),2024/8/29,59,HOT：需要多少药物控制血压？Hansson et al.,UKPDS：,需要多少药物控制血压？,UKPDS 38. BMJ 1998; 317:703-713,1个药物,(29%),2 个药物,(44%), 3,个以上,(27%),0 或 1,(69%),2 个药物,(23%),Less tight control,Tight control, 3,个以上,(8%),2024/8/29,60,UKPDS：需要多少药物控制血压？UKPDS 38. BMJ,控制血压要用多少种药物?,Source: Bakris,et al,AJKD 2000;36:646-661,1,2,3,4,AASK (92mmHg MAP),HOT (80mmHg -,舒张压),MDRD (92mmHg MAP),ABCD (75mmHg -,舒张压),UKPDS (85mmHg -,舒张压),降压药物数量,在已知的不同血压水平的随机化试验中，为了降低血压而应用的不同类型抗高血压药物的平均数量。,AASK,试验的描述有,Wright,等总结，将在2002年完成,*氨氯地平组在2000年10月停止。,2024/8/29,61,控制血压要用多少种药物?Source: Bakris et,抗高血压药物：单一治疗与联合治疗,Goal BP (140/90),Goal BP (130/85),Change in BP,Dose,First,Second,2024/8/29,62,抗高血压药物：单一治疗与联合治疗Goal BP (140/9,抗高血压药物联合治疗,单一药物治疗只能控制约40%,50%病人的血压达到目标水平，联合治疗可达到80%以上,单一药物治疗只能干预一种血压增高的机制，联合治疗可干预多种机制,减少或抵销药物的不良反应,不同峰效应时间的药物联合有可能延长降压作用时间,增强逆转靶器官损害的效果,2024/8/29,63,抗高血压药物联合治疗单一药物治疗只能控制约40%50%病人,理想的联合用药,作用互补，协同降压,减少副作用,增强对靶器官的有益作用,良好的耐受性,相对低的治疗费用,2024/8/29,64,理想的联合用药作用互补，协同降压2023/9/464,抗高血压药物联合治疗方案,利尿剂,阻滞剂,ACEIs,ARBs,CCBs,+,+,+,+,2024/8/29,65,抗高血压药物联合治疗方案利尿剂阻滞剂ACEIsCCBs+,抗高血压药物联合治疗方案,ACEI,利尿剂,ACEI,钙拮抗剂,钙拮抗剂,受体阻滞剂,阻滞剂利尿剂,2024/8/29,66,抗高血压药物联合治疗方案ACEI利尿剂2023/9/466,不合理的联合治疗方案,阻滞剂 +,Clonidine,阻滞剂 +,ACE,抑制剂,CCBs + ,阻滞剂,非二氢吡啶类,CCBs + ,阻滞剂,CCBs +,利尿剂,2024/8/29,67,不合理的联合治疗方案2023/9/467,2024/8/29,68,2023/9/468,2024/8/29,69,2023/9/469,