老年冠心病治疗策略的演变

老年冠心病治疗策略的演变老年冠心病治疗策略的演变The Strategic Changes of ElderlyCoronary Heart Disease Treatment陈可冀陈可冀 Chen Ke-ji 徐浩徐浩 Xu Hao中国中医科学院西苑医院心血管病中心中国中医科学院西苑医院心血管病中心卫生部中日友好医院全国中西医结合心血管病中心卫生部中日友好医院全国中西医结合心血管病中心 2008-05-23 2老年冠心病临床特点老年冠心病临床特点Clinical Features of Elderly CHDn严重心绞痛多严重心绞痛多/多支血管病变多多支血管病变多/复杂病变多复杂病变多/弥漫和钙化病变多弥漫和钙化病变多/陈旧心梗多陈旧心梗多/左室功能受累左室功能受累多多/并存病多并存病多/无症状多无症状多/合并糖尿病多合并糖尿病多/严重心严重心律失常多律失常多/病死率高病死率高 (高龄者三支病变高龄者三支病变60%-TIME/APPROACH 60%-TIME/APPROACH 试验试验)(75 (75岁岁CHDCHD发病率发病率:男男18.6%,18.6%,女女6.1%)6.1%)(PCI,(PCI,出血并发症出血并发症16.6%)16.6%)n治疗目的治疗目的:缓解症状缓解症状/改善功能改善功能/提高生活质量提高生活质量3冠心病治疗观念的改变冠心病治疗观念的改变Novel Changes in Concept of Elderly CHDTreatment Luminal stenosis to vulnerable plaque formation 从重视管腔狭窄到易损斑块从重视管腔狭窄到易损斑块 Lipid deposit to inflammatory response 从注意脂质沉积到炎症反应从注意脂质沉积到炎症反应 Vulnerable plaque to vulnerable patient 从重视易损斑块到易损病人从重视易损斑块到易损病人Epicardial vessel open to myocardial perfusion从注意心外膜冠脉开通到心肌组织水平灌注从注意心外膜冠脉开通到心肌组织水平灌注Outshine others to trio 从一枝独秀到三驾马车从一枝独秀到三驾马车Single RF control to multi-RF intervention 从单一危险因素控制到多个危险因素联合干预从单一危险因素控制到多个危险因素联合干预Standardized treatment to individualized therapy 从注重规范化治疗到个体化治疗从注重规范化治疗到个体化治疗4Luminal Stenosis管腔狭窄管腔狭窄Vulnerable Plaque易损斑块易损斑块冠心病治疗观念改变之一冠心病治疗观念改变之一First Change in Concept of CHD Treatment5Degree of Coronary Stenosis冠脉狭窄程度冠脉狭窄程度Risk of CHD冠心病严重度冠心病严重度动脉粥样硬化的传统观念动脉粥样硬化的传统观念Traditional Concept of Atherosclerosis?6急性心梗前的冠脉狭窄程度急性心梗前的冠脉狭窄程度Coronary Artery Stenosis pre-AMI70%Bar graph shows severity of coronary artery stenosis before AMI(n=195,4 studies)68%patients had stenosis less than 50%at baseline86%patients had stenosis less than 70%at baseline7降脂疗法降低心脏事件但并不改变管腔狭窄降脂疗法降低心脏事件但并不改变管腔狭窄Lipid-lowering Therapies Decrease Cardiac Events but Not StenosisTrialCholesterol Decrease,%Cardiac Event Decrease,%Change in Stenosis,%FATS2380-1.1 3.7STARS1469-0.53.6STARS2389-1.5 4.0SCRIP16390.32.5PLAC 119740.691.Levine GN,Keaney JF Jr,Vita JA.Cholesterol reduction in cardiovascular disease:clinical benefits and possible mechanisms.N Engl J Med.1995;332:512-521.2.Philbin EF,Pearson TA.How does lipid-lowering therapy rapidly reduce ischemic events?J Myocard Ischemia.1994;6:13-18.3.Pitt B,Mancini GBJ,Ellis SG,Rosman HS,Park J-S,McGovern ME,for the PLAC I investigators.Pravastatin limitation of atherosclerosis in the coronary arteries(PLAC I):reduction in atherosclerosis progression and clinical events.J Am Coll Cardiol.1995;26:1133-11398Coronary Artery Stenosis And Cardiac Events冠脉狭窄与心脏事件冠脉狭窄与心脏事件nPlaque volume or severity of coronary artery stenosis may not be the key factor for inducing cardiac events.n提示提示:冠脉狭窄并非心血管事件关键原因冠脉狭窄并非心血管事件关键原因9Concept of Vulnerable Plaque易损斑块概念的提出易损斑块概念的提出nIn 1989,Muller and colleagues first used“vulnerable plaques”to describe rupture-prone plaques as the underlying cause of most clinical coronary events.