老年冠心病治疗策略的演变

老年冠心病治疗策略的演变THESTRATEGICCHANGESOFELDERLYCORONARYHEARTDISEASETREATMENT陈可冀CHENKEJI徐浩XUHAO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200805231老年冠心病临床特点CLINICALFEATURESOFELDERLYCHDN严重心绞痛多/多支血管病变多/复杂病变多/弥漫和钙化病变多/陈旧心梗多/左室功能受累多/并存病多/无症状多/合并糖尿病多/严重心律失常多/病死率高高龄者三支病变60TIME/APPROACH试验75岁CHD发病率男186,女61PCI,出血并发症166N治疗目的缓解症状/改善功能/提高生活质量2冠心病治疗观念的改变NOVELCHANGESINCONCEPTOFELDERLYCHDTREATMENTLUMINALSTENOSISTOVULNERABLEPLAQUEFORMATION从重视管腔狭窄到易损斑块LIPIDDEPOSITTOINFLAMMATORYRESPONSE从注意脂质沉积到炎症反应VULNERABLEPLAQUETOVULNERABLEPATIENT从重视易损斑块到易损病人EPICARDIALVESSELOPENTOMYOCARDIALPERFUSION从注意心外膜冠脉开通到心肌组织水平灌注OUTSHINEOTHERSTOTRIO从一枝独秀到三驾马车SINGLERFCONTROLTOMULTIRFINTERVENTION从单一危险因素控制到多个危险因素联合干预STANDARDIZEDTREATMENTTOINDIVIDUALIZEDTHERAPY从注重规范化治疗到个体化治疗3LUMINALSTENOSIS管腔狭窄VULNERABLEPLAQUE易损斑块冠心病治疗观念改变之一FIRSTCHANGEINCONCEPTOFCHDTREATMENT4DEGREEOFCORONARYSTENOSIS冠脉狭窄程度RISKOFCHD冠心病严重度动脉粥样硬化的传统观念TRADITIONALCONCEPTOFATHEROSCLEROSIS5急性心梗前的冠脉狭窄程度CORONARYARTERYSTENOSISPREAMI70OFDIAMETERSTENOSISOFTHEPATIENTSBARGRAPHSHOWSSEVERITYOFCORONARYARTERYSTENOSISBEFOREAMIN195,4STUDIES68PATIENTSHADSTENOSISLESSTHAN50ATBASELINE86PATIENTSHADSTENOSISLESSTHAN70ATBASELINEFALKETALCIRCULATION1995926576降脂疗法降低心脏事件但并不改变管腔狭窄LIPIDLOWERINGTHERAPIESDECREASECARDIACEVENTSBUTNOTSTENOSISTRIALCHOLESTEROLDECREASE,CARDIACEVENTDECREASE,CHANGEINSTENOSIS,FATS23801137STARS14690536STARS23891540SCRIP16390325PLAC119740691LEVINEGN,KEANEYJFJR,VITAJACHOLESTEROLREDUCTIONINCARDIOVASCULARDISEASECLINICALBENEFITSANDPOSSIBLEMECHANISMSNENGLJMED19953325125212PHILBINEF,PEARSONTAHOWDOESLIPIDLOWERINGTHERAPYRAPIDLYREDUCEISCHEMICEVENTSJMYOCARDISCHEMIA1994613183PITTB,MANCINIGBJ,ELLISSG,ROSMANHS,PARKJS,MCGOVERNME,FORTHEPLACIINVESTIGATORSPRAVASTATINLIMITATIONOFATHEROSCLEROSISINTHECORONARYARTERIESPLACIREDUCTIONINATHEROSCLEROSISPROGRESSIONANDCLINICALEVENTSJAMCOLLCARDIOL199526113311397CORONARYARTERYSTENOSISANDCARDIACEVENTS冠脉狭窄与心脏事件NPLAQUEVOLUMEORSEVERITYOFCORONARYARTERYSTENOSISMAYNOTBETHEKEYFACTORFORINDUCINGCARDIACEVENTSN提示冠脉狭窄并非心血管事件关键原因8CONCEPTOFVULNERABLEPLAQUE易损斑块概念的提出NIN1989,MULLERANDCOLLEAGUESFIRSTUSED“VULNERABLEPLAQUES”TODESCRIBERUPTUREPRONEPLAQUESASTHEUNDERLYINGCAUSEOFMOSTCLINICALCORONARYEVENTS首倡易损斑块破裂观念NAVULNERABLEPLAQUEOFTENHASALARGELIPIDPOOL,ATHINCAP,ANDMACROPHAGEDENSEINFLAMMATIONONORBENEATHITSSURFACE特征NVULNERABLEPLAQUERUPTUREORDISRUPTIONCAUSESBLEEDINGINTOTHEPLAQUE,LUMINALTHROMBOSIS,AND/ORVASOSPASMTHATMAYCAUSESUDDENFLOWOBSTRUCTIONANDISCHEMICINJURY破裂致血栓形成MULLERJ,TOFLERG,STONEPCIRCADIANVARIATIONANDTRIGGERSOFONSETOFACUTECARDIOVASCULARDISEASECIRCULATION198979733743910多方位策略演变MANYSIDEDSTRATEGICCHANGESN诊断进步由以CAG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；N二级预防重点也将由治疗冠脉狭窄转为易损斑块的干预。005）33P00003CAREVSCCSPS38CCSPS亚组分析血脂康广泛适用于特殊人群的调脂治疗N合理积极谨慎N老年人群N高血压人群N糖尿病人群39日本MEGASTUDY结果表明东方人群温和调脂即可明显获益,与CCSPS结果一致MEGASTUDYSRESULTSIMILARTOCCSPS对日本人的一级预防服用1020MG的PRAVASTATIN可使冠心病危险33与美欧用2040MG效益相当对轻中度TC增高的东方人群低剂量是安全有效的ATHEROSCLERSUPPL2007AUG82137EPUB2007JUN22LINKSPRIMARYPREVENTIONOFCARDIOVASCULARDISEASESAMONGHYPERCHOLESTEROLEMICJAPANESEWITHALOWDOSEOFPRAVASTATINNAKAMURAHMEGASTUDYGROUPTOKYO,JAPANRESULTSOFTHEMANAGEMENTOFELEVATEDCHOLESTEROLINTHEPRIMARYPREVENTIONGROUPOFADULTJAPANESEMEGASTUDY,THEFIRSTLARGESCALEPRIMARYPREVENTIONTRIALINAJAPANESEPOPULATIONTHATSHOWEDSTATINTHERAPYREDUCESTHERISKOFCORONARYHEARTDISEASECHD,HAVENOWBEENPUBLISHEDINTHESEPTEMBER30,2006ISSUEOFTHELANCETMEGA,FIRSTPRESENTEDBYLEADAUTHORDRHARUONAKAMURANATIONALDEFENSEMEDICALCOLLEGE,SAITAMA,JAPANATTHEAMERICANHEARTASSOCIATIONSCIENTIFICAHASESSIONS2005INDALLAS,TX,SHOWEDTHATTHEADDITIONOFPRAVASTATIN10MGTOALOWFATDIETRICHINOMEGA3FATTYACIDSREDUCESTHERISKOFCHDINJAPANESEINDIVIDUALSWITHMODERATELYELEVATEDCHOLESTEROLLEVELSBY33,APPROXIMATELYTHESAMEREDUCTIONOBSERVEDINUSANDEUROPEANPRIMARYPREVENTIONTRIALSTHATHAVEUSEDLARGERSTATINDOSES40PLATELETSAREINFLAMMATORYCELLS血小板实乃炎症细胞41EBM研究所得ASPIRINEXPERIENCEFROMEBM42抗血小板治疗的困惑CERTAINPUZZLEDPROBLEMONANTIPLATELETTHERAPYN颅内出血胃肠道出血鼻腔出血胸膜腔出血皮下出血（ASPIRIN75100MG/D,CLOPIDOGRIL75MG/DN高龄尤多见远超1821（CURE研究）N可适当减量（包括首剂负荷量）43ASPIRINRESISTANCE概念的争议N临床ASPIRINRESISTANCE减少事件/未能消除事件AA基因多态性/无效或不利结果N生化ASPIRINRESISTANCE出血时间延长/TXA2抑制合成/刺激血小板聚集04830DALENJE,ETALAMJMED,2007,12014LOORDKIPANDIZEM,ETALPHARMACOTHER,2006,11273374344川芎嗪抗血小板作用ANTIPLATELETEFFECTSOFLIGUSTRAZINETHEACTIVECOMPONENTOFABCHERBLIGUSTICUMCHUANXIONG活血化瘀药川芎主要成分NALKALOIDS生物碱类TETRAMETHYPYRAZINE,LIGUSTRAZINENLACTONES内酯类四甲基吡嗪NPHENOLS酚性化合物NFERULICACID阿魏酸NOTHERS其它45活血药抗TXA2生成INHIBITORYEFFECTSOFABCHERBSONTXA2PRODUCTION46芎芍胶囊干预治疗研究XS0601REDUCESTHEINCIDENCEOFRESTENOSISPOSTPCIRIRETRIAL,NATIONALPROJECT川芎有效部位PAEONIFLORIN赤芍有效部位CHUANXINGOL国家十五攻关课题安贞医院同仁医院中日友好医院西苑医院广东省中医院47临床研究流程临床研究流程SURVEYOFSTUDY335CASESENROLLED335例入选CONTROLGROUP对照组169CASESTREATMENTGROUP治疗组166CASES308CASESCOMPLETEDWITH147REPEATANGIOGRAPHY308例完成试验，147例重复冠脉造影RANDOMIZED随机3CASESLOST脱落12CASESEXCLUDE剔除3CASESLOST脱落9CASESEXCLUDE剔除154CASES154CASES47448COMPARISONOFCLINICALENDPOINTEVENT两组临床终点事件的比较NOTETHEREWASSIGNIFICANTDIFFERENCEBETWEENTHETWOGROUPSP005DEATH死亡00000000NONFATALMI非致命性心梗10641064REPEATPCI重复介入治疗1519131446EVENT终点事件TREATMENT治疗组CONTROL对照组NNCABG冠脉搭桥00003000干预PCI术后再狭窄临床结果比较注两组比较有显著性差异P00549XS0601TREATMENTSTANDARDTREATMENTP005生存率比较XS0601IMPROVESCUMULATIVENOEVENTSURVIVAL50INTEGRATIVEMEDICINETHEEXPERIENCEFROMCHINA结合医学经验来自中国51HSCRPMCP1TNFCD68CONTROLDANSHENCHISHAOCHUANXIONGSANQIJIUDAHUANGTAORENCPHSCRPHYPERSENSITIVECREACTIONPROTEINMCP1MONOCYTECHEMOATTRACTANTPROTEINTNFTUMORNECROSISFACTORABCD药物对炎症指标变化比较RESULTSINFLAMMATORYMARKERCHANGES52老年冠心病治疗多元模式MULTIPLEPATTERNSFORELDERLYCHDTREATMENTN优化药物治疗证据和达标问题NPCICYPHER/TAXUS,安全性/适应症的长期考察NCABG搭桥与药物支架不能相互替代/在左主干和/或多支病变/或一支多处病变/钙化比较严重的治疗中有优势N心理干预N多元模式互补53心外膜冠脉开通心肌组织水平灌注冠心病治疗观念改变之四FOURTHCHANGEINCONCEPTOFCHDTREATMENT54N再灌注治疗是AMI治疗的里程碑，从被动、保守转为主动、积极的血运重建，挽救了无数患者的生命N但临床发现，约1030患者PCI成功后，心肌组织水平无再灌注，即无复流现象N无复流是PCI后死亡和心梗的独立预测因素无复流现象的反思ASKINGINREPLYONNOFLOWFREDERICSR,ETALAMHEARTJ2003145424655可能的机制POSSIBLEMECHANISM可能的机制微血管结构完整性破坏微栓子栓塞白细胞聚集微血管功能完整性损伤，主要是痉挛所致血小板激活氧自由基56策略演变STRATEGICCHANGE回顾再灌注历史过去20年基本上是心外膜冠状动脉再灌注的20年，相信未来的10年将是微循环灌注的10年N检测手段N冠脉微循环灌注评价心肌声学造影成为热点N防治手段N无复流防治腺苷、CAA，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DIABETESCARE29202206,2006CIRCJ2006701099110457一枝独秀三驾马车冠心病治疗观念改变之五FIFTHCHANGEINCONCEPTOFCHDTREATMENT58“药物支架时代”来临THETRENDOFTHEDESTIMESNDES的出现，使心血管介入技术向前迈进了一大步，成为冠心病介入治疗的第3个里程碑。NBMS、冠脉搭桥术以及传统药物治疗是否真的要淡出舞台59STENTINGINCLUDINGDRUGELUTINGSTENTSREDUCESRESTENOSISANDREPEATEDINTERVENTION,BUTDOESNOTREDUCEMORTALITYORMYOCARDIALINFARCTION支架不降低心脏病死率或心梗支架不降低心脏病死率或心梗SERRUYSPW,KUTRYKMJB,ONGATLCORONARYARTERYSTENTSNENGLJMED200635448349560FDA05/12/2006药物支架要求一万例验证三年NFDAHEARTPATIENTSWITHDRUGCOATEDSTENTSFACEBLOODCLOTRISKBYASSOCIATEDPRESSTUESDAY,DECEMBER5,2006WASHINGTONPATIENTSIMPLANTEDWITHDRUGCOATEDSTENTSTOHOLDOPENTHEIRCHOKEDARTERIESFACEASMALLBUTSIGNIFICANTRISKOFBLOODCLOTS,HEALTHOFFICIALSSAIDTUESDAY,ANDANEWSTUDYRECOMMENDEDTHEYTAKECLOTBUSTINGMEDICATIONSINDEFINITELYNGROWINGCONCERNSABOUTTHELONGTERMSAFETYOFDRUGCOATEDSTENTSCOMESTOAHEADTHISWEEK,WHENTHEFOODANDDRUGADMINISTRATIONCONVENESATWODAYMEETINGTODISCUSSCLOTTINGRISKSASSOCIATEDWITHTHEDEVICESNINDOCUMENTSRELEASEDTUESDAY,THEFDASAIDITISUNKNOWNWHETHERTHEREISANINCREASEDRISKOFDEATHORHEARTATTACKINPATIENTSFITTEDWITHTHESOCALLEDDRUGELUTINGSTENTSHOWEVER,THOSEPATIENTSDOFACEANINCREASEDRISKOFBLOODCLOTSAYEARORMOREAFTERSURGERYCOMPAREDWITHTHOSEFITTEDWITHBAREMETALSTENTS,THEAGENCYSAIDINCITINGRECENTSTUDIESNNATICK,MASSBASEDBOSTONSCIENTIFICCORPANDNEWBRUNSWICK,NJBASEDJOHNSONN在美国，只有18的左主干和/或三支病变患者选择支架植入N在欧洲，在复杂病变血运重建中，CABG仍占有主导优势。64关注冠心病HYBRID技术PAYATTENTIONTOHYBRIDTREATMENTN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。65LIFEWIDEOPEN开放生命66危险因素单一控制危险因素复杂干预冠心病治疗观念改变之六SIXTHCHANGEINCONCEPTOFCHDTREATMENT67DIABETESDYSLIPIDEMIAHYPERTENSIONOBESITY68多重危险因素的干预INTERVENTIONSFORMULTIRFN单一危险因素的治疗常可使病人心脑血管病危险下降2030，意味着还有7080的剩余危险需要降低69POLYPILL心脏病一/二级予防POLYPILLAPPROACHFORCLASSICOMPOSITIONSIMVASTATIN40MG,LISINOPRIL,HALFDOSEATENOLOL,LOWDOSEASPIRIN,FOLICACIDBMJ20033261407,1419,1423,1427N目标55岁以上使用,可降低心脑血管事件80TARGETFORTHOSEAGED55ORABOVE,COULDLOWERCARDIOCEREBRALINCIDENCEBY80N争议激烈DISPUTEFIERCENASTRATEGYTOREDUCECARDIOVASCULARDISEASEBYMORETHAN8070CADUET二合一复方已在美作为新药临床应用CADUETCOMBINES2DRUGSIN1TABLETASANEWDRUGHASBEENMARKETEDINTHEUSNCOMPANYPFIZER；络加喜片NREGULATORYSTATUSAPPROVEDBYFDAINJANUARY2004NTREATMENTHBP/ANGINA/HIGHCHOLESTEROLNTABLETSTRENGTHSMGNAMIODIPINENOVASC/ATROVASTATINLIPITOR25/10,20,405/10,20,40,8010/10,20,40,80ASCOTTRIAL,ANGLIOSCANDINAVIANCARDIACOUTCOMETRIALLANCET2005JCIAPRIL1,200571ADVANCE临床试验ADVANCETRIALFURTHERPROGRESSWITHHOPEN欧洲心脏病学会ESC2007年会上ADVANCE研究结果公布纳入20个国家11140例2型糖尿病患者，结果表明43年），与安慰剂组相比，培哚普利2MG吲达帕胺0625MG复方制剂组总死亡、心血管性死亡、冠脉事件、肾脏事件、新发生微蛋白尿的比例均显著降低BY9。N研究结果提示，对血压正常的糖尿病患者，适当的降压治疗是有益的，认为是一种更高效、更科学的“风险控制”治疗策略。JOURNALOFHUMANHYPERTENSION200721,911913LANCET2007370959082984072STENO2临床试验N2型糖尿病患者多为中老年患者，且常合并多重心血管危险因素。STENO2研究平均随访133年的结果发现，与多因素常规治疗组相比，采用多因素强化治疗平均78年组全因死亡、心血管性死亡和复合心血管事件的发生率分别显著降低46、57和59。N该研究提示，应尽早综合强化控制血糖、血压和血脂等指标，以减少心血管事件的发生，多重危险因素强化干预具远期益处。GDEP,ETALNENGLJMEDEFFECTOFAMULTIFACTORIALINTERVENTIONONMORTALITYINTYPE2DIABETESFEB7,200835858059173STENO2临床