络活喜相关大型临床研究解读

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,112,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,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,单击此处编辑母版标题样式,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,2024/9/27,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,*,*,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,单击此处编辑母版标题样式,*,*,仅供内部使用,络活喜相关大型临床研究解读,沧海横流 方显英雄本色！,1990,1993,1996,1994,2000,2004,2002,2003,2005,络活喜,（苯磺酸氨氯地平）,问世,TOMHS,：,络活喜显著降低轻中度高血压患者血压，具有良好的安全性和耐受性,CAPE,：,络活喜显著降低慢性稳定性心绞痛患者有症状和无症状心肌缺血发作，作用可维持,24,小时以上,PRAISE,：,络活喜能安全用于伴重度心衰的高血压患者,PREVENT,：,络活喜显著减缓,CAD,患者颈动脉,IMT,进展，降低冠脉心血管事件,ALLHAT,：,络活喜在广泛的高血压患者群有一致的降压效果和心血管获益；络活喜安全性得到最可靠的证实,IDNT,：,络活喜明显降低,2,型糖尿病肾病患者心肌梗死的发生率,VALUE,：,络活喜降压作用优于新型,ARB,缬沙坦，并可显著减少心肌梗死发生率,CAMELOT/NORMALISE,：,络活喜对稳定,CAD,的患者能进一步显著减少心血管事件，,IVUS,直观证实可减缓冠状动脉粥样硬化进展,ASCOT,：,以络活喜为基础的新型降压联合用药方案显著优于以,阻滞剂为基础的传统降压联合用药方案,近年来,CCB,的大型研究,均以络活喜的研究为主,2002,ALLHAT,2003INVEST,2004,VALUE,2004,CAMELOT,2004ACTION,2005FEVER,2005,ASCOT,2006,ASCOT-CAF,2006ALLHAT,CCB vs ACEI,亚组,VALUE,研究,:,络活喜,利尿剂,欧洲最大的高血压研究,: ASCOT,研究,:,络活喜,ACEI,世界最大的高血压研究,ALLHAT,研究,:,络活喜,B,阻滞剂,/,其他药物,络活喜众多大型循证研究奠定了,CCB,基础用药的地位,均以络活喜为基础用药,!,抗高血压和降脂治疗预防心肌梗死的试验,比较高危高血压患者服用,ACEI(,赖诺普利,), CCB(,络活喜,),-,阻滞剂,(,多沙唑嗪,),与传统的利尿剂,(,氯噻酮,),治疗减少,致死性冠心病和非致死性心肌梗死,的差异,ALLHAT,研究的目的,Davis BR, Culter JA, Gordon DJ, et al, for the ALLHAT Research Group. Rationale and design for the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial(ALLHAT). AJH. 1996; 9: 342-360.,ALLHAT,试验设计,高危高血,压患者,随机,氨氯地平,氯噻酮,多沙唑嗪,赖诺普利,适合降脂治疗,不适合降脂治疗,普伐他汀,常规治疗(,Usual Care),随访： 发生冠心病,，,死亡，或研究结束,X,随机,42418 名,42,418,名患者,平均年龄,67,岁,(35%70,岁,),47%,女性,36%,黑人,36%,伴有糖尿病,47%,已知心血管疾病,ALLHAT,广泛的患者群,Grimm RH Jr, Margolis KL, Papademetriou V, et al, for the ALLHAT Collaborative Research Group. Baseline characteristics of participants in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertension. 