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1、BP reduction and CV prevention 降压治疗与心血管病预防 关注降压质量，丰富高血压专业内涵,王继光 上海交通大学医学院附属瑞金医院 上海市高血压研究所,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
2、 1994;50:272-298.,BPLTTC. Lancet 2003;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,Do 5 classes of antihypertensive drugs differ in the prevention
3、 of CV complications ? 5大类降压药物改善结局的作用有差别吗 ?,1. Prevention of stroke CCBs are more protective against stroke. 预防卒中: CCBs 利尿剂/阻滞剂 ACEIs,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/Amlod
4、ipine 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 377/9048 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 2
5、001;37:1305-15. Staessen JA et al. J Hypertens 2003;21:1055-76.,0,ACEIs较好,1,2,3,UKPDS STOP2/ACEIs CAPPP ALLHAT/Lisinopril ANBP2 所有ACEIs p = 0.16,17/358 237/2213 148/5493 675/15255 107/3039 1184/26358,21/400 215/2205 189/5492 457/9054 112/3044 994/20195,10.2% (4.6) 2p = 0.03,ACEIs vs. 利尿剂/阻滞剂: 致死性与非致
6、死性脑卒中,利尿剂/阻滞剂,试验,事件数 / 研究对象人数,异质性检验,危险比 (95%可信区间),差别 (SD),CCBs,利尿剂/阻滞剂较好,Staessen JA, et al. Lancet 2001;37:1305-15. Staessen JA et al. J Hypertens 2003;21:1055-76.,相对危险度 (95% CI),赖诺普利较好,氨氯地平较好,+1% (9% to +11%),CHD,+5% (3% to +13%),总死亡率,+4% (3% to +12%),联合CHD,脑卒中,联合CVD,需要住院的GI出血,心衰,心绞痛,冠脉血运重建,外周动脉疾病
7、,0.5,1.0,2.0,+23% (+8% to +41%),+6% ( 0 to +12%),+20% (+6% to +37%),-13% (22% to 4%),+9% ( 0 to +19%),0 (9% to +11%),+19% (+1% to +40%),P=0.055,P=0.047,P=0.003,P=0.007,P=0.004,P= 0.036,终点事件,差别 (95% CI),Leenen FHH, et al. Hypertension 2006;48:374-384.,ALLHAT：赖诺普利 vs. 氨氯地平,相对危险度 (95% CI),培多普利较好,安慰剂较好,
8、9% (0% to 17%),Combined macro+micro,14% (2% to 25%),All deaths,18% (2% to 32%),CV deaths,Non CV deaths,Total coronary,Total cerebrovascular,Stroke,Heart failure,Total renal events,Total eye events,0.5,1.0,2.0,8% (-12% to 24%),14% (2 to 24%),6% (-10% to 20%),2% (-18% to 19%),21% (15% to 27%),5% (-1%
9、to 10%),P=0.42,终点事件,差别 (95% CI),Patel A et al. Lancet 2007; 370:829-40.,ADVANCE：培多普利 vs. 安慰剂,2% (-20% to 19%),P=0.86,165/1280 102/6108 218/5571,157/1281 98/6110 215/5569,PROGRESS/perindopril only EUROPA ADVANCE,0.5,1,1.5,2.0,培多普利 vs. 安慰剂: 致死性与非致死性脑卒中,培多普利较好,安慰剂较好,安慰剂,试验,事件数 / 研究对象人数,危险比 (95%可信区间),血压
10、差别 (mm Hg),培多普利,5/2 5/2 5.6/2.2,PROGRESS Management Committee. Lancet 200;358:1033-41; Fox K et al. Lancet 2003;362:782-8; Patel A et al. Lancet 2007; 370:829-40.,2. Prevention of MI Amlodipine provides similar protection against MI as ACEIs. 心肌梗死预防: 氨氯地平 利尿剂/阻滞剂 ACEIs,16/1358 154/2213 157/5471 61/3
11、164 1362/15255 17/1157 1767/28618 166/8297 1933/36915,16/1353 179/2196 183/5410 77/3157 798/9048 18/1177 1271/22341 133/8179 1404/30520,4.5% (3.9) 2p = 0.26,1.9% (3.7) 2p = 0.61,MIDAS/NICS/VHAS STOP2/CCBs NORDIL INSIGHT ALLHAT/Amlodipine ELSA CCBs without CONVINCE p = 0.38 CONVINCE All CCBs p = 0.14
12、,0,1,2,3,CCBs vs. 利尿剂/阻滞剂: 致死性与非致死性心肌梗死,CCBs较好,利尿剂/阻滞剂较好,利尿剂/阻滞剂,试验,事件数 / 研究对象人数,异质性检验,危险比 (95%可信区间),差别 (SD),CCBs,Staessen JA, et al. Lancet 2001;37:1305-15. Staessen JA et al. J Hypertens 2003;21:1055-76.,0.20 0.15 0.10 0.05 0.00,0 1 2 3 4 5 6 7,基线CHD,随访时间（年）,赖/氨 1.06(0.99-1.32) 0.69,RR(95%Cl) P 值,
13、0.20 0.15 0.10 0.05 0.00,0 1 2 3 4 5 6 7,基线无CHD,氨氯地平 赖诺普利,赖/氨 0.98(0.88-1.13) 0.78,RR(95%Cl) P 值,ALLHAT: 致死/非致死性CHD发生率,随访时间（年）,Leenen FHH, et al. Hypertension 2006;48:374-384.,CHD累计发生率,AHA/ACC高血压合并冠心病降压治疗建议： 各类降压药物的异质性,Rosendorff C et al. Circulation 2007;115:2761-88.,There is also continuing debate
