1、糖尿病患者冠脉血运重建糖尿病患者冠脉血运重建Aaron Kugelmass,MD,FACCChief of CardiologyDirector,Heart and Vascular CenterBaystate Medical Center/Tufts School of MedicineSpringfield,MA,USA申申 明明 无糖尿病流行状况糖尿病流行状况 全球发病率 20002.8%(171 Million)20304.4%(366 Million)升高36%!在美国，糖尿病患者占血运重建25%以上Stone,et al,Am J Card,2007 延长寿命（生存）改善生活质量
2、（症状）心绞痛 心衰 心律失常 减少再住院等 降低治疗成本（社会经济）冠心病治疗目的冠心病治疗目的Duke 数据:校正后的17年生存曲线MEDCABGPCI血运重建血运重建-Smith PK et al.Ann Thorac Surg 82;2006冠脉狭窄的部位和程度对心血管死亡的影响冠脉狭窄的部位和程度对心血管死亡的影响对29,082 患者（介入治疗和药物治疗）7年随访结果-Duke 数据 心血管死亡风险心血管死亡风险患者人数患者人数02334374248505971768194981000 50%1支支 5074%2或或3支支 5074%1支支 75%2支支 75%;0 95%1支支 9
3、5%Prox.LAD或或 5074%LM2支支 75%;最少最少1支支 95%2支支 75%且且 LAD 95%或或 LM 2549%或或 3支支 75%且且 50%)血栓素血栓素/前列环素合成前列环素合成 活性依赖配体表达活性依赖配体表达GP 2b/3aP 选择素选择素纤维蛋白原纤维蛋白原年轻血小板，血小板聚集能力年轻血小板，血小板聚集能力P2Y1 抵抗抵抗 P2Y1 非依赖通路上调非依赖通路上调 临床表现临床表现:支架内血栓形成支架内血栓形成 ACS再发再发GP 2b/3a 抑制剂使用受益抑制剂使用受益Thienopyridine 抵抗抵抗糖尿病患者伴发血液高凝状态糖尿病患者伴发血液高凝状
4、态 粥样斑块组织因子含量增加粥样斑块组织因子含量增加 tPA降低降低 PAI-1增加增加 纤维蛋白原增加纤维蛋白原增加 当斑块出现裂隙或斑块破裂，更容易发生严重临当斑块出现裂隙或斑块破裂，更容易发生严重临床事件床事件血运重建血运重建 对于糖尿病患者血运重建是否可行？对于糖尿病患者血运重建是否可行？Kip et al.Circulation 1996;94:1818-1825裸支架血运重建裸支架血运重建DM 再狭窄率显著增高术后支架内 MLD病变长度(mm)MLD (mm)10152025糖尿病2.535%39%43%46%3.023%26.530%33%4.015%17%19%22%非糖尿病2
5、.525%27%30%33%3.017%19%22%25%3.510%12%14%16%4.06%7%8%10%Ho,et al,1999药物洗脱支架血运重建药物洗脱支架血运重建 DES 显著降低糖尿病患者支架再狭窄率.然而，相对风险依然存在.Stone,et al,Am J Cardiol,2007冠脉搭桥血运重建生存率冠脉搭桥血运重建生存率 糖尿病患者术后生存率和非糖尿病患者相似BARI 试验 4年随访结果Schwartz,et al,Circulation,2002糖尿病糖尿病-死亡死亡-CABG STS 数据 30天死亡率JACC 2002;40:418-423Diabetes(Med
6、ical Treatment)N=452Non-DiabeticN=1348TAXUSCABG Death/CVA/MIMACCEDeath/CVA/MIMACCEP=0.96P=0.0025P=0.08P=0.97CABG其他其他“问题问题”胸骨切开 卒中/神经系统损伤 恢复期延长 出血风险/输血风险 肾衰竭 纵膈炎 心包切开术后综合症糖尿病患者糖尿病患者CABG vs.PCI:在研中在研中 人群治疗N随访（年)主要终点CARDIA 糖尿病患者，2 支血管病变心血管内外科医生一致认为适合血运重建任意选择 PCI(阿司匹林,氯吡格雷,阿昔单抗，sirolimus洗脱支架 vs 任意选择 CAB
7、G(1 LIMA 桥)600(例)2-5死亡，心肌梗死，脑卒中FREEDOM 适合 PCI 或 CABG，糖尿病患者，2 支血管病变Sirolimus洗脱支架 vs CABG2,400(例)5死亡，心肌梗死，心血管事件糖尿病患者血运重建糖尿病患者血运重建 所有冠心病患者应该强化的药物治理所有冠心病患者应该强化的药物治理 冠脉血运重建（冠脉血运重建（PCI 和和 CABG）是冠心病综合治）是冠心病综合治理的重要组成部分理的重要组成部分 基本认识：血运重建受益随患者心血管危险程度基本认识：血运重建受益随患者心血管危险程度增高而增加，对于复杂冠脉病变，增高而增加，对于复杂冠脉病变，CABG 似乎优似
8、乎优于于PCI 无论采取何种血运重建方法，糖尿病患者效果相无论采取何种血运重建方法，糖尿病患者效果相对较差对较差 糖尿病患者血运重建选择的基本方法同非糖尿病糖尿病患者血运重建选择的基本方法同非糖尿病患者患者Coronary Revascularization in Diabetic PatientsAaron Kugelmass,MD,FACCChief of CardiologyDirector,Heart and Vascular CenterBaystate Medical Center/Tufts School of MedicineSpringfield,MA,USADisclosu
9、res NoneDiabetes Mellitus:An Epidemic World Wide Incidence of DM 20002.8%(171 Million)20304.4%(366 Million)A 36%Increase!Diabetics Receive 25%of Revascularization Procedures in the USStone,et al,Am J Card,2007 Prolong life(mortality benefit)Improve quality of life(symptom benefit)angina CHF arrhythm
10、ias avoid procedures/rehospitalization,etc Reasonable costs(societal benefit)Treatment for CAD:Goals of TherapyDuke Database:Adjusted 17-year SurvivalMEDCABGPCIRevascularization-Smith PK et al.Ann Thorac Surg 82;2006Influence of Severity and Location of Stenosis on Cardiac Death Over a 7-Year Mean F