2001; 37: 19-27.,血压控制,The ALLHAT Officers and Coordinators for the ALLHAT,Collaborative research Group. JAMA, 2002; 288: 2981-2997.,0,20,16,8,4,1,2,3,4,5,6,事件发生时间（年）,氯噻酮,氨氯地平,赖诺谱利,ALLHAT：,各治疗组主要终点（致死性冠心病和非致死性心肌梗死）无显著差异,7,12,氯噻酮,氨氯地平,赖诺谱利,有风险病人数,15 255,9048,9054,14 477,8576,8535,13 820,8218,8123,13 102,7843,7711,11 362,6824,6662,6340,3870,3832,2956,1878,1770,209,215,195,累,积,事件率（%）,氨氯地平,vs,氯噻酮:,RR 0.98, P=0.65,赖诺普利,vs,氯噻酮:,RR 0.99, P=0.81,络活喜,与利尿剂组在心血管次要终点上均无差异；,而赖诺普利与利尿剂组相比，脑卒中增加,15%,，心,血管疾病总和增加,10%,The ALLHAT Officers and Coordinators for the ALLHAT Collaborative research Group. JAMA, 2002; 288: 2981-2997.,络活喜,防治脑卒中的理想选择,1,1. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative research Group. JAMA, 2002; 288: 2981-2997.,2. An Expert Interview With Frans H. Leenen, MD, PhD.,Medscape Cardiology 7(1), 2003.,ALLHAT,的意义,有效的血压控制是心，脑血管事件降低的根本,络活喜,在广泛的患者群（老年人，不同种族，糖尿病患者）降低所有主要和次要终点的结果一致,络活喜,降低冠心病事件和公认有益的,ACEI,一致,降低卒中更优,络活喜,的安全性得到了最可靠的证实（不增加肿瘤，消化道出血和终末期肾病的风险）,ALLHAT Collaborative Research Group.,JAMA,. 2002;288:2981-2997.,ALLHAT,表明,降压是抗高血压药物减少心血管事件的根本！,2006,年,ALLHAT,亚组分析进一步证实了专家关于预防卒中的评论！,ALLHAT,亚组分析：氨氯地平,vs. ACEI,研究进程,1994,年,2002,年,2006,年,研究开始,发表结果（,JAMA,）,氨氯地平,vs.,氯噻酮,赖诺普利,vs.,氯噻酮,发表结果（,Hypertension,）,氨氯地平,vs.,赖诺普利,Frans H.H. Leenen et al. Hypertension. 2006;48:374-384.,HYPERTENSION2006,年,9,月,最新发表,ALLHAT,亚组分析,将氨氯地平与,ACEI,直接对比,0.20,0.15,0.10,0.05,0.00,0 1 2 3 4 5 6 7,基线,CHD,氨氯地平,赖诺普利,一级终点事件发生时间（年）,赖,/,氨,1.06(0.99-1.32) 0.69,RR(95%Cl),P,值,累计,CHD,发生率,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,2006ALLHAT,亚组：,络活喜与赖诺普利预防,致死,/,非致死性冠心病疗效相同,ALLHAT,一级终点事件发生时间（年）,Frans H.H. Leenen et al. Hypertension. 2006;48:374-384.,2006 ALLHAT,亚组： 氨氯地平总体优于赖诺普利,RR (95% CI),Favours Lisinopril,Favours,Amlodipine,1.01 (0.91,1.11),CHD,1.05 (0.97,1.13),全因死亡,1.04 (0.97,1.12),联合,CHD,脑卒中,联合,CVD,ESRD,癌症,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,0.5,1.0,2.0,1.23 (1.08,1.41),1.06 (1.00,1.12),0.99 (0.77,1.26),1.01 (0.91,1.12),1.20 (1.06,1.37),0.87 (0.78,0.96),1.09 (1.00,1.19),1.00 (0.91,1.11),1.19 (1.01,1.40),P=0.045,P=0.047,P=0.003,Frans H.H. Leenen et al. Hypertension. 2006;48:374-384.,P,0.001,P,=,0.004,P,=,0.036,ALLHAT,亚组分析：脑卒中,6.3,5.4,4,4.5,5,5.5,6,6.5,赖诺普利,氨氯地平,危险降低,23%,6,年中每,1000,例患者卒中发生率,P=0.003,Frans H.H. Leenen et al. Hypertension. 2006;48:374-384.,氨氯地平降低卒中危险，显著优于,ACEI,ALLHAT,病人基线肾功能,:,大部分病人已有肾脏轻中度损害,ALLHAT Collaborative Research Group.,JAMA,. 