1、AS发生必备因素:LDL和单核/巨噬细胞(Nature 2008)(Nature 2008)动脉粥样硬化发生机制:2008Nature 2008外膜稳定型斑块(病变)纤维帽(平滑肌细胞和基质)脂质核内皮细胞内膜平滑肌细胞(修复型)中层平滑肌细胞(可伸缩型)外膜lipid core脂质核不稳定型斑块(病变)发生在破裂/侵蚀口的血小板凝聚 斑块破裂血小板粘附血小板激活血栓部分堵塞动脉引起不稳定心绞痛微血栓引起NSTEMI血栓完全堵塞动脉引起STEMIACS发病机制Adapted from Davies MJ.Circulation.1990;82(supl II):30-46.Impaired F
2、ibrinolysisFibrinogenDiabetesMellitusCholesterolSmokingCap FatigueAtheromatous Core(size/consistency)Cap InflammationSystemic FactorsLocal FactorsHomocysteinePlaqueRuptureFuster V,et al.N Engl J Med.1992;326:310-318.Falk E,et al.Circulation.1995:92:657-671.Cap Thickness/Consistency血管完全闭塞心肌酶谱CK-MB or
3、 TroponinTroponin elevated or not 非ST段持续抬高的急性冠脉综合征ST段持续抬高的急性冠脉综合征血管未完全闭塞不稳定心绞痛,非ST段抬高心梗ST段抬高心梗心电图血管腔诊断预后严重性死亡/猝死进展为ST段抬高心梗隐性冠心病 无症状心肌缺血 缺血性心肌病稳定性心绞痛 不稳定性心绞痛 变异型心绞痛劳力型心绞痛 (1)稳定劳力型心绞痛 (2)初发劳力型心绞痛 (3)恶化劳力型心绞痛 (4)卧位型心绞痛自发型心绞痛 (1)单纯自发型心绞痛 (2)变异型心绞痛混合型心绞痛梗死后心绞痛1.初发心绞痛:病程在1个月内新发生的心绞痛。可表现为自发性与劳力性发作并存,疼痛分级在I
4、II级以上2.恶化劳力型心绞痛:既往有心绞痛史,近1个月内心绞痛恶化加重,发作次数频繁,时间延长或痛阈降低(即加拿大劳力型心绞痛分级CCS I-IV至少增加1级,或至少达到III级)3.静息心绞痛:心绞痛发生在休息或安静状态,发作持续时间通常在20分钟以上4.梗死后心绞痛:指急性心肌梗死发病24小时后至1个月内发生的心绞痛5.变异型心绞痛:休息或一般活动时发生的心绞痛,发作时心电图显示ST段一过性抬高,多数自行缓解。多数不演变为心肌梗死,但少数可演变为心肌梗死。不稳定性心绞痛的主要表现组 别 加拿大心脏病学会 运动试验指标 发作时心电图 心绞痛分类(IIV)(Bruce 或 MET方法)低危险
5、组 I、II III级或 6METS以上 ST段压低1mm中危险组 II、III 低于III级或6METS 心率130次 ST段压低1mm高危险组 III、IV 低于II级或4METS 心率130次 ST段压低1mmSensitivity and Specificity of Stress ImagingModality Total Patients Sensitivity SpecificityExercise SPECT 5272 0.88 0.72Adenosine SPECT 2137 0.90 0.82Exercise Echo 2788 0.85 0.81Dobutamine Ec
6、ho 2582 0.81 0.79Data from Gibbons RJ,et al.ACC/AHA 2002 guideline update for the management of patients with chronic stable angina冠状动脉CTAMark DB,Berman DS,Budoff MJ,et al.Circulation.2010;121(22):2509-43.2010年ACCF/ACR/AHA/NASCI/SAIP/SCAI/SCCT联合公布了冠脉CT血管造影(CTA)专家共识与冠状动脉造影对照,CTA诊断的敏感性和特异性Revasculariz
7、ation in Patients with Multivessel DiseaseCABGPCITripl-vessel diseaseLV dysfuncitionLMCA disease Diffuse diseaseDouble-vessel diseasePreserved LV functionSuitable anatomyAdvanced age“Salvage”procedureDiabetics?Indications for coronary revascularization with CABG or PCI in patients with multivessel d
