络活喜胡大一

1、123 以往大量临床研究表明，降压治疗以往大量临床研究表明，降压治疗的益处主要来自血压降低本身的益处主要来自血压降低本身l 临床试验证实长期有效降压治疗能减少临床试验证实长期有效降压治疗能减少30%-50%30%-50% 心脑血管病发生率。心脑血管病发生率。l 益处大小受患者心血管危险程度、血压控制目标益处大小受患者心血管危险程度、血压控制目标 水平、治疗方案降压以外有利作用或不利作用的水平、治疗方案降压以外有利作用或不利作用的 影响。影响。45高危高血高危高血压患者压患者随机随机氨氯地平氨氯地平氯噻酮氯噻酮多沙唑嗪多沙唑嗪赖诺普利赖诺普利适合降脂治疗适合降脂治疗不适合降脂治疗不适合降脂治疗普

2、伐他汀普伐他汀常规治疗常规治疗(Usual Care)随访：随访： 发生冠心病发生冠心病，死亡，或研究结束死亡，或研究结束X随机随机42418 名名670201684123456事件发生时间（年）氯噻酮氨氯地平赖诺谱利712氯噻酮氨氯地平赖诺谱利有风险病人数15 2559048905414 4778576853513 8208218812313 1027843771111 36268246662634038703832295618781770209215195累积事件率（%）氨氯地平氨氯地平vs 氯噻酮氯噻酮: RR 0.98, P=0.65赖诺普利赖诺普利vs 氯噻酮氯噻酮: RR 0.99

3、, P=0.8189InstituteforInternationalHealth10AASKABCD (H)ABCD (N) ALLHATANBP2CAPPPCONVINCEELSAHOPE HOTIDNTINSIGHTJMIC-BLIFENICOLENICS-EHNORDILPART-2PREVENTPROGRESSQUIETRENAALSCATSCOPESHELLSTOP-2SYST-EURUKPDS-HDSVHAS1112 RR (95% CI) Favours first listed Favours second listedBP difference(mm Hg)0.51.02.

4、0Relative Risk 0.96 (0.88,1.05) 1.01 (0.94,1.08) 0.98 (0.91,1.05) ACE vs. CA CA vs. D/BB ACE vs. D/BB2/01/01/113 RR (95% CI) Favours first listed Favours second listed0.51.02.0Relative RiskBP difference(mm Hg) 1.09 (1.00,1.18) ACE vs. D/BB 0.93 (0.86,1.01) CA vs. D/BB 1.12 (1.01,1.25) ACE vs. CA2/01

5、/01/114HTNCADCHD/CADHTNCHDHTN* CCB=苯磺酸氨氯地平苯磺酸氨氯地平*15VALUE: 设计设计选择性加量至目标选择性加量至目标 BP (140/90 mmHg)Month0.5 0 1 2 3 4 6 * 72A 10 mg +HCTZ 25 mgA 5 mgA 10 mg +HCTZ 12.5 mgA 10 mgV 80 mgV 160 mgV 160 mg +HCTZ 12.5 mgV 160 mg +HCTZ 25 mg氨氯地平组氨氯地平组V 160 mg +HCTZ 25 mg + Free add-onA 10 mg +HCTZ 25 mg + Fre

6、e add-on缬沙坦组缬沙坦组筛选筛选随机随机End of treatment adjustment periodRolloverfromprevious therapy(92%)*Patient visits every 6 months for months 672.Julius S et al. Lancet. June 2004;363.16Julius S et al. Lancet. June 2004;363.缬沙坦缬沙坦 (N= 7649)氨氯地平氨氯地平 (N = 7596)135140145150155mmHg月月(或终末随访或终末随访)治疗组随时间变化的坐位收缩压治疗组

7、随时间变化的坐位收缩压Baseline12448234612 1830 364254 60 6601.02.03.04.012448mmHg234612 1830 364254 6066月月5.0缬沙坦与氨氯地平缬沙坦与氨氯地平SBP的差异的差异1.0(或终末随访或终末随访)17Julius S et al. Lancet. June 2004;363.18VALUE:主要终点主要终点(心脏病事件心脏病事件ime (months) 0 612 18 24 30 36 42 48 54 60 66Proportion of Patients With First Eve

8、nt (%)缬沙坦组缬沙坦组氨氯地平组氨氯地平组HR = 1.03; 95% CI = 0.941.14; P = 0.49 Julius S et al. Lancet. June 2004;363.Number at riskValsartanAmlodipine75967649746974597424740772677250711770856772673269556906657665365959591137253765147414746391634919VALUE: 致死性和非致死性脑卒中致死性和非致死性脑卒中Julius S et al. Lancet. June 2004;363.N

