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1、高血压的药物治疗 种族因素,上海交通大学医学院附属瑞金医院 上海市高血压研究所 王继光 2008年3月8日，北京,Relative risk reductions by antihypertensive treatment in early trials,Progression to severe HT,CHF,Stroke,CHD,Total mortality,CV mortality,-94*,-53%*,-40%*,-16%*,-13%,-21%*,*P0.05,Collins R et al. Br Med Bull 1994;50:272-298.,BPLTTC. Lancet 2
2、003;362:1527-45.,0 -5 -10 -15 -20 -25 -30,Stroke,CHD,CHF,Total mortality,-23%,-15%,-16%,-14%,4/3 mmHg,N20 888,Major CV events,-15%,Relative risk reductions by antihypertensive treatment in recent trials,HOT study Hypertension Optimal Treatment trial 80 vs 85 vs 90 mm Hg Lancet 1998;351:1755-1762.,HO
3、T: Antihypertensive drug treatment,Step 1 5 mg felodipine Step 2 5 mg felodipine + low dose ACE inhibitor or b-blocker Step 3 10 mg felodipine + low dose ACE inhibitor or b-blocker Step 4 10 mg felodipine + high dose ACE inhibitor or b-blocker Step 5 10 mg felodipine + high dose ACE inhibitor or b-b
4、locker + low dose alternative addition or HCTZ,Hansson L et al. Lancet 1998;351:1755-1762.,Mean DBP measured from 6 months and onwards,0,5,10,15,20,25,Target 80 : 81.1 (5.3),Target 85 : 83.2 (4.8),Target 90 : 85.2 (5.1),Frequency %,60,Achieved DBP, mm Hg,70,80,90,100,110,Hansson L et al. Lancet 1998
5、;351:1755-1762.,Target 80 : 139.7 (11.7),Mean SBP measured from 6 months and onwards,100,0,5,10,15,20,25,Frequency %,110,120,130,140,150,160,170,180,190,Target 85 : 141.4 (11.7),Target 90 : 143.7 (11.3),Achieved SBP, mm Hg,Hansson L et al. Lancet 1998;351:1755-1762.,Major CV events in relation to ta
6、rget BP groups, 90 232 9.9 90 vs. 85 0.99 (0.83 - 1.19) 85 234 10.0 85 vs. 80 1.08 (0.89 - 1.29) 80 217 9.3 0.50 90 vs. 80 1.07 (0.89 - 1.28),Events No. of Events/1000 P-value Comparison Risk (95%CI) events p-yrs trend,Hansson L et al. Lancet 1998;351:1755-1762.,n=18,790,Major CV events/ 1000 p-yrs,
7、Target DBP mm Hg,n=1501 p=0.005 for trend, 90, 85, 80,Major CV events in patients with DM at Rx in relation to target BP groups,HYVET Hypertension in the Very Elderly Trial Indapamide vs. placebo Drugs Aging 2001;18:151-64.,收缩压差别 10 mm Hg 脑卒中 (no. events100) 40% 总死亡率 (no. events300) 15%,Personal com
8、munications,HYVET 2007-7,Any diabetes related endpoint,Number of endpoints 1401 of 3867 patients (36%),0%,20%,40%,60%,0,3,6,9,12,15,% of patients with an event,Years from randomisation,Intensive (n=2729),Conventional (n=1138),Risk reduction 12% (95% CI: 1% to 21%) p=0.029,UKPDS 33. Lancet 1998;352:8
9、37-53,Risk reduction 24% p=0.0046,Any diabetes related endpoint,% of patients with events,0%,10%,20%,30%,40%,50%,0,3,6,9,Years from randomisation,Tight BP control (n=758),Less tight BP control (n=390),UKPDS 38. BMJ 1998; 317:703-713,Prevention of cardiovascular events in diabetic patients,Action in
10、Diabetes and Vascular disease: preterAx and diamicroN MR Controlled Evaluation,ADVANCE: 主要终点 Major macro or microvascular event,0,10,20,Follow-up (months),0,6,12,18,24,30,36,42,48,54,60,Placebo,Perindopril-Indapamide,Relative risk reduction 9%: 95% CI: 0 to 17% p=0.041,Cumulative incidence (%),Patel