11、ollow-up in 29,082 Patients Catheterized for CAD at Duke Between 19862000 and Treated Without RevascularizationRelative Chance of Cardiac DeathNumber of Patients0233437424850597176819498100None 50%One 5074%Two or Three 5074%One 75%Two 75%;None 95%One 95%Prox.LAD or 5074%LMTwo 75%;At least one 95%Two
12、 75%with 95%LAD or 2549%LM or three 75%and 50%reduction)Thromboxane/Prostacyclin Synthesis Activation Dependent Ligand ExpressionGP 2b/3aP SelectinFibrinogenPlatelet Turnover-younger,more aggregable plateletsP2Y1 Resistance Up-regulation of P2Y1 independent pathwaysClinical Manifestations include:St
13、ent ThrombosisRecurrent ACSBenefit of GP 2b/3a InhibitorsThienopyridine ResistanceDiabetes Results in a Hypercoaguble State(Soluble Clotting Cascade)Atheroma Contains Increased Tissue Factor Decreased tPA Increased PAI-1 Increased FibrinogenWhen Plaques Fissure or Rupture,They Are More Likely to Res
14、ult in a Major Clinical EventRevascularization Are Revascularization Methods as Durable in Diabetics?Kip et al.Circulation 1996;94:1818-1825Revascularization DurabilityBare Metal StentsDM Have Significantly More RestenosisPost-ProcedureMLDLesion Length(mm)In-Stent MLD(mm)10152025Diabetic2.535%39%43%
15、46%3.023%26.530%33%4.015%17%19%22%Nondiabetics2.525%27%30%33%3.017%19%22%25%3.510%12%14%16%4.06%7%8%10%Ho,et al,1999Revascularization DurabilityDrug Eluting Stents DES significantly reduce restenosis in diabetics.However,a significant hazard still exists.Stone,et al,Am J Cardiol,2007Revascularizatio
16、n DurabilityCABG and Graft Survival Diabetic Bypass Intermediate Graft Survival Appears to be Similar to that of Non-Diabetics4 Year Graft Survival in the BARI TrialSchwartz,et al,Circulation,2002Diabetes,Mortality and CABGSTS Database 30 Day MortalityJACC 2002;40:418-423Diabetes(Medical Treatment)N
17、=452Non-DiabeticN=1348TAXUSCABG Death/CVA/MIMACCEDeath/CVA/MIMACCEP=0.96P=0.0025P=0.08P=0.97Other CABG“Issues”Sternotomy Stroke/Neurologic Injury Prolonged Recovery Bleeding Risk/Transfusion Risk Renal Failure Mediastinitis Post Pericardiotomy SyndromeCABG vs.PCI in DM:Ongoing Trials PopulationTreat
18、mentNFollow-up(years)Primary EndpointCARDIA Diabetes with 2 vessel CADConsensus by cardiologist and surgeon that patient is suitable for revascularizationOptional PCI(aspirin,clopidogrel,abciximab and sirolimus-eluting stents vs optional CABG(1 actual graft with LIMA to CAD)600(proj.)2-5 yearsDeath,
19、MI,strokeFREEDOM Diabetes with 2 vessel CAD suitable for PCI or CABGPCI with sirolimus-eluting stents vs CABG2,400(proj.)5 yearsDeath,MI,CVACoronary Revascularization Among Diabetics All CAD patients deserve intensive medical Rx Coronary revascularization with PCI and CABG are important components o
20、f an integrated treatment paradigm for all patients CAD.Fundamental tenet in revascularization is that overall benefit increases with patient risk and CABG seems preferred(over PCI)with CAD and CAD complexity Diabetes associated with worse outcomes regardless of revascularization type Fundamentals of revascularization choices seem consistent among diabetic patients
