1、TM 1 999 Pr o fessiona l Postg r a duate Ser v i c e sNormalNormalFattyFattyStreakStreakFibrousFibrousPlaquePlaqueOcclusive Occlusive AtheroscleroticAtheroscleroticPlaquePlaquePlaquePlaqueRupture/Rupture/Fissure&Fissure&ThrombosisThrombosisMIMIStrokeStrokeCritical LegCritical LegIschemiaIschemiaClin
2、ically SilentClinically SilentCoronary Coronary DeathDeathIncreasing AgeIncreasing AgeEffort AnginaEffort AnginaClaudicationClaudicationUnstableUnstableAnginaAnginaAtherosclerosis:A ProgressiveProcessCourtesy of P Ganz.动脉粥样硬化的评价方法A A AB B BB B BA A AA A AIVUSIVUS测测 量量测测 量量 显显 示示，显显 示示，严严 重重严严 重重 狭狭
3、窄窄狭狭 窄窄 不不 是是 活活 动动 病病 变变不不 是是 活活 动动 病病 变变Images supplied by Steven E.Images supplied by Steven E.NissenNissen,MD,Cleveland Clinic.,MD,Cleveland Clinic.B B B破破 裂裂 区区 域域破破 裂裂 区区 域域脂脂 质质脂脂 质质 核核 心心核核 心心粥粥 样样 斑斑 块块管管 腔腔管管 腔腔问题提出：10095908580757001234567动脉粥样硬化的干预-100-80-60-40-200FATS(nicotinic acid+coles
4、tipol)FATS(lovastatin+colestipol)STARS(diet+resin)事件减少狭窄变化-80%-0.9%-0.7%-70%-89%-1.9%CCB的分类CCB的分类CCB的药理作用CIHH3CO2CH3CNHCH2 OCH2 CH2 CO2C2H5吸烟，高血压 LDL,糖尿病炎症内皮功能不全 内皮通透性NO，血管收缩功能异常血小板黏附和聚集细胞因子和细胞黏附分子自由基氧化的LDL进入内皮下间隙增加进入内皮下间隙增加氧化的LDL 被巨噬细胞吞噬泡沫细胞脂质斑块平滑肌细胞增殖和移行生长因子吸引单核细胞（巨噬细胞）AAA氨氯地平可能的干预点氨氯地平可能的干预点AA脂质条
5、纹脂质条纹AAAmlodipine抗动脉粥样硬化作用机制ClassConditions favouring the useCompelling PossibleDiuretics(thiazides)Congestive heart failure;GoutPregancyelderly hypertensives;isolated systolic hypertension;hypertensives of African originDiuretics(loop)Renal insufficiency;congestive heart failureDiuretics Congestive
6、 heart failure;Renal failure;(anti-aldoseterone)post-myocardial infarctionhyperkalaemiab b-BlockersAngina pectoris;Asthma;Peripheral vascularpost-myocardial infarctionchronic obstructivedisease;glucosecongestive heart failurepulmonary disease;intolerance;(up-titration);pregnancey;A-V block athletes
7、andtachyarrhythmias(grade 2 or 3)physically activepatientsCalcium antagonistsElderly patients;Tachyarrhythmias;(dihydropyridines)isolated systolic hypertension;congestive heartangina pectoris;failureperipheral vascular disease;carotid atherosclerosis;pregnancyContraindicationsIndications and contrai
8、ndications for the major classes of antihypertensive drugsA-V,atrioventricular;LV,left ventricular.1975198019851990199520002005临床前临床前临床临床认识到认识到Ca在动粥中的作用在动粥中的作用认识到认识到CCB作用机制的可能益处作用机制的可能益处CCB可抑制可抑制Ca内流入血管壁内流入血管壁 CCB动物（动物（兔子）试验兔子）试验）认识到氨氯地平的独特特点和作用机制认识到氨氯地平的独特特点和作用机制氨氨氨氯地平氨氯地平地平地平猴子试验猴子试验Montreal心脏研究心脏
9、研究MIDASINTACTPREVENTCAMELOT/NORMALIZEVHASELSAINTACT=International Nifedipine Trial on Athrosclerotic Therapy，MIDAS Multicenter Isradipine/Diuretic Atherosclerosis Study Lichtlen et al,Cardiovasc Druds Ther.1990;4:1047-1068.Waters et al,Circulation.1990;82:1940-1953.Borhani et al,JAMA.1996;276:785-79
10、1.Kramsch DM et al,J Hum Hypertens.1995;9(suppl 1):S3-S9注：测量部位为主动脉、主动脉分叉处、颈总动脉和股动脉氧化的氧化的 LDL(mg/dl,平均平均 SD)分组分组 n基线时基线时 18 个月时个月时 p 值值正常对照饮食51.8 1.8 2.8 0.3 NS 致动脉粥样硬化102.1 1.8 18.1 3.230%and 50%918/333-0.0400.012 818/296-0.0590.012-0.0130.050Segments stenosed 50%242/155 0.0850.025 221/139 0.0600.02
11、7-0.0480.097Segments stenosed 0%447/226-0.0800.017 373/195-0.0650.018-0.0600.033Segments stenosed 0%and 30%1324/345-0.0980.009 1175/314-0.0900.010-0.0340.018All segments 2931/354-0.0630.008 2587/324-0.0640.008-0.0200.022Mean change in percent stenosisAll segments 30%diameter stenosis 1770/348 2.940.