首倡易损斑块破裂观念首倡易损斑块破裂观念nA vulnerable plaque often has a large lipid pool,a thin cap,and macrophage-dense inflammation on or beneath its surface.特征特征nVulnerable plaque rupture or disruption causes bleeding into the plaque,luminal thrombosis,and/or vasospasm that may cause sudden flow obstruction and ischemic injury.破裂致血栓形成破裂致血栓形成Muller J,Tofler G,Stone P.Circadian variation and triggers of onset of acute cardiovascular disease.Circulation.1989;79:733743.11多方位策略演变多方位策略演变 Many sided strategic changesn诊断进步诊断进步：由以由以CAG为主导，到重视斑块检测技术的发展如为主导，到重视斑块检测技术的发展如IVUS、OCT；n基础研究方向基础研究方向：逐渐以稳定易损斑块以及减少斑块破裂后血栓形成为方逐渐以稳定易损斑块以及减少斑块破裂后血栓形成为方向向；n二级预防重点二级预防重点：也将由治疗冠脉狭窄转为易损斑块的干预也将由治疗冠脉狭窄转为易损斑块的干预。60 micron CapLesion12CHD develops in 2030 years 冠心病慢性病程冠心病慢性病程Plaque rupture occurs in 23 hrs 斑块破裂快过程斑块破裂快过程DyslipidemiaAtherosclerosisPlaque formationCHD ACSHeart failure LV dysfunction心脏事件的发生心脏事件的发生 Progression of Cardiac Events AMI LV reconstruction13冠脉介入治疗的短处冠脉介入治疗的短处Limitations of PCI nAlthough PCI could relieve severe stenosis of coronary artery,it wouldnt change the biologic course of AS,thus the problem of“unstable”is still unresolved.尚未能解决斑块不稳定问题尚未能解决斑块不稳定问题14COURAGE临床试验临床试验 nBoden WE,et al.Optimal Medical Therapy with or without PCI for Stable coronary Disease(NEJM.356:1503-1516;April 12,2007)15COURAGE 研究设计研究设计Study design of COURAGE trial加加PCI 组组不加不加PCI组组死亡率死亡率/MACE/ACS 2287例稳定型心绞痛患者例稳定型心绞痛患者(他汀类他汀类,抗血小板抗血小板,ACEI/ARB,-,-受体阻滞剂受体阻滞剂)随机化随机化随访随访 2.5-7 Y16两组主要终点比较两组主要终点比较The comparison of endpoints with two groupsn平均随访平均随访4.64.6年年 所有原因死亡或非致死性心肌所有原因死亡或非致死性心肌梗死数梗死数 单纯优化药物治疗组单纯优化药物治疗组:18.5%:18.5%优化药物治疗优化药物治疗+PCI+PCI组组:19.0%:19.0%P=0.62 P=0.6217随访心绞痛缓解率随访心绞痛缓解率Freedom from Angina During Long-Term Follow-upCharacteristicPCI+OMT OMT CLINICALAngina free no.Baseline12%13%1 Yr66%58%3 Yr72%67%5 Yr74%72%The comparison between the PCI group and the medical-therapy group was significant at 1 year(P0.001)and 3 years(P=0.02)but not at baseline or 5 years.18震撼全球心血管病学界震撼全球心血管病学界Grobal impact on cardiological fieldn慢性稳定性冠心病慢性稳定性冠心病/临界狭窄病变者临界狭窄病变者:现代现代药物治疗效果理想药物治疗效果理想/病人依从性好病人依从性好 COURAGE trial:医生应该有信心面对这些病人医生应该有信心面对这些病人 保护病人效果和利益的最大化保护病人效果和利益的最大化 在病人身上做有证据的治疗在病人身上做有证据的治疗 