11、 A et al. Lancet 2007; 370:829-40.,指南推荐,利尿剂 阻滞剂 钙离子拮抗剂 转换酶抑制剂 血管紧张素受体拮抗剂,J Hypertens 2007;25:1105-87.,到底该如何选择降压药物 ?,特别注意,应该坚持使用指南推荐使用的降压药物。 5大类药物均可作为起始治疗药物使用，并不意味着可以不加选择地使用药物，当然也不是每类药物都应该有同等即20%机会作为一线药物使用。 应该根据临床试验的证据原则、降压作用与副作用，选择对患者最为合适的药物。,CCBs vs. 利尿剂/阻滞剂: 致死性与非致死性脑卒中,利尿剂/阻滞剂,CCBs,试验,事件数 / 研究对象人
12、数,异质性检验,危险比 (95%可信区间),差别 (SD),0,CCBs较好,1,2,3,利尿剂/阻滞剂较好,MIDAS/NICS/VHAS STOP2/CCBs NORDIL INSIGHT ALLHAT/Amlodipine ELSA CCBs without CONVINCE p = 0.68 CONVINCE 所有CCBs p = 0.39,15/1358 237/2213 196/5471 74/3164 675/15255 14/1157 1211/28618 118/8297 1329/36915,19/1353 207/2196 159/5410 67/3157 377/904
13、8 9/1177 838/22341 133/8179 971/30520,10.2% (4.8) 2p = 0.02,7.6% (4.4) 2p = 0.07,Staessen JA, et al. Lancet 2001;37:1305-15. Staessen JA et al. J Hypertens 2003;21:1055-76.,Possible combinations of antihypertensive drugs,J Hypertens 2007;25:1105-87.,Thiazide diuretics,ACEIs,ARBs,CCBs,-blockers,-bloc
14、kers,The BHS-NICE guideline,www.nice.org.uk,55 years,55 years or black patients of any age,A,C or D,Step 1,A+C or A+D,Step 2,Step 3,A+C+D,Step 4,Add: further diuretic therapy, -blocker, -blocker Consider seeking specialist advice,Systemic rotation ABCD or AB/CD rule,CD,Dickerson JEC et al. Lancet 19
15、99; 353: 2008-2013.,BP by treatment group and ethnicity,Wright JT et al. JAMA 2005:293:1595-1608.,ALLHAT: % on 3+ antihypertensive drugs by randomized group and ethnicity at 5 y,Wright JT et al. JAMA 2005:293:1595-1608.,ALLHAT: BP control (140/90 mm Hg) by randomized group and ethnicity at 5 y,135/7
16、8,136/76,139/79,133/74,134/74,134/74,Wright JT et al. JAMA 2005:293:1595-1608.,不同种族患者对降压药物的反应,Khan JM et al. Heart. 2005;91;1105-1109.,HOT：舒张压下降,HOT：收缩压下降,亚洲病人 其他病人,0 -5 -10 -15 -20 -25 -30 -35 -40,90,85,80,收缩压 mm Hg,mm Hg,p0.0001,p0.01,p0.0001,目标舒张压,HOT: 不良反应,发生副作用的病人 (%),随访时间,其他病人,亚洲病人,FEVER 非洛地平降
17、低心脑血管事件的研究 J Hypertens 2005;23:2157-2172.,+ 非洛地平 5 mg/d,+ 安慰剂,HCTZ 12.5 mg/d,随访 周,1 -6,2 -4,3 -2,4 0,5 1,6 2,7 3,8 4,9 5,10 6,11 9,12 12,16 24,20 36,24 48,28 60,月,筛选,随机化,加用利尿剂或者其它降压药物 (除外CCB) , 如果BP 160/90 mmHg,FEVER：研究流程,Liu LS et al. J Hypertens 2005;23:2157-2172.,-6,0,6,12,18,24,30,36,42,48,54,60
18、,120,130,140,150,160,170,SBP (mmHg),随访 (月),142.5,137.3,141.6,138.1,安慰剂 非洛地平,S,R,平均差异 4mmHg,FEVER：收缩压 非洛地平+HCTZ vs HCTZ,Liu LS et al. J Hypertens 2005;23:2157-2172.,75,80,85,90,95,100,DBP (mmHg),随访 (月),85.0,82.5,83.9,82.3,安慰剂 非洛地平,平均差异 2mmHg,-6,0,6,12,18,24,30,36,42,48,54,60,S,R,FEVER：舒张压 非洛地平+HCTZ v
19、s HCTZ,Liu LS et al. J Hypertens 2005;23:2157-2172.,0,2,4,6,8,10,0,6,12,18,24,30,36,42,48,54,60,26.8%,FEVER： 主要终点事件,HCTZ 非洛地平+HCTZ,随访时间（月）,主要终点（%）,Liu LS et al. J Hypertens 2005;23:2157-2172.,FEVER： 终点事件,Liu LS et al. J Hypertens 2005;23:2157-2172.,降压治疗是最有效的心血管药物治疗手段，因此，高血压一旦确诊，应及早开始降压治疗。 降低血压是抗高血压治疗获益的根本原因。在密切注意降压治疗的安全的情况下，应尽可能把血压控制得更低些。 目前指南推荐使用5大类降压药物。但不同药物，不仅对某些并发症，或某些患者，降低并发症的获益会有所不同，而且其降压作用在不同种族间也存在一定差异。总体而言，DHP-CCBs和利尿剂可能对东亚和非洲人降压作用更强，而ACEIs以及ARBs、 阻滞剂则可能对白种人的降压作用更强些。 选择合适的起始治疗药物、合理的联合降压治疗方案，配合积极的多重危险因素干预，最终大幅度地降低心脑血管并发症风险。,Thank you very much ！,