8、iseaseu 稳定型劳力性心绞痛u 既往已明确的冠状动脉病变经治疗后症状消失、需定期随访的稳定患者(低危的不稳定型心绞痛、变异型心绞痛、微血管性心绞痛)u 有创或无创检查提示有无症状缺血性心脏病患者(如以呼吸困难等心力衰竭症状起病的缺血性心肌 病患者)药物治疗目的:1.预防心肌梗死和猝死,改善生存 2.减轻症状和缺血发作,改善生活质量1.金属裸支架 vs 优化药物治疗2.金属裸支架、药物洗脱支架vs 优化药物治疗3.CABG vs 优化药物治疗Boden WE et al.Am Heart J.2006;151:1173-9.Boden WE et al.N Engl J Med.2007;
9、356:1503-16.Optimal medical therapy*+PCI(n=1149)Optimal medical therapy(n=1138)AHA/ACC Class I/II indications for PCI,suitable coronary artery anatomy+70%stenosis in 1 proximal epicardial vessel+objective evidence of ischemia(or 80%stenosis+CCS class III angina without provocation testing)Primary ou
10、tcomes:All-cause mortality,nonfatal MIFollow-up:Median 4.6 yearsRandomized*Intensive pharmacologic therapy+lifestyle interventionCCS=Canadian Cardiovascular SocietySecondary outcomes:Death,MI,stroke;ACS hospitalizationCOURAGE:Study designHR 1.05(0.87-1.27)P=0.62*Boden WE et al.N Engl J Med.2007;356:
11、1503-16.All-cause death,MI(time to first event)*UnadjustedNo.at riskMedical therapy1138101795983463840819230PCI1149101395283363741720035Medical therapy PCI+medical therapySurvival free of primaryoutcome024700.50.60.70.81.00.9Years6531N Engl J Med 2007;356:150316N Engl J Med 2007;356:150316010300jt-o
12、s.ppt-On-screen 79Glenn N.Levine,et al.JACC Vol.58,No.24,2011.Hermiller JB at TCT 20112.金属裸支架、药物洗脱支架vs 优化药物治疗010300jt-os.ppt-On-screen 83From TCT 2006010300jt-os.ppt-On-screen 84010300jt-os.ppt-On-screen 85XIENCE VN=2458TAXUSN=1229Stent thrombosis(%)0.42%1.23%Stent Thrombosis(ARC Def or Prob)Early(0
13、 30 days)Late(30 days 1 year)Very Late(1 year)Rates(%)are Kaplan-Meier estimates.Stone G,TCT 2010Serruys P,Euro-PCR 2010Serruys P,Euro-PCR 2010n2012年 Lacet 一项关于药物洗脱支架和金属裸支架支架内血栓形成的对比研究meta分析,纳入49个临床试验50844例名患者;nCoCr-EES组一年明确的支架内血栓发生率显著低于BMS组(OR 0.23,95%CI 0.13-0.41),两组的差异在随访30天内和31天-1年内同样显著(OR 0.21,
14、95%CI 0.11-0.42;OR 0.27,95%CI 0.08-0.74)。n同时,同时,CoCr-EESCoCr-EES组一年内明确的支架内血栓发生率较组一年内明确的支架内血栓发生率较PESPES组、组、SESSES组、组、ZESZES组和组和Resolute ZESResolute ZES组均低。组均低。n随访至2年,CoCr-EES组明确的支架内血栓发生率仍然低于BMS组和PES组(OR 0.35,95%CI 0.17-0.69;OR 0.34,95%CI 0.19-0.62),而其他的药物洗脱支架较BMS,在2年随访期内并未显示出更低的明确支架内血栓发生率。Tullio Palm