中西医结合应受理解和提倡中西医结合应受理解和提倡19两组总生存率两组总生存率Overall SurvivalNumber at RiskMedical Therapy 1138 1073 1029917 717 468 302 38PCI 1149 1094 1051929 733 488 312 44Years01234560.00.50.60.70.80.91.0PCI+OMTOMT7Hazard ratio:0.8795%CI(0.65-1.16)P=0.3820稳定易损斑块的重要作用稳定易损斑块的重要作用Stabilization of Vulnerable PlaquesnThe vascular pathophysiological research has focused on stabilizing the vulnerable plaque and inhibiting thrombosis after plaque rupture.nThe secondary prevention of CHD also focused on intervention of the vulnerable plaque in addition to treating luminal stenosis of coronary artery.防治重点应是易损斑块防治重点应是易损斑块+狭窄问题狭窄问题1.Kullo IJ,Edwards WD,Schwartz RS.Vulnerable plaque:pathobiology and clinical implications.Ann Intern Med 1998;129(12):1050-60.2.Ozer K,Cilingiroglu M.Vulnerable plaque:definition,detection,treatment,and future implications.Curr Atheroscler Rep.2005;7(2):121-621Lipid Deposit脂质沉积脂质沉积Inflammatory Reaction炎症反应炎症反应冠心病治疗观念改变之二冠心病治疗观念改变之二Second Change in Concept of CHD Treatment 22逾百年之脂质沉积学说逾百年之脂质沉积学说Lipid Deposition Theoryn“Lipid deposition theory”of atherosclerosis has been put forward for 150 years based on the causal relationship between hyperlipidemia and AS.高脂血症与动脉粥样硬化关系高脂血症与动脉粥样硬化关系nThis theory holds that lipid deposition on the artery wall leads to the AS plaques,and it has been dominated the pathogenesis of AS for a long time.Steinberg D,Joseph L，Witztum JL.Lipoproteins and atherogenesis:Current concepts.JAMA 1990;264(23):3047-3052.23Inflammatory theory of AS was first presented by Virchow in 1856.炎症理论的提出炎症理论的提出“Endarteritis deformans”or atheroma-a product of an inflammatory process within the intima with the fibrous thickening evolved as a consequence of a reactive fibrosis induced by proliferating connective tissue cells within the intima.The theory did not raise great attention at that time.当年未获当年未获关注关注动脉粥样硬化炎症学说动脉粥样硬化炎症学说Inflammation Theory24nIn recent years,AS was shown to have the basic manifestation of inflammation 炎症反应的基本表现炎症反应的基本表现nDegenerationnExudation nProliferationnThe cell-cell interaction is similar to other chronic inflammation diseases such as rheumatoid arthritis,chronic pancreatitis and hepatic cirrhosis.n AS was no longer regarded as a simple disease of lipid deposition in the vessel wall,but also an advanced inflammatory reaction.n In AS plaque of human,there was also evidence of several pathogens 病原病原nChlamydia pneumoniaenCytomegalovirusnHerpes virusnHelicobacter pylori动脉粥样硬化炎症学说动脉粥样硬化炎症学说Inflammation Theory25动脉粥样硬化炎症学说动脉粥样硬化炎症学说Inflammation TheoryIn 1999,a century later,Ross declared that AS is one of chronic inflammatory disease,based on his injury reaction theory.