絡(luò)活喜胡大一

1、123 以往大量臨床研究表明，降壓治療以往大量臨床研究表明，降壓治療的益處主要來(lái)自血壓降低本身的益處主要來(lái)自血壓降低本身l 臨床試驗(yàn)證實(shí)長(zhǎng)期有效降壓治療能減少臨床試驗(yàn)證實(shí)長(zhǎng)期有效降壓治療能減少30%-50%30%-50% 心腦血管病發(fā)生率。心腦血管病發(fā)生率。l 益處大小受患者心血管危險(xiǎn)程度、血壓控制目標(biāo)益處大小受患者心血管危險(xiǎn)程度、血壓控制目標(biāo) 水平、治療方案降壓以外有利作用或不利作用的水平、治療方案降壓以外有利作用或不利作用的 影響。影響。45高危高血高危高血壓患者壓患者隨機(jī)隨機(jī)氨氯地平氨氯地平氯噻酮氯噻酮多沙唑嗪多沙唑嗪賴諾普利賴諾普利適合降脂治療適合降脂治療不適合降脂治療不適合降脂治療普

2、伐他汀普伐他汀常規(guī)治療常規(guī)治療(Usual Care)隨訪：隨訪： 發(fā)生冠心病發(fā)生冠心病，死亡，或研究結(jié)束死亡，或研究結(jié)束X隨機(jī)隨機(jī)42418 名名670201684123456事件發(fā)生時(shí)間（年）氯噻酮氨氯地平賴諾譜利712氯噻酮氨氯地平賴諾譜利有風(fēng)險(xiǎn)病人數(shù)15 2559048905414 4778576853513 8208218812313 1027843771111 36268246662634038703832295618781770209215195累積事件率（%）氨氯地平氨氯地平vs 氯噻酮氯噻酮: RR 0.98, P=0.65賴諾普利賴諾普利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: 設(shè)計(jì)設(shè)計(jì)選擇性加量至目標(biāo)選擇性加量至目標(biāo) 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氨氯地平組氨氯地平組V 160 mg +HCTZ 25 mg + Free add-onA 10 mg +HCTZ 25 mg + Fre

6、e add-on纈沙坦組纈沙坦組篩選篩選隨機(jī)隨機(jī)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.纈沙坦纈沙坦 (N= 7649)氨氯地平氨氯地平 (N = 7596)135140145150155mmHg月月(或終末隨訪或終末隨訪)治療組隨時(shí)間變化的坐位收縮壓治療組

7、隨時(shí)間變化的坐位收縮壓Baseline12448234612 1830 364254 60 6601.02.03.04.012448mmHg234612 1830 364254 6066月月5.0纈沙坦與氨氯地平纈沙坦與氨氯地平SBP的差異的差異1.0(或終末隨訪或終末隨訪)17Julius S et al. Lancet. June 2004;363.18VALUE:主要終點(diǎn)主要終點(diǎn)(心臟病事件心臟病事件ime (months) 0 612 18 24 30 36 42 48 54 60 66Proportion of Patients With First Eve

8、nt (%)纈沙坦組纈沙坦組氨氯地平組氨氯地平組HR = 1.03; 95% CI = 0.941.14; P = 0.49 Julius S et al. Lancet. June 2004;363.Number at riskValsartanAmlodipine75967649746974597424740772677250711770856772673269556906657665365959591137253765147414746391634919VALUE: 致死性和非致死性腦卒中致死性和非致死性腦卒中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 (%)纈沙坦組纈沙坦組氨氯地平組氨氯地平組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纈沙坦組纈沙坦組氨氯地平組氨氯地平組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/非致死性心臟事件非致死性心臟事件致死致死/非致死性腦卒中非致死性腦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早期降壓有效患者早期降壓有效患者*(n = 9336)非早期降壓有效患者非早期降壓有效患者(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 開(kāi)放的降脂開(kāi)放的降脂治療治療45002250 阿托伐他汀阿托伐他汀2250 安慰劑安慰劑2250 安慰劑安慰劑2250 阿托伐他汀阿托伐他汀4500500 開(kāi)放的降脂開(kāi)放的降脂治療治療8000 開(kāi)放的降脂治療開(kāi)放的降脂治療Sever PS, et al, for the ASCOT investigators. J Hypertens. 2001;19:1139-1147.R = 隨機(jī)的隨機(jī)的上圖為研究計(jì)劃入選的患者數(shù)上圖為研