15、erini et al.Lancet 2012;379:1393402DES vs BMS DES vs BMS 支架内血栓?支架内血栓?CoCr-EES组 vs BMS组的差异在随访30天和31天-1年内同样显著OR 0.21,95%CI 0.11-0.42OR 0.27,95%CI 0.08-0.74)Tullio Palmerini et al.Lancet 2012;379:1393402DES vs BMS DES vs BMS 支架内血栓?支架内血栓?n2014年Windecker等发表一项大型的网络meta分析n纳入93553名来自100个临床试验的患者,终点:全因死亡、再次血运
16、重建uPTCA、金属裸支架、第一代药物洗脱支架不能显著减低死亡率,而新型的药物洗脱支架则有了质变:PTCA 0.85,0.68 to 1.04PES 0.92,0.75 to 1.12SES 0.91,0.75 to 1.10 ZES(Endeavor)0.88,0.69 to 1.10u新一代药物洗脱支架较单纯药物治疗降低死亡率:EES 0.75,0.59 to 0.96ZES(Resolute)0.65,0.42 to 1.00Stephan Windecker et al.BMJ 2014;348:g3859010300jt-os.ppt-On-screen 933.CABG vs 优化
17、药物治疗Yusuf S,Zucker D,et al.Lancet 1994,344:563-70.Stephan Windecker et al.BMJ 2014;348:g3859Revascularisation versus medical treatment in patients with stable coronary artery disease:network meta-analysis Stephan Windecker et al.BMJ 2014;348:g3859962.随访结果随访终点随访终点PCIPCICABGCABGMTMT22P P值值(n=1313n=131
18、3)(n=1259n=1259)(n=863n=863)1 1年年MACCEMACCE7070(5.3%5.3%)4040(3.2%3.2%)7979(9.2%9.2%)34.03 34.03 0.001 0.0011 1年全因死亡年全因死亡8 8(0.6%0.6%)1414(1.1%1.1%)2929(3.4%3.4%)25.46 25.46 0.001 0.0011 1年心肌梗死年心肌梗死9 9(0.7%0.7%)1 1(0.1%0.1%)1515(1.7%1.7%)20.75 20.75 0.001 0.0011 1年再次血运重建年再次血运重建5555(4.2%4.2%)1111(0.9
19、%0.9%)3838(4.4%4.4%)37.79 37.79 0.001 0.0011 1年卒中年卒中6 6(0.5%0.5%)1414(1.1%1.1%)6 6(0.7%0.7%)3.72 3.72 0.1550.1552 2年年MACCEMACCE118118(9.0%9.0%)6565(5.2%5.2%)131131(15.2%15.2%)60.30 60.30 0.001 0.0012 2年全因死亡年全因死亡1414(1.1%1.1%)1919(1.5%1.5%)6363(7.3%7.3%)73.03 73.03 0.001 0.0012 2年心肌梗死年心肌梗死2020(1.5%1.
20、5%)4 4(0.3%0.3%)1717(2.0%2.0%)16.36 16.36 0.001 0.0012 2年再次血运重建年再次血运重建8989(6.8%6.8%)1818(1.4%1.4%)4646(5.3%5.3%)52.36 52.36 0.001 0.0012 2年卒中年卒中1313(1.0%1.0%)2626(2.1%2.1%)1616(1.9%1.9%)5.51 5.51 0.0640.064971年随访 Kaplan-Meie生存曲线全全 因因 死死 亡亡%Log-rank P 0.001Log-rank P 0.001MACCE%MACCE%Log-rank P 0.001
21、Log-rank P 0.001心心 肌肌 梗梗 死死%Log-rank P 0.001Log-rank P 0.001再再 次次 血血 运运 重重 建建%Log-rank P 0.001Log-rank P 0.001卒卒 中中%Log-rank P 0.001Log-rank P 0.001983.2年随访 Kaplan-Meier生存曲线全全 因因 死死 亡亡%Log-rank P 0.001Log-rank P 0.001MACCE%MACCE%Log-rank P 0.001Log-rank P 0.001心心 肌肌 梗梗 死死%Log-rank P 0.001Log-rank P