损伤反应理论的提出损伤反应理论的提出(Ross,1999)26动脉粥样硬化的新概念动脉粥样硬化的新概念The New Concept of ASTraditional-“Rust in a pipe”(管腔生锈管腔生锈)Passive lipid deposition onto vessel wallCurrent-“A fire within”(管壁着火管壁着火)Active inflammatory reaction inside vessel wall27Inflammatory BiomarkersAS炎症生物学标志物炎症生物学标志物Inflammatory Biomarkers白介素白介素-6反应蛋白反应蛋白单核细胞趋化因子单核细胞趋化因子-1血清淀粉样蛋白血清淀粉样蛋白肿瘤坏死因子肿瘤坏死因子白介素白介素-18白介素白介素-10 细胞间黏附分子细胞间黏附分子血管细胞黏附分子血管细胞黏附分子E-选择素选择素血管性假血友病因子血管性假血友病因子髓过氧化物酶髓过氧化物酶磷脂酶磷脂酶血浆脂蛋白相关性磷脂酶血浆脂蛋白相关性磷脂酶血管内皮生长因子血管内皮生长因子胎盘生长因子胎盘生长因子肝细胞生长因子肝细胞生长因子基质金属蛋白酶基质金属蛋白酶1，2，9妊娠相关血浆蛋白妊娠相关血浆蛋白-ACD40配体配体P-选择素选择素28AS炎症生物学标志物炎症生物学标志物Hs-CRPC-Reactive Protein in CVDnElevated hs-CRP levels in healthy populations predict vascular events such as MI and stroke as well as the development of diabetes.nHs-CRP is a useful biomarker in risk prediction and treatment outcome assessment.nHs-CRP was also implicated directly in atherogenesis.CRP has been found in human atherosclerotic plaque and shown to cause endothelial cell dysfunction,oxidant stress and intimal hypertrophy in experimental models.nIt could also be a potential target of AS treatment and prevention.高敏高敏C C反应蛋白增高反应蛋白增高Wilson AM,Ryan MC,Boyle AJ.The novel role of C-reactive protein in cardiovascular disease:risk marker or pathogen.Int J Cardiol.2006;106(3):291-7.29基于几种生化标记物的心血管事件相对风险基于几种生化标记物的心血管事件相对风险01.02.04.06.0Lipoprotein(a)LDLCHomocysteineTCApolipoprotein BTC:HDLChs-CRPhs-CRP+TC:HDLCRelative Risk of Future CV EventsCV,cardiovascular;TC,total cholesterol;LDLC,low-density lipoprotein cholesterol;HDL-C,high-density lipo-protein cholesterol;CRP,C-reative protein;hs-CRP,high-sensitivity C-reactive protein;TC,total cholesterol.Adapted from Rifai N,et al.Clin Chem.2001;47:28-30.30hs-CRP(mg/L)他汀治疗他汀治疗6 6周对周对hs-CRP水平的影响水平的影响The influence of Statins on hs-CRP levelJialal I et al.Circulation 2001;103:1933-1935.6543210Baseline*Prava(40 mg/d)Simva(20 mg/d)Atorva(10 mg/d)*p0.025 vs.Baseline31ENHANCE试验的启示试验的启示Enlightenment from ENHANCE trialKastelein,JJ.NEJM.April 3,2008;P.1431-144332冠心病治疗策略的更新冠心病治疗策略的更新Therapeutic Strategies for CHDnEvidence based approach Despite regulating blood lipid metabolism,statins should be recommended in its anti-inflammation and other protective effects on cardiovascular diseases.推荐他汀药物的应用推荐他汀药物的应用nAnti-inflammation-several strategies that interfere with inflammation are in progress.