13、究計(jì)劃入選的患者數(shù)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安慰劑安慰劑1234012320015015075125100100(mg/dL)(mg/dL)總膽固醇總膽固醇 (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隨訪年數(shù)累積事件發(fā)生率（） 阿托伐他汀 10 mg安慰劑p=0.000536% 3.3年年3201230.00.51.01.52.02.53.03.5Years累計(jì)事件發(fā)生率累計(jì)事件發(fā)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事件數(shù)目事件數(shù)目 89安慰劑安慰劑事件數(shù)目事件數(shù)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：降壓提示：降壓+降脂獲益更大降脂獲益更大34新的降壓治療方案新的降壓治療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 傳統(tǒng)降壓治療方案?jìng)鹘y(tǒng)降壓治療方案阿替洛爾阿替洛爾50-100mg 芐氟噻嗪芐氟噻嗪1.25-2.5mg353637ASCOT-BPLA: 事件數(shù)事件數(shù)（2004年年11月月30日）日）主要終點(diǎn)事件主要終點(diǎn)事件869*次要終點(diǎn)事件次要終點(diǎn)事件3192三級(jí)終點(diǎn)事

16、件三級(jí)終點(diǎn)事件2581*具有統(tǒng)計(jì)效力的主要終點(diǎn)事件數(shù)至少應(yīng)有具有統(tǒng)計(jì)效力的主要終點(diǎn)事件數(shù)至少應(yīng)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總冠脈事件終點(diǎn)：總冠脈事件終點(diǎn)：包括非致死性包括非致死性MI/致死性致死性CHD，新發(fā)心絞新發(fā)心絞痛，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/非致死性腦卒中非致死性腦卒中心血管死亡心血管死亡14%10%14%23%16%24%新發(fā)糖尿病新發(fā)糖尿病32%P=0.005P=0.0048P=0.0007P0.0001P=0.0017P值值P0.0001P=0.12

17、* 與試驗(yàn)提前結(jié)束，事件數(shù)未達(dá)到與試驗(yàn)提前結(jié)束，事件數(shù)未達(dá)到1150例有例有關(guān)關(guān)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鈣拮抗劑為主體的治療方案及適應(yīng)癥鈣拮抗劑為主體的治療方案及適應(yīng)癥CCB + 利尿劑 ISHCCB + -阻滯劑 CHD CCB + ARBCHD, AS, 腎臟損害CCB + -阻滯劑 + 利尿劑 重度或急進(jìn)型高血壓CCB + ACEI + 利尿劑 ISH, DMCCB +

22、 ARB ？ + 利尿劑 ISH, DMCCB + -阻滯劑 + ACEI CHD54555657580.050.040.030.020.010.00-0.01P= 0.0070122436內(nèi)膜中層厚度變化內(nèi)膜中層厚度變化(mm)安慰劑安慰劑絡(luò)活喜絡(luò)活喜月月59-60-50-40-30-20-100氨氯地平氨氯地平賴諾普利賴諾普利治療治療14周周治療治療26周周治療治療50周周P=0.044與基線相比與基線相比*P0.05， *P0.001 與與 基基 線線 相相 比比 的的 平平 均均 變變 化化( (nm)nm)*參考文獻(xiàn)：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賴諾普利賴諾普利 520 mg (n=34)6061安慰劑導(dǎo)入安慰劑導(dǎo)入(2-6 周周)清洗清洗:w CCBsw ACEIsw ARBs安慰劑安慰劑(n=1,997)發(fā)病率發(fā)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冠狀動(dòng)脈斑塊冠狀動(dòng)脈斑塊IVUS研究研究安慰劑導(dǎo)入安慰劑導(dǎo)入(2-6 wk)清洗清

24、洗:w CCBsw ACEIsw ARBs安慰劑安慰劑(n=274)氨氯地平氨氯地平 5-10 mg依那普利依那普利 10-20 mgQCAIVUS6364鈣拮抗劑鈣拮抗劑12.1%6.1%5.0%0.001Nissen SF. JAMA 2004;292:221765總體血壓下降均值總體血壓下降均值絡(luò)活喜組絡(luò)活喜組 - 4.8 / 2.5 mm Hg依那普利依那普利組組 - 4.9 / 2.4 mm Hg安慰劑安慰劑組組 + 0.7 / 0.6 mm Hg 絡(luò)活喜組和依那普利組與安慰劑組比較，血壓下降統(tǒng)計(jì)學(xué)差異顯著(P0.001) 絡(luò)活喜組與依那普利組比較，無(wú)顯著性統(tǒng)計(jì)學(xué)差異66心血管累積事

25、件心血管累積事件月月0612182400.250.200.150.100.5安慰劑安慰劑依那普利依那普利絡(luò)活喜絡(luò)活喜No. at risk安慰劑655588558525488依那普利673608572553529絡(luò)活喜66362359957453519%31%15%P=0.16P=0.10P=0.003Nissen SF. JAMA 2004;292:221767他汀方塊大小代表在所有研究人群所占的比例 (例如, 較小的方塊病人數(shù)較少).6825272931333537394143454749安慰劑(n=95) 安慰劑(n=95) 依那普利(n=88) 依那普利(n=88) 絡(luò)活喜(n=91) 絡(luò)活喜(n=91) 基線基線隨訪隨訪P=0.31P=0.001P=0.08粥樣硬化體積百分