22、0.001再再 次次 血血 运运 重重 建建%Log-rank Log-rank P P 0.001 0.001卒卒 中中%Log-rank P 0.001Log-rank P 0.001994.多因素Cox比例风险回归分析CABG vs.PCI1年随访2年随访HR(95%CI)P值HR(95%CI)P值MACCE0.51(0.33,0.77)0.0010.49(0.36,0.68)0.001全因死亡1.21(0.48,3.00)0.690.95(0.47,1.96)0.897心肌梗死0.09(0.01,0.76)0.0270.19(0.06,0.59)0.004再次血运重建0.21(0.10
23、,0.41)0.0010.22(0.13,0.37)0.001卒中2.31(0.82,6.47)0.1122.20(1.06,4.55)0.034校正的多因素包括:年龄、性别、BMI、高脂血症、糖尿病、冠心病家族史、卒中史、既往PCI史、既往CABG史、陈旧心梗史、外周血管病史、左室射血分数、心率、术前SNYTAX积分、丙氨酸氨基转移酶、血红蛋白、血肌酐、血尿酸、甘油三酯、高密度脂蛋白胆固醇1004.多因素Cox比例风险回归分析CABG vs.药物1年随访2年随访HR(95%CI)P值HR(95%CI)P值MACCE0.33(0.22,0.49)0.0010.31(0.23,0.42)0.00
24、1全因死亡0.36(0.18,0.70)0.0030.21(0.13,0.37)0.001心肌梗死0.06(0.01,0.48)0.0080.19(0.06,0.60)0.004再次血运重建0.17(0.09,0.34)0.0010.24(0.13,0.41)0.001卒中1.87(0.67,5.24)0.2351.13(0.57,2.21)0.733PCI vs.药物1年随访2年随访HR(95%CI)P值HR(95%CI)P值MACCE0.65(0.45,0.94)0.0210.63(0.47,0.83)0.001全因死亡0.30(0.13,0.69)0.0050.22(0.12,0.42)
25、3232):):PCIPCI组组1212个月缺血事件个月缺血事件增加增加,有有统计学差异统计学差异Serruys PW,et al.N Engl J Med.2009.360(10):961-72.:TAXUS*(N=903)-:CABG(N=897);CABGPCIP valueDeath8.7%9.0%0.92CVA3.9%1.2%0.12MI4.9%8.2%0.27Death,CVA or MI14.8%15.8%0.84Revasc.11.6%21.2%0.02P P=0.27=0.273-vessel Disease3-vessel DiseaseTAXUSTAXUS (N=181)
26、(N=181)CABGCABG (N=171)(N=171)30.4%30.4%24.7%24.7%Site-reported Data;ITT populationSite-reported Data;ITT populationCumulative KM Event Rate Cumulative KM Event Rate 1.5 SE;log-rank 1.5 SE;log-rank P P value valueMonths Since AllocationMonths Since AllocationCumulative Event Rate(%)Cumulative Event
27、Rate(%)0122450500 025254836 4年随访结果得出同样结论SYNTAX评分低危组(评分低危组(0-22)4年随访结果得出同样结论SYNTAX评分中危组(评分中危组(23-32)CABGPCIP valueDeath9.3%11.1%0.49CVA3.6%2.0%0.25MI3.6%9.0%0.009Death,CVA or MI14.9%17.3%0.44Revasc.10.9%20.7%0.002P P=0.006=0.006OverallOverallTAXUSTAXUS (N=310)(N=310)CABGCABG (N=300)(N=300)32.0%32.0%2
28、1.5%21.5%Months Since AllocationMonths Since AllocationCumulative Event Rate(%)Cumulative Event Rate(%)0122450500 025254836Site-reported Data;ITT populationSite-reported Data;ITT populationCumulative KM Event Rate Cumulative KM Event Rate 1.5 SE;log-rank 1.5 SE;log-rank P P value value Cumulative Ev
29、ent Rate(%)Cumulative Event Rate(%)50500 02525012244836Months Since AllocationMonths Since Allocation4年随访结果得出同样结论SYNTAX评分高危组(评分高危组(32)TAXUSTAXUS (N=310)(N=310)CABGCABG (N=300)(N=300)OverallOverallP P0.0010.00140.1%40.1%23.6%23.6%Months Since AllocationMonths Since AllocationCumulative Event Rate(%)C