2002;288:2981-2997.,患者,(%),N=42,418,，随访,5,年,基线平均血压,146 / 84 mmHg,氯噻酮,络活喜,赖诺普利,络活喜,赖诺普利,vs,氯噻酮,vs,氯噻酮,P,值,基线,N14,4928,5898,577,eGFR 77.6 78.0 77.7(mL/min/1.73 m,2,),4,年时,N8,316 4,9244,621,eGFR 70.075.170.7 .001 .03,(mL/min/1.73 m,2,),ALLHAT,：络活喜延缓,eGFR,下降显著优于氯噻酮,*,Baseline mean estimated GFR was 78 mL/min/1.73 m,2,.,ALLHAT Collaborative Research Group.,JAMA,. 2002;288:2981-2997.,ALLHAT:,氨氯地平全程延缓,eGFR,的下降,(,基线,eGFR,90),*,*,*,*,p0.05 vs. Chlorthalidone, lisinopril,Estimated GFR (eGFR) calculated from the simplified MDRD equation,*,*,ALLHAT:,氨氯地平全程延缓,eGFR,的下降,(,基线,eGFR 60-89),*,*,*,*,p0.05 vs. Chlorthalidone, lisinopril,Estimated GFR (eGFR) calculated from the simplified MDRD equation,ALLHAT:,氨氯地平全程延缓,eGFR,的下降,(,基线,eGFR 60),*,*,*,*,p0.05 vs. Chlorthalidone, lisinopril,Estimated GFR (eGFR) calculated from the simplified MDRD equation,有无肾脏保护作用关键是能否将血压降达目标值,如能将血压控制达目标值即能有效保护肾脏此时,CCB,降低血压的效益已能克服其扩张入球小动脉的弊端，而使肾小球内“三高”降低,ALLHAT,的启示,络活喜和,ARB,的经典“,PK”,VALUE,由缬沙坦的生产公司,NOVATIS,赞助,缬沙坦降压治疗对高血压患者,心血管事件的长期评估试验,Valsartan Antihypertensive,Long-term Use Evaluation (,VALUE,) Trial,of Cardiovascular (CV) Events in Hypertension,Julius S et al.,Lancet,. June 2004;363.,在心血管高危的高血压患者，当血压控制在相同水平时，缬沙坦比氨氯地平能更有效地减少心脏病事件的发生率和死亡率。,VALUE:,假 设,Julius S et al.,Lancet,. June 2004;363.,VALUE:,入选对象,治疗或未治疗的高血压患者,未治疗高血压患者的入选标准：,SBP,160210 mmHg,DBP 95105 mmHg,年龄,50,岁，男性或女性,心脏病事件的高危因素, 1,个心血管危险因素或疾病,Mann J, Julius S.,Blood Press,. 1998;7:176183.,VALUE:,主要终点,:,心脏病发生率和死亡率复合事件,Mann J, Julius S.,Blood Press,. 1998;7:176183.,次要终点,致死和非致死性心肌梗死,致死和非致死性脑卒中,致死和非致死性心力衰竭,VALUE:,设 计,选择性加量至目标,BP (140/90 mmHg),Month0.501234 6 *72,A 10 mg +HCTZ 25 mg,A 5 mg,A 10 mg +HCTZ 12.5 mg,A 10 mg,V 80 mg,V 160 mg,V 160 mg +HCTZ 12.5 mg,V 160 mg +HCTZ 25 mg,Amlodipine-based regimen,V 160 mg +HCTZ 25 mg +,Free,add-on,A 10 mg +HCTZ 25 mg +,Free,add-on,Valsartan-based regimen,筛选,随机分组,治疗后校正期,既往治疗(92%),基础上后续治疗,*患者每 6 个月随访一次，共,672,个月.,Julius S et al.,Lancet,. June 2004;363.,VALUE:,收缩压,Julius S et al.,Lancet,. June 2004;363.,缬沙坦,(N= 7649),络活喜,(N = 7596),135,140,145,150,155,mmHg,Months,(,or final visit),不同时间和治疗组坐位,SBP,Baseline,1,24,48,2,3,4,6,12,18,30,36,42,54,60,66,0,1.0,2.0,3.0,4.0,1,24,48,mmHg,2,3,4,6,12,18,30,36,42,54,60,66,Months,(,or final visit),5.0,缬沙坦和络活喜两组,SBP,差,1.0,VALUE:,舒张压,Julius S et al.,Lancet,. June 2004;363.,缬沙坦,(N= 7649),络活喜,(N = 7596),mmHg,Months,(,or final visit),不同时间和治疗组坐位,DBP,mmHg,Baseline,1,24,48,2,3,4,6,12,18,30,36,42,54,60,66,75,85,80,90,0,1.0,2.0,1,24,48,2,3,4,6,12,18,30,36,42,54,60,66,Months,(,or final visit),3.0,缬沙坦和络活喜两组,DBP,差,1.0,4.0,5.0,VALUE:,主要终点(心脏病事件),14,12,10,8,6,4,2,0,Time (months),0 6121824303642 48 54 60 66,Proportion of Patients With First Event (%),Valsartan-based regimen,Amlodipine-based regimen,HR =,1.03; 95% CI = 0.941.14;,P,= 0.49,Julius S et al.,Lancet,. June 2004;363.,Number at risk,Valsartan,Amlodipine,7596,7649,7469,7459,7424,7407,7267,7250,7117,7085,6772,6732,6955,6906,6576,6536,5959,5911,3725,3765,1474,1474,6391,6349,Time (months),Number at risk,Valsartan,Amlodipine,7596,7649,7497,7499,7458,7458,7332,7319,7205,7177,6905,6853,7065,7016,6727,6680,6141,6078,3840,3864,1532,1520,6562,6504,Proportion of Patients With First Event (%),7,6,5,4,3,2,1,0,VALUE:,致死和非致死性心肌梗死,0612182430364248546066,HR =,1.19; 95% CI = 1.02-1.38;,P,= 0.02,Julius S et al.,Lancet,. June 2004;363.,危险降低,19%,缬沙坦为基础的降压方案,络活喜为基础的降压方案,VALUE,：,致死和非致死性脑卒中,危险降低,15%,Julius S et al. Lancet. June 2004;363.,0,1,2,3,4,5,6,0,6,12,18,24,30,36,42,48,54,60,66,缬沙坦为基础的降压方案,络活喜为基础的降压方案,HR =,1.15; 95% CI = 0.98-1.35;,P,= 0.0,8,发生卒中的患者比例,%,VALUE:,临床意义,由于4-12周内更有效地控制血压和达标对减少心血管病事件十分重要，不同降压治疗方案在降压疗效和血压控制达标率方面存在差异，尤其在治疗早期，因此选择更有效、更合理的联合治疗方案有重要意义。,在高危高血压患者的实际临床降压治疗中，二氢吡啶类钙拮抗剂(氨氯地平)为主体的降压治疗模式对减少心脑血管病有较明显的优势。,Julius S et al.,Lancet,. June 2004;363.,VALUE:,结论,高危高血压患者,及早,控制血压,至关重要,Julius S et al.,Lancet,. June 2004;363.,“,这些发现提示控制,BP,达到推荐的目标应在相对短的时间内实现（数周或而非数月），至少对于高危高血压患者应如此。”,Julius,VALUE,研究小组,络活喜,在联合治疗中的优势,ASCOT-BPLA,欧洲最大的高血压研究,-ASCOT,A randomised controlled trial of the prevention of CHD and other vascular events by BP and cholesterol lowering in a factorial study design,ASCOT,研究设计,氨氯地平,培哚普利,阿替洛尔,苄氟噻嗪,19,257 名,高血压患者,PROBE,设计,ASCOT-BPLA,研究者主导, 国际多中心参与,随机、对照研究,安慰剂,阿托伐他汀,10,mg,双盲,ASCOT-LLA,10,305 患者,TC 6.5 mmol/L (250 mg/dL),-10 1.5 3 6,*,12 18 24 Final,ASCOT-BPLA,研究设计,络,10 mg +,培哚普利,8,mg,络 5,mg,络,10 mg +,培哚普利,4,mg,络,10 mg,阿 50,mg,阿,100 mg,阿,100 mg +BFZ 1.25 mg,阿,100 mg + BFZ 2.5 mg,络活喜组,阿,100 mg + BFZ 2.5 mg +,多沙唑嗪,GITS 4mg,络,10 mg +,培哚普利,8,mg +,多沙唑嗪,GITS 4mg,阿替洛尔组,筛选,随机,*患者每 6 个月随访一次,络,10 mg +,培哚普利,8,mg +,多沙唑嗪,GITS 8mg,阿,100 mg + BFZ 2.5 mg +,多沙唑嗪,GITS 8mg,选择性加量至目标,BP140/90 mmHg (,糖尿病,BP130/80mmHg),月,Add others,Add others,Add others, e.g., moxonidine/spironolactone,随机前2/3患者接受降压治疗,Sever PS, et al, for the ASCOT investigators.,J Hypertens.,2001;19:1139-1147.,ASCOT- BPLA,主要终点,比较新型降压药物联合方案,(CCB ACEI,) 与传统降压药物联合方案,(,-,阻滞剂 利尿剂,),对于预防,非致死心肌梗死和致死性冠心病,事件的疗效,主要终点,:,非致死心肌梗死和致死性冠心病,二级终点,脑卒中,全部冠脉事件,首要终点减去无症状心梗,全部心血管事件及操作,心血管死亡,全因死亡,心力衰竭,三级终点,新发糖尿病,肾功能损害,亚组人群中的预设终点,致命性心律失常,病人入组标准,筛选时基线血压,160/100 mm Hg （,未治疗）,140/90 mm Hg （,已经接受一个或多个药物治疗）,年龄 40-79 岁,没有,MI,病史或临床,CHD,3,个或3个以上心血管危险因素,ASCOT,是唯一因为疗效好而两次提前中止的临床研究,ASCOT-LLA,因为立普妥组病人显著获益于2002年9月提前结束，文章发表于2003年,LANCET,杂志,ASCOT-BPLA,2004,年10月,数据安全监察委员会,(,DSMB),由于发现,阿替洛尔,苄氟噻嗪组的病人持续处于不利地位（心血管死亡明显增多）,，建议,ASCOT-BPLA,也应该提前中止, 2005,年6月该研究降压部分提前结束,ASCOT-BPLA：,收缩压和舒张压,mm Hg,60,80,100,120,140,160,180,Time (years),Baseline,0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,5.5,阿替洛尔,苄氟噻嗪,络活喜,培哚普利,137.7,136.1,79.2,77.4,Mean difference 1.9,Last visit,Mean difference 2.7,SBP,DBP,163.9,164.1,94.8,94.5,所有终点总结,The area of the blue square is proportional to the amount of statistical information,络活喜,培哚普利更好,阿替洛尔, 苄氟噻嗪更好,0.50,0.70,1.00,1.45,主要终点,Non-fatal MI (incl silent) + fatal CHD,次要终点,Non-fatal MI (exc. Silent) +fatal CHD,Total coronary end pointTotal CV event and proceduresAll-cause mortalityCardiovascular mortalityFatal and non-fatal strokeFatal and non-fatal heart failure,3,级终点,Silent,MI,Unstable anginaChronic stable anginaPeripheral arterial diseaseLife-threatening arrhythmiasNew-onset diabetes mellitusNew-onset renal impairment,事后分析,Primary end point + coronary revasc procs,CV death + MI + stroke,2.00,Unadjusted Hazard ratio (95% CI),0.90 (0.79-1.02),0.87 (0.76-1.00),0.87 (0.79-0.96),0.84 (0.78-0.90),0.89 (0.81-0.99),0.76 (0.65-0.90),0.77 (0.66-0.89),0.84 (0.66-1.05),1.27 (0.80-2.00),0.68 (0.51-0.92),0.98 (0.81-1.19),0.65 (0.52-0.81),1.07 (0.62-1.85),0.70 (0.63-.078),0.85 (0.75-0.97),0.86 (0.77-0.96),0.84 (0.76-0.92),0.60,0.70,0.80,0.90,1.00,1.50,The area of the black square is proportional to the amount of statistical information,络活喜,培哚普利更好,阿替洛尔,苄氟噻嗪更好,p