一些干予炎症治疗策略在发展中一些干予炎症治疗策略在发展中Ozer K,Cilingiroglu M.Vulnerable plaque:definition,detection,treatment,and future implications.Curr Atheroscler Rep.2005;7(2):121-6.33Vulnerable Plaque易损斑块易损斑块Vulnerable Patient易损病人易损病人冠心病治疗观念改变之三冠心病治疗观念改变之三Third Change in Concept of CHD Treatment 34易损病人概念的提出易损病人概念的提出Definition of Vulnerable PatientnVulnerable plaques are not the only culprit factors.Vulnerable blood and vulnerable myocardium play an important role in for the development of acute coronary syndromes,myocardial infarction,and sudden cardiac death.n“Vulnerable patient is proposed to define subjects susceptible to an acute coronary syndrome or sudden cardiac death based on plaque,blood,or myocardial vulnerability.Naghavi M.et al.Circulation 2003;108(14):1664-72.易损病人易损病人=易损斑块易损斑块+易损血液易损血液+易损心肌易损心肌35 nA quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables listed below.nVulnerable plaques 易损斑块易损斑块nprone to rupture 易于破裂易于破裂nwith high likelihood of thrombotic complications and rapid progressionnPlaque rupture accounts for nearly 70%of fatal AMI and/or sudden coronary deathsnVulnerable plaque is the main,but not the unique cause for acute cardiovascular eventsnVulnerable blood 易损血液易损血液nprone to thrombosis 易于血栓形成易于血栓形成nVulnerable myocardium 易损心肌易损心肌nprone to fatal arrhythmia 易发生致命性心律失常易发生致命性心律失常易损病人易损病人Vulnerable Patient36治疗上的创新性发展治疗上的创新性发展Development of Innovative Therapies脂质沉积脂质沉积 Lipid deposit调节血脂调节血脂 Regulating Blood Lipid药物药物:扩冠扩冠 Drugs：Nitrates,CaA手术手术 Surgery：PCI、CABG稳定斑块稳定斑块 Stabilizing Plaque,抗炎抗炎 anti-inflammatory，抗栓抗栓(抗血小板、抗凝抗血小板、抗凝)Anti-thrombosis(anti-platelet,anticoagulation)早期识别；重预防早期识别；重预防 Early Identification and Prevention冠脉狭窄冠脉狭窄Coronary Stenosis易损斑块、破裂、血栓形成易损斑块、破裂、血栓形成 Vulnerable Plaque,Rupture,Thrombosis易损患者易损患者Vulnerable Patients37血脂康血脂康现代中药现代中药Xuezhikang Modern Chinese Herbal MedicineMaterial:special produced red yeast rice原料：特制红曲原料：特制红曲Method:red yeast rice(Oriza Sative L.)is grown on nutrient agar and special red yeast added,then fermented using modern biological technology to make the effective compound.方法：粳米加入培养液，接入特殊的红方法：粳米加入培养液，接入特殊的红曲霉菌种，运用现代生物技术发酵而成。曲霉菌种，运用现代生物技术发酵而成。38ResultCARECCSPSTC-20%-13%LDL-C-28%-20%1st terminationNon-lethal AMI&CHD death-24%(P=0.003)-45%(P0.0001)Total CHD death-24%(P0.05）-33%(P=0.0003)CARE vs.CCSPS 39CCSPS亚组分析亚组分析血脂康广泛适用于特殊人群的调脂治疗血脂康广泛适用于特殊人群的调脂治疗n合理合理积极积极谨慎谨慎n老年人群老年人群n高血压人群高血压人群n糖尿病人群糖尿病人群40日本日本MEGA STUDY结果表明结果表明:东方人群温和调脂即可明显获益东方人群温和调脂即可明显获益,与与CCSPSCCSPS结果一致结果一致 MEGA Studys result:similar to