14、 over whether there are “class effects” for antihypertensive drugs or whether each drug must be considered individually. It is reasonable to assume that there are class effects for thiazide-type diuretics, ACE inhibitors, and ARBs, which have a high degree of homogeneity in their mechanisms of actio
15、n and side effects. It is equally clear that there are major differences between drugs within more heterogeneous classes of agents, such as -blockers or CCBs.,3. Prvention of stroke and MI Amlodipine vs. ARBs 脑卒中与心肌梗死预防: 氨氯地平 vs. ARBs,Prevention of stroke and MI by amlodipine and ARBs 氨氯地平与ARBs预防卒中与
16、心肌梗死 A meta-analysis of RCTs 随机对照临床试验综合分析,Wang JG et al. Hypertension 2007; 50: 333-339.,氨氯地平 vs. ARBs*: 脑卒中,氨氯地平较好,ARBs较好,IDNT VALUE CASE-J 所有试验 p = 0.46,30/579 322/7649 60/2354 412/10,582,18/567 281/7596 47/2349 346/10,512,15.9% (6.2) 2p = 0.02,0.5,1.0,1.5,2.0,* 厄贝沙坦、缬沙坦、坎地沙坦,ARBs,氨氯地平,试验,事件数 / 研究
17、对象人数,异质性检验,危险比 (95%可信区间),差别 (SD),Wang JG et al. Hypertension 2007; 50:333-339.,IDNT VALUE CASE-J All trials p = 0.40,51/579 369/7649 17/2354 437/10,582,33/567 281/7596 18/2349 332/10,512,16.7% (6.1) 2p = 0.01,0.5,1.0,1.5,2.0,氨氯地平 vs. ARBs*: MI,ARBs,试验,事件数 / 研究对象人数,异质性检验,危险比 (95%可信区间),差别 (SD),氨氯地平,氨氯
18、地平较好,ARBs较好,* 厄贝沙坦、缬沙坦、坎地沙坦,Wang JG et al. Hypertension 2007; 50:333-339.,Why differ, beyond BP control, or because of better BP control ? 为什么有差别，是“降压外作用”，还是“高质量的降压才是硬道理”？,1. Lower systemic BP Central vs. peripheral BP 降低整个动脉系统的血压: 中心动脉压 vs. 肱动脉血压,不同部位的血压水平有所不同,CAFE研究：外周与中心血压,外周SBP: mean =0.7 (-0.4
19、to 1.7) mm Hg,中心SBP: mean =4.3 (3.3 to 5.4) mm Hg,133.9 133.2 125.5 121.2,SBP (mm Hg),Time since randomisation (years),Williams B, et al. Circulation 2006;113:1213-1225.,阿替洛尔 氨氯地平,2. Lower 24-hour BP The role of morning surge 降低24小时血压: 晨峰血压,Pedersen et al. J Hypertens 2007;25:707-712.,Mean SBP diffe
20、rence (Amlodipine-valsartan, mm Hg),1,6,11,16,21,-4,-3,-1,0,1,2,给药后时间（小时）,-2,ABPM in VALUE: 给药后24小时内收缩压的差别(氨氯地平 vs 缬沙坦，n=659),-2.7mmHg P=0.039,Pedersen et al. J Hypertens 2007;25:707-712.,Early morning BP surge,清晨高血压的风险,6:00,0:00,12:00,18:00,Muller et al. N Engl J Med 1985;313:13151322; Marler et al
21、. Stroke 1989;20:473476.,0,20,40,60,80,100,120,140,160,180,卒中 (per 2 h),0,5,10,15,20,25,30,35,40,45,50,心肌梗死 (per h),Stroke (n=1,167),Myocardial infarction (n=2,999),Time of the day,3. Not too low, not too fast Treat patients individually 不宜太低，不应太快: 应遵循个体化原则,MI或卒中发病率(%),MI Stroke,60,60 to 70,70 to 80
22、,80 to 90,90 to 100,100 to 110,110,0,5,10,15,20,25,30,35,随访期间的平均舒张压 (mm Hg),MI and stroke by average follow-up DBP in INVEST,Messerli FH et al. Ann Intern Med 2006;144:88493.,高血压合并冠心病患者降压治疗,130/80,缺血性心脏病心衰,130/80,STEMI,不稳定性心绞痛或NSTEMI,130/80 or 120/80,稳定性心绞痛,not 60 mm Hg,slowly,130/80,合并冠心病危险因素,特别注意,
23、降压速度,降压治疗目标血压(mm Hg),冠心病不同阶段,Rosendorff C et al. Circulation 2007;115:2761-88.,not 60 mm Hg,not 60 mm Hg,not 60 mm Hg,not 60 mm Hg,slowly,slowly,slowly,slowly,130/80 or 120/80,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关键。 与利尿剂、阻滞剂、ACEIs以及ARBs相比，CCBs具有较强的脑卒中预防作用。卒中是我国高血压患者最常见的并发症，因此，CCBs应作为我国高血压患者的基础性用药。 各种DHP-CCBs之间预防心肌梗死的作用可能存在很大差异。氨氯地平是唯一有证据显示与利尿剂、阻滞剂、ACEIs具有相似的预防心肌梗死作用的DHP-CCB。 降压药物之间的差异很可能仅仅是其降压质量的差异。与其强调降压之外的作用，不如强化降压、降脂、降糖等多重危险因素干预。,Thank you very much ！,