12、22 1548/319 3.010.23-0.680.53Segments stenosed 30%and 50%918/333 0.180.39 818/296 0.800.41-1.690.46Segments stenosed 50%241/155-4.740.91 221/139-3.070.95 -4.260.94Segments stenosed 0%447/226 2.790.37 373/195 3.270.39-1.300.33Segments stenosed 0%and 30%1323/345 3.030.26 1175/314 2.840.27-0.540.93All
13、segments 2929/354 1.490.21 2587/324 1.770.22-0.850.30_*Adjusted for coronary segment,clinical center,and angioplasty at baseline.Prespecified primary outcome measure(P50.38)Prespecified secondary outcome measure(additional covariate5baseline diameter stenosis).TABLE 2.Mean Changes in Angiographic Ou
14、tcome Measures During 3 Years of Follow-Up by Treatment Group 0.050.040.030.020.010.00-0.01P=0.0070122436内膜中层厚度变化(mm)Circulation in Press安慰剂络活喜月 Amlodipine Group(n=417)_Placebo Group(n=408)_ EventNo.ofParticipantsWith EventAnnualizedRate per100No.ofParticipantsWith EventAnnualizedRate per100 HR(Amlo
15、dipine/Placebo)95%CI forHR*Life-TableP*_ All-cause mortality 6 0.5 8 0.7 0.74 0.262.12 0.57Major vascular eventsFatal/nonfatal MI 19 1.5 20 1.6 0.94 0.501.76Fatal/nonfatal stroke 5 0.4 5 0.4 0.99 0.293.41Other fatal vascular events 0 0.0 4 0.3Any major vascular event 23 1.8 28 2.3 0.82 0.471.42 0.47
16、Other documented nonfatal vascular eventsCongestive heart failure 1 0.1 5 0.4 0.20 0.021.67Unstable angina 60 4.8 85 6.9 0.67 0.480.93Either event 61 4.9 88 7.2 0.65 0.470.91 0.01Major vascular proceduresCABG 17 1.4 29 2.4 0.57 0.311.03Other major procedure 40 3.2 67 5.5 0.56 0.380.83Either major va
17、scular procedure 53 4.2 86 7.0 0.57 0.410.81 0.001Any major/documented vascular 86 6.9 116 9.5 0.69 0.520.92 0.01event or procedure_*From proportional hazards models(P values presented only for prespecified composite event outcomes).Includes angioplasty,stenting,and arthrectomy.Prespecified event of
18、 interest._TABLE 4.Events and Procedures Occurring During 3 Years of Follow-Up by Treatment Group TABLE 5.Events Recorded in Adverse Experience Logs During 3 Years of Follow-Up by Treatment Group Specified Adverse EventAmlodipine Group(n=417)_Placebo Group(n=408)_ EventNo.ofParticipantsWith EventAnn
19、ualizedRate per100No.ofParticipantsWith EventAnnualizedRate per100 HR(Amlodipine/Placebo)95%CI forHR*Risk Difference/100/y(Amlodipine-Placebo)_ Edema 170 13.6 68 5.6 3.12 2.354.13 8.0Vertigo 17 1.4 3 0.2 5.65 1.6519.23 1.1Constipation 19 1.5 9 0.7 2.11 0.954.65 0.8Erythematous rash 13 1.0 5 0.4 2.57
20、 0.927.19 0.6Dry mouth 10 0.8 3 0.2 3.29 0.9011.90 0.6Gout 4 0.3 10 0.8 0.29 0.081.06 20.5Seborrhea 2 0.2 9 0.7 0.22 0.051.00 20.6Asthenia 25 2.0 37 3.0 0.66 0.401.09 21.0Headache 72 5.8 89 7.3 0.76 0.561.04 21.5Coughing 43 3.4 63 5.1 0.67 0.450.99 21.7Hypertension 17 1.4 39 3.2 0.41 0.230.73 21.8Ch
21、est pain,angina 202 16.1 222 18.1 0.82 0.681.00 22.0_Events with a monitoring P of#0.10 are presented here.*From proportional hazards model._参考文献：参考文献：Circulation 2000,inprinting.参考文献：参考文献：Circulation 2000,inprinting.对PREVENT结果的解释正常血管轻度CAD重度CAD扩张超过代偿:管腔狭窄代偿性扩张：保持固定的管腔进展进展中度CADAdapted from Glagov et
22、al.N Engl J Med.1987;316:1371-1375.消退消退参考文献：参考文献：Circulation 2000,inprinting.参考文献：参考文献：Circulation 2000,inprinting.Coronary AngioPlasty Amlodipine REstenosis StudyPTCA=percutaneous transluminal coronary angioplasty，QCA=quantitative coronary angiography.参考文献:Jorgensen Bet al.J Am Coll Cardiol.1998;31
23、:357C.Coronary AngioPlasty Amlodipine REstenosis StudyCoronary AngioPlasty Amlodipine REstenosis Study参考文献：参考文献：Jrgensen B et al.Results from CAPARES.JACC 1998;31:357C.Coronary AngioPlasty Amlodipine REstenosis Study 多中心多中心,2年年,双盲双盲,随机随机,对照试验对照试验 3000名冠心病患者名冠心病患者 氨氯地平与依那普利和安慰剂比较氨氯地平与依那普利和安慰剂比较 750名患
24、者将用名患者将用IVUS而不是而不是QCA 评价氨氯评价氨氯地平和依那普利对冠状动脉粥样硬化的作用地平和依那普利对冠状动脉粥样硬化的作用 预后指标预后指标:主要冠心病事件总的发生率主要冠心病事件总的发生率患者特点与患者特点与 PREVENT 和和CAMELOT相同相同.共有共有750名患者入选名患者入选在试验前和第在试验前和第24个月作个月作IVUS和和QCA主要终点指标：主要终点指标：目标动脉目标动脉IVUS的斑块总面积的斑块总面积其他观察指标其他观察指标:斑块面积和厚度的变化（新病变）斑块面积和厚度的变化（新病变）;外膜、管腔外膜、管腔和斑块厚度（和斑块厚度（已知病变的变化）。已知病变的变化）。