CCSPS对日本人的一级预防对日本人的一级预防:服用服用10-20mg的的pravastatin可使冠心病危险可使冠心病危险33%;与美欧用与美欧用20-40mg效益相当效益相当对轻中度对轻中度Tc增高的东方人群低剂量是安全有效的增高的东方人群低剂量是安全有效的Atheroscler Suppl.2007 Aug;8(2):13-7.Epub 2007 Jun 22.LinksPrimary prevention of cardiovascular diseases among hypercholesterolemic Japanese with a low dose of pravastatin.Nakamura H;MEGA Study Group.Tokyo,Japan-Results of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese(MEGA)study,the first large-scale primary-prevention trial in a Japanese population that showed statin therapy reduces the risk of coronary heart disease(CHD),have now been published in the September 30,2006 issue of the Lancet.MEGA,first presented by lead author Dr Haruo Nakamura(National Defense Medical College,Saitama,Japan)at the American Heart Association Scientific(AHA)Sessions 2005 in Dallas,TX,showed that the addition of pravastatin 10 mg to a low-fat diet rich in omega-3 fatty acids reduces the risk of CHD in Japanese individuals with moderately elevated cholesterol levels by 33%,approximately the same reduction observed in US and European primary-prevention trials that have used larger statin doses.41Platelets are inflammatory cells血小板实乃炎症细胞血小板实乃炎症细胞42EBM 研究所得研究所得(Aspirin)Experience from EBM43抗血小板治疗的困惑抗血小板治疗的困惑Certain puzzled problem on anti-platelet therapyn颅内出血胃肠道出血鼻腔出血胸膜腔出血皮颅内出血胃肠道出血鼻腔出血胸膜腔出血皮下出血下出血（aspirin 75-100mg/d,clopidogril 75mg/d)n高龄尤多见高龄尤多见;远超远超1.8-2.1（CURE 研究）研究）n可适当减量（包括首剂负荷量）可适当减量（包括首剂负荷量）44Aspirin resistanceAspirin resistance概念的争议n临床临床Aspirin resistanceAspirin resistance:减少事件减少事件/未能消除事件未能消除事件 AAAA基因多态性基因多态性/无效或不利结果无效或不利结果n生化生化Aspirin resistanceAspirin resistance:出血时间延长出血时间延长/TXA2/TXA2抑制合成抑制合成/刺激血小板聚集刺激血小板聚集 0.4-83.0%0.4-83.0%Dalen JE,et al:Am Dalen JE,et al:Am J Med,2007,120:1-4 J Med,2007,120:1-4 Loordkipandize M,et al:Pharmaco Loordkipandize M,et al:Pharmaco Ther,2006,112:733-743 Ther,2006,112:733-743 45川芎嗪抗血小板作用川芎嗪抗血小板作用Anti-platelet Effects of LigustrazineThe active component of ABC herb-Ligusticum Chuanxiong 活血化瘀药川芎主要成分活血化瘀药川芎主要成分nAlkaloids 生物碱类生物碱类 (Tetramethypyrazine,Ligustrazine)nLactones 内酯类内酯类 四甲基吡嗪四甲基吡嗪nPhenols 酚性化合物酚性化合物nFerulic acid 阿魏酸阿魏酸nOthers 其它其它46活血药抗活血药抗TXATXA2 2生成生成Inhibitory Effects of ABC-herbs on TXA2 Production 芎芍胶囊干预治疗研究芎芍胶囊干预治疗研究XS0601 Reduces the Incidence of Restenosis Post-PCI (RIRE Trial,National Project)川芎有效部位川芎有效部位 Paeoniflorin赤芍有效部位赤芍有效部位 Chuanxingol(国家十五攻关课题国家十五攻关课题)安贞医院同仁医院中日友好医院安贞医院同仁医院中日友好医院西苑医院广东省中医院西苑医院广东省中医院48 335 cases enrolled 335例入选例入选 Control group对照组对照组 169 casesTreatment group治疗组治疗组 166 cases308 