30、umulative Event Rate(%)0122450500 025254836Site-reported Data;ITT populationSite-reported Data;ITT populationCumulative KM Event Rate Cumulative KM Event Rate 1.5 SE;log-rank 1.5 SE;log-rank P P value valueCABGPCIP valueDeath8.4%16.1%0.004CVA3.7%3.5%0.80MI3.9%9.3%0.01Death,CVA or MI14.6%22.7%0.01Rev
31、asc.11.4%28.8%0.001 32)I,BIII,BI,AIII,B三支血管病变(SYNTAX评分22)I,AI,BI,AIIa,B三支血管病变(SYNTAX评分 23-32)I,AIII,BI,AIII,A三支血管病变(SYNTAX评分 32)I,AIII,BI,AIII,A与2010版指南相比,新指南对SCAD推荐的改变:对左前降支近端病变、简单的左主干病变(SYNTAX评分22;)、简单的三支血管病变(SYNTAX评分22)及复杂左主干病变(SYNTAX评分32),PCI的推荐等级被下调1.European Heart Journal(2010)31,250125552.Eur
32、opean Heart Journal.doi:10.1093/eurheartj/ehu2782018血运重建指南对于SCAD血运重建策略的推荐SCAD严重程度严重程度2018推荐推荐2014推荐推荐CABGPCICABGPCI一支或两只病变,无左前降支近端狭窄一支或两只病变,无左前降支近端狭窄IIb,C I,CIIb,C I,C一支病变,左前近端狭窄一支病变,左前近端狭窄I,AI,AI,AI,A两支病变,左前近端狭窄两支病变,左前近端狭窄I,BI,CI,BI,C左主干病变,左主干病变,SYNTAX评分评分22I,AI,AI,BI,B左主干病变,左主干病变,SYNTAX评分评分23-32I,
33、AIIa,AI,BIIa,B左主干病变,左主干病变,SYNTAX评分评分33I,AIII,BI,BIII,B三支病变,三支病变,SYNTAX评分评分22,不合并糖尿病,不合并糖尿病I,AI,AI,AI,B三支病变,三支病变,SYNTAX评分评分22,合并糖尿病,合并糖尿病I,AIIb,A三支病变,三支病变,SYNTAX评分评分22,不合并糖尿病,不合并糖尿病I,AIII,AI,AIII,B三支病变,三支病变,SYNTAX评分评分22,合并糖尿病,合并糖尿病I,AIII,A-对于三支病变,对于三支病变,SYNTAX评分评分22,并合并糖尿病患者,并合并糖尿病患者,PCI推荐等级被下调推荐等级被下
34、调推荐推荐等级证据水平外科手术风险评估推荐使用STS评分计算CABG术后住院期间或30天内死亡率和住院期间发病率B可考虑使用EuroSCORE 评分计算CABG术后住院期间死亡率bBCAD复杂性评估对于LM或多支病变患者,推荐使用SYNTAX评分计算CAD的解剖复杂程度以及PCI后的长期死亡率和发病率B在考虑选择PCI还是CABG时,应优先考虑血运重建的完全程度aBEuroSCOREEuroSCORE=欧洲心脏手术风险评估系统;欧洲心脏手术风险评估系统;CABG=CABG=冠状动脉旁路移植术;冠状动脉旁路移植术;CAD=CAD=冠状动脉;冠状动脉;LM=LM=左主左主干;干;PCI=PCI=经
35、皮冠状动脉介入治疗;经皮冠状动脉介入治疗;STS=STS=胸外科协胸外科协会会新增2018 ESC/EACTS Guidelines onmyocardial revascularization.European Heart Journal(2018)00,1-96.降级2018年ESC心肌血运重建指南推荐升级2017年ACC/AHA稳定冠心病血运重建指南推荐010300jt-os.ppt-On-screen 117Supported by NHLBI U01 grant#01HLO71988 This work is solely the responsibility of the auth
36、ors Introduction To The FREEDOM TrialRevascularization for patients with multivessel coronary disease MVCD-is performed commonly throughout the world,and over 25-30%of such patients have diabetes.In the BARI trial,the subgroup of diabetics with MVCD who underwent CABG lived longer than those with PC