value,0.02830.0001,0.00010.0030,0.01620.0001,0.00010.0227,0.00150.0001,0.00560.0001,0.00190.0001,0.00010.0055,0.00150.0002,60,years),年轻人 (60,years),女性男性,左室肥厚（根据,ECG or ECHO）,无左室肥厚（根据,ECG or ECHO）,原先有血管病变原先无血管病变,肾功能不全无肾功能不全,有代谢综合症无代谢综合症,所有病人,亚组人群全部心血管事件和操作,络活喜更多获益,:,更多减少,全因死亡,Dahlf B et al. Lancet 2005:366;895-906.,危险降低,11,%,全因死亡患者百分比,%,Number at risk,氨氯地平,培哚普利 96399483 9331 9156 8972 7863,阿替洛尔,苄氟噻嗪 96189461 9274 9059 8843 7720,氨氯地平为基础的降压方案,(n=9639,事件数,738),0.0,1.0,2.0,3.0,4.0,5.0,Years,0.0,2.0,4.0,6.0,8.0,10.0,阿替洛尔为基础的降压方案,(n=9618,事件数,820),HR = 0.89 (0.810.99),P = 0.0247,ASCOT:,与活性药物相比,以氨氯地平为基础的降压方案仍可显著降低全因死亡危险,11,%,络活喜更多获益,:,更多,减少心血管死亡,ASCOT:,与活性药物相比,以氨氯地平为基础的降压方案仍可显著降低心血管死亡危险,24,%,Dahlf B et al. Lancet 2005:366;895-906.,患者数,氨氯地平,培哚普利,96399544 9441 93229167 8078,阿替洛尔,苄氟噻嗪,96189532 9415 92619085 7975,0.0,1.0,2.0,3.0,4.0,5.0,0.0,0.5,1.0,1.5,2.0,2.5,3.0,3.5,氨氯地平组,(263,个事件,),阿替洛尔,组,(342,个事件,),HR = 0.76 (0.650.90),P= 0.0010,Years,危险降低,24,%,Number at risk,氨氯地平,培哚普利 96399475 9337 9168 8966 7863,阿替洛尔,苄氟噻嗪 96189470 9290 9083 8858 7743,0.0,1.0,2.0,3.0,4.0,5.0,Years,0.0,1.0,2.0,3.0,4.0,5.0,HR = 0.90 (0.791.02)p = 0.1052,阿替洛尔,苄氟噻嗪,(No. of events =474),氨氯地平,培哚普利,(No. of events = 429),%,络活喜更多获益：更多减少非致死性心梗和致死性冠,心,病,10%,5,.,5,年,络活喜更多获益：更多减少致死及非致死性,脑,卒中,Number at risk,氨氯地平,培哚普利 96399483 9331 9156 8972 7863,阿替洛尔,苄氟噻嗪 96189461 9274 9059 8843 7720,0.0,1.0,2.0,3.0,4.0,5.0,Years,0.0,1.0,2.0,3.0,4.0,5.0,氨氯地平,培哚普利,(No. of events 327),阿替洛尔,苄氟噻嗪,(No. of events 422),HR = 0.77 (0.660.89),p = 0.0003,%,23%,二级终点,络活喜更多获益：更多减少新发,肾,功能损害,Number at risk,氨氯地平,培哚普利 96399426 9277909388777775,阿替洛尔,苄氟噻嗪 96189431 9247902187827640,HR = 0.85 (0.750.97),p = 0.0187,0.0,1.0,2.0,3.0,4.0,5.0,Years,0.0,1.0,3.0,4.0,5.0,%,2.0,氨氯地平,培哚普利,(No. of events = 403),阿替洛尔,苄氟噻嗪,(No. of events = 469),15%,三级终点,对高血压患者，正确选择初始用药对治疗结果是具有决定性意义的,，,VALUE,、,ALLHAT,和如今的,ASCOT,研究无一例外地证实了这一点。,Peter Sever,教授,（,ASCOT,主要研究者）,阻滞剂,络活喜,利尿剂,ARB,ACEI,阻滞剂,再次强化了长效,CCB,络活喜在,降压治疗中的基础地位,ASCOT,的意义,络活喜,高质量降压,:,更好控制中心动脉压,140,135,130,125,120,115,0 1.0 2.0 3.0 4.0 5.0 6.0,(,年,),133.9,133.2,125.5,121.2,络活喜,组,(n=1042),阿替洛尔组,(n=1031),外周收缩压,:,平均差异,(AUC)=0.7(-0.4-1.7)mmHg,P=0.2,中心收缩压,:,平均差异,(AUC)=4.3(3.3- 5.4)mmHg,P0.0001,收缩压,(mmHg),*,CAFE,研究,:2199,例来自,5,个英国,ASCOT,研究中心的患者,中心动脉压可评估人群为,2073,例,:,络活喜,为基础,的治疗方案组,(n=1042),和阿替洛尔为基础的治疗方案组,(n=1031),。