cases completed with 147 repeat angiography 308例完成试验，例完成试验，147例重复冠脉造影例重复冠脉造影Randomized随机随机3 cases lost脱落脱落12 cases exclude剔除剔除3 cases lost脱落脱落9 cases exclude剔除剔除154 cases154 cases(47.4%)49Comparison of clinical end-point event 两组临床终点事件的比较两组临床终点事件的比较 Note:There was significant difference between the two groups(p0.05).Death 死亡死亡0 0.00 00.00 Nonfatal MI 非致命性心梗非致命性心梗1 0.64 10.64 Repeat PCI 重复介入治疗重复介入治疗15 1.91 314.46 Event终点事件终点事件Treatment 治疗组治疗组Control 对照组对照组 N(%)N (%)CABG 冠脉搭桥冠脉搭桥 00.00 30.00 干预干预PCI术后再狭窄临床结果比较术后再狭窄临床结果比较 注注:两组比较有显著性差异两组比较有显著性差异(p0.05).50Kaplan-Meier Survival CurveClinical Follow-up Time(day)400350300250200150100500Cum No-event Survival1.00.90.80.70.60.50.40.30.20.100.00 XS0601TreatmentStandard TreatmentP 0.05生存率比较生存率比较XS0601 Improves Cumulative No-Event Survival51Integrative Medicine:The Experience from China结合医学经验：来自中国结合医学经验：来自中国52HS-CRP MCP-1 TNF-CD68Hs-CRP:Hypersensitive C-reaction Protein;MCP-1:Monocyte Chemoattractant Protein;TNF-:Tumor Necrosis Factor-ABC+D药物对炎症指标变化比较药物对炎症指标变化比较Results:Inflammatory Marker Changes53 老年冠心病治疗多元模式老年冠心病治疗多元模式Multiple Patterns for Elderly CHD Treatmentn优化药物治疗优化药物治疗(证据和达标问题证据和达标问题)nPCI(Cypher/TAXUS,安全性安全性/适应症的长期考察适应症的长期考察)nCABG(搭桥与药物支架不能相互替代搭桥与药物支架不能相互替代/在左主干和在左主干和/或多支病变或多支病变/或一支多处病变或一支多处病变/钙化比较严重的治疗中有钙化比较严重的治疗中有优势优势)n心理干预心理干预n多元模式互补多元模式互补54心外膜心外膜冠脉开通冠脉开通心肌组织水平心肌组织水平灌注灌注冠心病治疗观念改变之四冠心病治疗观念改变之四Fourth Change in Concept of CHD Treatment 55n再灌注治疗是再灌注治疗是AMI治疗的里程碑，从被动、保守转为主动、积极的治疗的里程碑，从被动、保守转为主动、积极的血运重建，挽救了无数患者的生命血运重建，挽救了无数患者的生命n但临床发现，但临床发现，约约10-30%10-30%患者患者PCI成功后，心肌组织水平成功后，心肌组织水平无再灌注，即无复流现象无再灌注，即无复流现象n无复流是无复流是PCI后死亡和心梗的独立预测因素后死亡和心梗的独立预测因素无复流现象的反思无复流现象的反思Asking in reply on no-flowFrederic SR,et al.Am Heart J 2003;145:42-46.56可能的机制可能的机制Possible mechanism可能的机制可能的机制微血管结构完整性破坏微血管结构完整性破坏微栓子栓塞微栓子栓塞白细胞聚集白细胞聚集微血管功能完整性损伤，微血管功能完整性损伤，主要是痉挛所致主要是痉挛所致血小板激活血小板激活氧自由基氧自由基57策略演变策略演变Strategic change 回顾再灌注历史：过去回顾再灌注历史：过去2020年基本上是心外膜冠年基本上是心外膜冠状动脉再灌注的状动脉再灌注的2020年，相信未来的年，相信未来的1010年将是微循环年将是微循环灌注的灌注的1010年年n检测手段检测手段：n冠脉微循环灌注评价：心肌声学造影成为热点冠脉微循环灌注评价：心肌声学造影成为热点n防治手段防治手段：n无复流防治：腺苷、无复流防治：腺苷、CaACaA，活血化瘀中药等，活血化瘀中药等n微循环改善剂：未来冠心病研究方向之一？微循环改善剂：未来冠心病研究方向之一？Diabetes Care 29:202206,2006Circ J 2006;70:1099 1104)58一枝独秀一枝独秀三驾马车三驾马车冠心病治疗观念改变之五冠心病治疗观念改变之五Fifth Change in Concept of CHD Treatment 59“药物支架时代药物支架时代”来临？来临？The trend of the DES times?nDES的出现，使心血管介入技术向前迈的出现，使心血管介入技术向前迈进了一大步，进了一大步，成为冠心病介入治疗的第成为冠心病介入治疗的第3个里程碑个里程碑。