37、I.The FREEDOM trial is the largest prospective study in diabetics with MVCD intensively treated medically,and seeking to discover the best revascularization approach FREEDOM研究研究(the future revascularization evaluation in patients with diabetes mellitus:optimal management of multivessel disease)n入选19
38、00例冠心病合并糖尿病患者(血管造影证实存在2支或以上的主要冠状动脉血管病变),SYNTAX评分中位数26,低危、中危和高危患者的比例分别占35%、45%、20%。n除外标准包括:严重心力衰竭、6个月内的卒中或严重卒中、2支以上血管为完全闭塞病变、左主干病变、急性心肌梗死。n平均随访3.8年。Michael E.Farkouh,et al.N Engl J Med 2012,367:2375-84.All concomitant Meds shown to be beneficial were encouraged,including:clopidogrel,ACE inhib.,ARBs,b
39、-blockers,statins3020100Death/Stroke/MI,%PCI/DESLogrank P=0.005CABGPCI/DESCABG5-Year Event Rates:26.6%vs.18.7%0123456Years post-randomizationPCI/DES N953848788 625 416 219 40 CABG N 943814758 613 422 221 44 PRIMARY OUTCOME DEATH/STROKE/MIMYOCARDIAL INFARCTIONYears post-randomization0123450102030Myoc
40、ardial Infarction,%PCI/DESCABGCABGPCI/DES953853798636422220PCI/DES N947824772629432229Logrank P 4 55%27%Rankin 1 70%60%01020300123456789101112Months post-procedureRepeat Revascularization,%CABGPCI/DES944887856818792PCI/DES N911858836825806 CABG NLog rank P0.000113%5%PCI/DESCABGREPEAT REVASCULARIZATI
41、ON MACCE(DEATH/STROKE/MI/REPEAT REV.)01020300123456789101112Months post-procedureMACCE,%PCI/DESCABG944873842803773PCI/DES N911825805794773 CABG NLogrank P=0.00417%12%PCI/DESCABGFREEDOM研究研究在亚组分析中,无论按性别、SYNTAX评分以及2支或3支病变分组,均显示CABG优于PCI。该试验的缺陷在于非双盲研究,不同中心提供病例的研究者和各中心的PCI、CABG标准及经验差异较大。Michael E.Farkouh
42、,et al.N Engl J Med 2012,367:2375-84.对糖尿病患者血运重建的推荐2014年推荐2012年推荐存在STEMI的患者,如果能在推荐时间内进行直接PCI,推荐行直接PCI优于溶栓I,AI,A存在NSTE-ACS的患者,推荐早起侵入性治疗优于非侵入性治疗I,A存在多支冠脉血管病变和/或缺血证据的稳定性冠心病患者,推荐血管重建以降低心脏不良事件I,BI,A存在多支冠脉血管病变的稳定性冠心病患者,如果手术风险在可接受的范围内,推荐CABG而非PCII,AIIa,B存在多支冠脉血管病变且SYNTAX评分22的稳定性冠心病患者,应考虑PCI替代CABGIIa,BIIa,B推荐新一代药物洗脱支架(DES)优于裸金属支架(BMS)I,AI,A应考虑双侧乳动脉移植术IIa,B正在接受二甲双胍治疗者,冠脉造影/PCI术后2-3天应监测肾功能I,CI,C基于FREEDOM试验结果,新指南提升了手术风险在可接受范围内、伴有多支血管病变的糖尿病患者行CABG手术的推荐级别1.European Heart Journal(2010)31,250125552.European Heart Journal.doi:10.1093/eurheartj/ehu278