随访,4,年。,Williams B et al. Circulation 2006;113:1213-1225.,降低血压是预防,CVD,的关键,络活喜在,高血压研究中的优势,络活喜,在冠心病治疗中的证据,PREVENT,(,P,rospective,R,andomized,E,valuation of the,V,ascular,E,ffects of,N,orvasc,T,rial ),的结果及其临床意义,络活喜,对于动脉粥样硬化及临床事件发生率的作用,Placebo,3-year follow-up,825,经血管造影证实的，血压控制良好的,CAD,病人,Time (months),-3,-2,-1,0,24,18,12,6,30,36,Pitt B et al.,Circulation,. 2000;102:1503-1510.,QCA,QCA,B-mode carotid ultrasound (n=377),前瞻性，随机，双盲，安慰剂对照，多中心,1,PREVENT:,研究设计,NORVASC 5-10 mg,CAD indicates coronary artery disease; BP, blood pressure; and QCA, quantitative coronary angiography.,X,X,X,X,X,X,X,X,B-,型超声,PREVENT,：入选标准,定量冠状动脉病变：,非供应梗死区心肌，且未接受,PTCA,或,CABG,的血管，至少有一段有轻微病变（,5,20,狭窄）,在一段有局限性狭窄，至少狭窄,30,左主干狭窄,=40%,825,名患者基线时的情况,参数 氨氯地平 安慰剂,患者数,N,417 N,408,平均年龄（岁）,57 57,平均血压（,mmHg,）,129/79 130/79,平均,LDL-C,（,mmol/L) 3.65 3.62,MI,史,44,45,心绞痛史,68,69,得到合格的血管造影图象,43,41,卒中史,3,3,Circulation in Press,825,名患者基线时的情况（续）,参数 氨氯地平 安慰剂,冠脉病变,1,支病变,45,45,2,支病变,35,35,3,支病变,21,21,颈动脉,IMT,（,mm,）,1.2515 1.2508,CCB 33,35,ACE,抑制剂,8,10,利尿剂,12,12,B,阻滞剂,60,66,降脂药,25,29,Circulation in Press,PREVENT,：所有主要事件及操作的发生率,Pitt et al.,Circulation,. 2000. In press.,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),PREVENT:,因不稳定心绞痛住院及主要血管操作,Pitt et al.,Circulation,. 2000. In press.,随访月数,所有血管重建术,安慰剂,氨氯地平,43%,P,=.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,=.01,30.0,25.0,20.0,15.0,10.0,5.0,0.0,0,6,12,18,24,30,36,0,.,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,PREVENT,：络活喜对,B,超测定的颈动脉内膜中层厚度（,IMT,）的作用,内膜中层厚度变化,(mm),Circulation in Press,安慰剂,络活喜,月,PREVENT,的主要结论,与安慰剂组相比，络活喜：,1.,心血管事件显著减少（因心绞痛住院，不需要血管重建术及所有主要临床事件与操作的总和）,2.,显著延缓颈动脉动脉粥样硬化的进展,3.,用,QCA,测定的冠脉平均最小管腔直径变化在络活喜组和安慰剂组无差异,4.,减少冠心病患者住院治疗费用,参考文献：,Circulation 2000, inprinting.,CAMELOT,C,omparison of,A,m,lodipine vs,E,nalapril to,L,imit,O,ccurrences of,T,hrombosis,氨氯地平与依那普利限制血栓发生的比较研究,NORMALISE,N,o,rvasc for,R,egression of,M,anifest,A,therosclerotic,L,esions by,I,ntravascular,S,onographic,E,valuation,血管内超声评价络活喜逆转明显动脉粥样硬化病变,CAMELOT,研究,Nissen et al, for the CAMELOT investigators.,JAMA,. 2004;292:2217-2226.,2004,年,11,月结果发表在,JAMA,杂志,JAMA,. 