nBMS、冠脉搭桥术、冠脉搭桥术以及传统药物治疗是以及传统药物治疗是否真的要淡出舞台否真的要淡出舞台 60Serruys PW,Kutryk MJB,Ong ATL.Coronary-artery stents.N Engl J Med 2006;354:483-495.61FDA 05/12/2006:药物支架要求一万例验证三年药物支架要求一万例验证三年nFDA:Heart patients with drug-coated stents face blood-clot riskBy Associated PressTuesday,December 5,2006 WASHINGTON-Patients implanted with drug-coated stents to hold open their choked arteries face a small but significant risk of blood clots,health officials said Tuesday,and a new study recommended they take clot-busting medications indefinitely.n Growing concerns about the long-term safety of drug-coated stents comes to a head this week,when the Food and Drug Administration convenes a two-day meeting to discuss clotting risks associated with the devices.n In documents released Tuesday,the FDA said it is unknown whether there is an increased risk of death or heart attack in patients fitted with the so-called drug-eluting stents.However,those patients do face an increased risk of blood clots a year or more after surgery compared with those fitted with bare-metal stents,the agency said in citing recent studies.n Natick,Mass.-based Boston Scientific Corp.and New Brunswick,N.J.-based Johnson&Johnson are the only two companies approved to sell the drug-coated versions.n The FDA is seeking advice on a wide range of questions on the popular stents,including whether to update their labels with new warnings,identify patients for whom they arent appropriate and perhaps change federal recommendations on how long people should take blood thinners like Plavix and aspirin following stent surgery.62Stent vs CABGn国际上正在组织三个大规模随机对照临床研究进行多支血管病的DES和CABG疗效评估，相信这些研究将有助于明确二者各自的优势和适应证。nFREDOOM:多支血管病合并糖尿病患者的DES和CABG的对比研究；nSYNTAX:左主干和(或)多支血管病的DES和CABG对比研究；nCOMBAT:左主干和(或)多支血管病的DES和CABG的对比研究。63目前认识目前认识Understanding at presentnDES总体是有较好效果的，但长期应用安全性仍有待总体是有较好效果的，但长期应用安全性仍有待大规模临床试验加以验证；大规模临床试验加以验证；nDES术后更应强调坚持规范二联抗血小板治疗，至少术后更应强调坚持规范二联抗血小板治疗，至少1年以上，以减少支架血栓的发生；年以上，以减少支架血栓的发生；n大约大约6075%接受接受DES治疗的患者实际上并不一定治疗的患者实际上并不一定需要需要DES，临床应严格掌握适应症；，临床应严格掌握适应症；64Stent vs CABGn在左主干和在左主干和/或多支病变中，或多支病变中，CABG有优有优势势;n在美国，只有在美国，只有18%的左主干和的左主干和/或三支或三支病变患者选择支架植入病变患者选择支架植入;n在欧洲，在复杂病变血运重建中，在欧洲，在复杂病变血运重建中，CABG仍占有主导优势。仍占有主导优势。65关注冠心病关注冠心病Hybrid技术技术Pay attention to Hybrid treatmentn冠心病杂交手术(Hybrid技术)：联合应用介入治疗/搭桥手术,优势互补,一站式完成 再血管化,是冠心病治 疗的重要发展方向。66Life Wide Open开放生命开放生命67危险因素危险因素单一控制单一控制危险因素危险因素复杂干预复杂干预冠心病治疗观念改变之六冠心病治疗观念改变之六Sixth Change in Concept of CHD Treatment 68DiabetesDyslipidemiaHypertensionObesity69多重危险因素的干预多重危险因素的干预Interventions for multi-RFn单一危险因素的治疗常可使病人心脑血单一危险因素的治疗常可使病人心脑血管病危险下降管病危险下降20%20%30%30%，意味着还有意味着还有70%70%80%80%的剩余危险需要降低的剩余危险需要降低 70Polypill:心