9、umber at riskValsartanAmlodipine7596764974997494745574487334731271957170691868777055702267446692616360933846385915321516658765156543210Time (months)0612 18 24 30 36 42 48 54 60 66Proportion of Patients With First Event (%)缬沙坦组缬沙坦组氨氯地平组氨氯地平组HR = 1.15; 95% CI = 0.981.35; P = 0.08 20Time (months)Number

10、 at riskValsartanAmlodipine759676497497749974587458733273197205717769056853706570166727668061416078384038641532152065626504Proportion of Patients With First Event (%)76543210VALUE: 致死及非致死心肌梗死致死及非致死心肌梗死0612 18 24 30 36 42 48 54 60 66缬沙坦组缬沙坦组氨氯地平组氨氯地平组HR = 1.19; 95% CI = 1.02-1.38; P = 0.02 Julius S e

11、t al. Lancet. June 2004;363.1921致死致死/非致死性心脏事件非致死性心脏事件致死致死/非致死性脑卒中非致死性脑卒中全因死亡全因死亡心肌梗死心肌梗死心衰住院心衰住院0.40.60.81.01.21.4早期降压有效患者早期降压有效患者*(n = 9336)非早期降压有效患者非早期降压有效患者(n = 5663)Odds Ratio 95% CI*Those not on previous tx: SBP 10 mmHg at one month; those on previous tx: SBP baseline at one month.*P 0.05; P 6.

12、5 mmol/L (250 mg/dL)4000 TC 6.5 mmol/L (250 mg/dL)5000 TC 6.5 mmol/L ( 250 mg/dL)500 开放的降脂开放的降脂治疗治疗45002250 阿托伐他汀阿托伐他汀2250 安慰剂安慰剂2250 安慰剂安慰剂2250 阿托伐他汀阿托伐他汀4500500 开放的降脂开放的降脂治疗治疗8000 开放的降脂治疗开放的降脂治疗Sever PS, et al, for the ASCOT investigators. J Hypertens. 2001;19:1139-1147.R = 随机的随机的上图为研究计划入选的患者数上图为研

13、究计划入选的患者数28Sever PS, et al, for the ASCOT investigators. J Hypertens. 2001;19:1139-1147.29302460123阿托伐他汀阿托伐他汀 10 mg安慰剂安慰剂1234012320015015075125100100(mg/dL)(mg/dL)总胆固醇总胆固醇 (mmol/L)LDL -C (mmol/L)Years1.3 mmol/L1.0 mmol/L1.2 mmol/L1.0 mmol/LSever PS, Dahlf B, Poulter N, Wedel H, et al, for the ASCOT

14、Investigators. Lancet. 2003;361:1149-58Close-out31012340.00.51.01.52.02.53.03.5随访年数累积事件发生率（） 阿托伐他汀 10 mg安慰剂p=0.000536% 3.3年年3201230.00.51.01.52.02.53.03.5Years累计事件发生率累计事件发生率 (%)27%HR = 0.73 (0.56-0.96)p=0.0236阿托伐他汀阿托伐他汀 10 mg事件数目事件数目 89安慰剂安慰剂事件数目事件数目121Sever PS, Dahlf B, Poulter N, Wedel H, et al, f

15、or the ASCOT Investigators. Lancet. 2003;361:1149-5833Sever PS, et al, Lancet. 2003;361:1149-58提示：降压提示：降压+降脂获益更大降脂获益更大34新的降压治疗方案新的降压治疗方案苯磺酸氨氯地平苯磺酸氨氯地平5-10mg 培哚普利培哚普利4-8mg 传统降压治疗方案传统降压治疗方案阿替洛尔阿替洛尔50-100mg 苄氟噻嗪苄氟噻嗪1.25-2.5mg353637ASCOT-BPLA: 事件数事件数（2004年年11月月30日）日）主要终点事件主要终点事件869*次要终点事件次要终点事件3192三级终点事

16、件三级终点事件2581*具有统计效力的主要终点事件数至少应有具有统计效力的主要终点事件数至少应有1150例例383940414243全因死亡全因死亡非致死性非致死性MI / 致死性致死性CHD总冠脉事件终点：总冠脉事件终点：包括非致死性包括非致死性MI/致死性致死性CHD，新发心绞新发心绞痛，致死痛，致死/非致死性心衰非致死性心衰所有心血管事件和操作所有心血管事件和操作致死致死/非致死性脑卒中非致死性脑卒中心血管死亡心血管死亡14%10%14%23%16%24%新发糖尿病新发糖尿病32%P=0.005P=0.0048P=0.0007P0.0001P=0.0017P值值P0.0001P=0.12