2004;292:2217-2226,目的：,血压控制到正常,水平的稳定性,CAD,患者，观察,现代常规治疗基础上,加用长效,CCB,氨氯地平,(,络活喜,),或,ACEI,依那普利对,心血管事件和动脉粥样斑块进展,的影响,CAMELOT,研究方案,主要终点:,因冠心病死亡,，,心脏骤停行复苏术，非致死性心肌梗死,，,脑卒中，短暂脑缺血发作,，,冠状动脉旁路移植术（,CABG），,血运重建术,，,因不稳定心绞痛住院,，,需住院治疗的充血性心力衰竭,PTCA=,经皮冠状动脉腔内成形术,.,Nissen et al, for the CAMELOT investigators.,JAMA,. 2004;292:2217-2226.,前瞻、随机、双盲、多中心研究,络活喜,(苯磺酸氨氯地平,) 5-10 mg,依那普利 10-20,mg,安慰剂,PTCA,或血管造影,证实,CAD,患者,血压控制到正常,QCA / IVUS,24 个月,100 个研究中心,1991例患者,临床事件 (发病率和死亡率,)/,斑块进展,IVUS(N=274),CAMELOT：,基线资料,患者的基线特征,均值,(SD),或 患者百分比,安慰剂,(n=655),依那普利,(n=673),络活喜,(n=663),P,值*,年龄,岁,57.2 (9.5),58.5 (9.9),57.3 (9.7),.02,男性,73.0%,71.9%,76.3%,.16,白种人,89.0%,89.3%,89.4%,.97,体重指数,BMI,29.75.0,29.75.5,29.95.5,.72,高血压病史,60.3%,59.7%,61.4%,.82,血压, mm Hg,129/78,129/77,130/78,N/A,血脂异常病史,84.4%,83.7%,83.0%,N/A,LDL-,胆固醇, mg/dL,100 (32),101 (31),104 (32),.,04,糖尿病,19.8%,17.5%,17.3%,.42,不稳定心绞痛,9.9%,8.3%,8.1%,.45,旁路移植手术（,CABG）,史,8.2%,6.8%,8.0%,.59,心机梗死史,37.7%,40.3%,37.4%,.50,目前吸烟者,27.9%,24.8%,27.0%,.41,单支血管病变,28.2%,27.8,%,30.6,%,.47,两支血管病变,34.1,%,36.1,%,32.7,%,.42,三支,血管病变,36.5,%,34.8,%,34.7,%,.74,*通过方差分析或,2,检验计算,.,加拿大心血管学会分级,4,级,.,肉眼估计至少一处狭窄,20%,的血管数,.,Nissen et al, for the CAMELOT investigators.,JAMA,. 2004;292:2217-2226.,CAMELOT：,血压结果,Months After Randomization,Nissen et al, for the CAMELOT investigators.,JAMA,. 2004;292:2217-2226.,Norvasc,(amlodipine besylate),Enalapril,Placebo,Systolic Pressure (mm Hg),132,130,128,126,124,122,120,Diastolic Pressure (mm Hg),80,78,76,74,72,0,1,2,6,9,12,15,18,21,24,总体血压下降均值,络活喜组,- 4.8 / 2.5 mm Hg,依那普利,组,- 4.9 / 2.4,mm Hg,安慰剂,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,(,P,0.001),络活喜组与依那普利组比较，无显著性统计学差异,CAMELOT：,主要复合终点,*心血管死亡,非致死性心肌梗死,心脏骤停行复苏术,冠状动脉血运重建术, 因心绞痛住院,因充血性心力衰竭住院,致死性/非致死性脑卒中或短暂脑缺血发作,任何新发外周血管疾病,.,Nissen et al, for the CAMELOT investigators.,JAMA,. 2004;292:2217-2226.,各时期存在危险性的人数,安慰剂 655588 558525488,依那普利,673608572553529,络活喜663623599574535,累积不良事件比率,月,0,6,12,18,24,0,0.25,0.20,0.15,0.10,0.5,安慰剂,依那普利,络活喜,31%,19%,15%,P=0.16,P=0.10,P=0.003,CAMELOT,亚组研究,NORMALISE,动脉粥样硬化斑块进展,(IVUS),Adapted from Nissen et al, for the CAMELOT investigators.,JAMA,. 2004;292:2217-2226.,安慰剂,(n=49),依那普利,(n=40),络活喜,(n=47),P,均值的患者,N=136,0,0.4,0.8,1.2,1.6,2.0,2.