17、* 与试验提前结束，事件数未达到与试验提前结束，事件数未达到1150例有例有关关4445Arterial wall compliance, percent change from baseline to week 8 (667 patients with hypertension and high LDL)Size of artery Combination Amlodipine Atorvastatin Placebo Large (%) 10.2*10.1*-1.73.3Small (%) 19.6*11.6*2.2-2.1*p0.0001 vs baseline. *p=0.0002 v

18、s baseline. *p=0.0011 vs baseline.46Blood-pressure control was better early on with amlodipine/perindopril. Although levels were virtually identical by the end of the trial, the mean difference was 2.9/1.8 mm Hg through the course of the study. Dr Bjrn Dahf (Sahlgrenska University Hospital, Oslo, No

19、rway) 47the ASCOT results reinforce an earlier lesson from the VALUE study, that in complex patients such as those in ASCOT, a calcium antagonist should be part of the antihypertensive cocktail. In VALUE, as in ASCOT, blood-pressure control was achieved more promptly with amlodipine. Dr Franz H Mess

20、erli (St Lukes-Roosevelt Hospital, New York, NY)48A calcium antagonist, together with an ACE inhibitor if needed, allows for better blood-pressure control, fewer side effects such as new-onset diabetes, less add-on medication for better persistence with antihypertensive therapy, and last but not lea

21、st, a greater reduction in morbidity and mortality than with beta blockers and diuretics. Dr Franz H Messerli (St Lukes-Roosevelt Hospital, New York, NY)4950515253钙拮抗剂为主体的治疗方案及适应症钙拮抗剂为主体的治疗方案及适应症CCB + 利尿剂 ISHCCB + -阻滞剂 CHD CCB + ARBCHD, AS, 肾脏损害CCB + -阻滞剂 + 利尿剂 重度或急进型高血压CCB + ACEI + 利尿剂 ISH, DMCCB +

22、 ARB ？ + 利尿剂 ISH, DMCCB + -阻滞剂 + ACEI CHD54555657580.050.040.030.020.010.00-0.01P= 0.0070122436内膜中层厚度变化内膜中层厚度变化(mm)安慰剂安慰剂络活喜络活喜月月59-60-50-40-30-20-100氨氯地平氨氯地平赖诺普利赖诺普利治疗治疗14周周治疗治疗26周周治疗治疗50周周P=0.044与基线相比与基线相比*P0.05， *P0.001 与与 基基 线线 相相 比比 的的 平平 均均 变变 化化( (nm)nm)*参考文献：Stanton AV et al. J Hypertens. 19

23、98;16(suppl 2):S25.v氨氯地平氨氯地平 510 mg (n=34)v赖诺普利赖诺普利 520 mg (n=34)6061安慰剂导入安慰剂导入(2-6 周周)清洗清洗:w CCBsw ACEIsw ARBs安慰剂安慰剂(n=1,997)发病率发病率/死亡率研究死亡率研究氨氯地平氨氯地平 5-10 mg依那普利依那普利 10-20 mgNissen SE, et al, for the CAMELOT investigators. JAMA. 2004;292:2217-2226.62QCAIVUS冠状动脉斑块冠状动脉斑块IVUS研究研究安慰剂导入安慰剂导入(2-6 wk)清洗清

24、洗:w CCBsw ACEIsw ARBs安慰剂安慰剂(n=274)氨氯地平氨氯地平 5-10 mg依那普利依那普利 10-20 mgQCAIVUS6364钙拮抗剂钙拮抗剂12.1%6.1%5.0%0.001Nissen SF. JAMA 2004;292:221765总体血压下降均值总体血压下降均值络活喜组络活喜组 - 4.8 / 2.5 mm Hg依那普利依那普利组组 - 4.9 / 2.4 mm Hg安慰剂安慰剂组组 + 0.7 / 0.6 mm Hg 络活喜组和依那普利组与安慰剂组比较，血压下降统计学差异显著(P0.001) 络活喜组与依那普利组比较，无显著性统计学差异66心血管累积事

25、件心血管累积事件月月0612182400.250.200.150.100.5安慰剂安慰剂依那普利依那普利络活喜络活喜No. at risk安慰剂655588558525488依那普利673608572553529络活喜66362359957453519%31%15%P=0.16P=0.10P=0.003Nissen SF. JAMA 2004;292:221767他汀方块大小代表在所有研究人群所占的比例 (例如, 较小的方块病人数较少).6825272931333537394143454749安慰剂(n=95) 安慰剂(n=95) 依那普利(n=88) 依那普利(n=88) 络活喜(n=91) 络活喜(n=91) 基线基线随访随访P=0.31P=0.001P=0.08粥样硬化体积百分