1、Percutaneous Coronary Intervention In Diabetic PatientsS.Chiu Wong MD,FACCAssociate Professor of MedicineWeill Medical College of Cornell UniversityDirector,Cardiac Catheterization LaboratoriesThe New York Presbyterian Hospital-Cornell CampusThe ACC Symposium at the Great Wall Meeting,Beijing ChinaO
2、ctober 17,2004PCI in Diabetic Patients Summary Prevalence of Diabetes Mellitus and its Associated Cost?What are the Distinctive Features About Diabetic Vessels?What is the Impact of Drug Eluting Stent in Diabetic Patients with CAD?How could we Optimize PCI Treatment Strategies in Diabetic Patients?P
3、CI in Diabetic Patients Prevalence of Diabetes Mellitus and its Associated Costs?What are the Distinctive Features About Diabetic Vessels?What is the Impact of Drug Eluting Stent in Diabetic Patients with CAD?How Should we Optimize PCI Treatment Strategies in Diabetic Patients?PCI in Diabetic Patien
4、ts Prevalence of Diabetes Mellitus and its Associated Costs?What are the Distinctive Features About Diabetic Vessels?What is the Impact of Drug Eluting Stent in Diabetic Patients with CAD?How Should we Optimize PCI Treatment Strategies in Diabetic Patients?Accessed on Oct 2,2004.www.diabetes.org/dia
5、betes-statistics/national-diabetes-fact-sheet.jspSource:National Diabetes Fact Sheet(American Diabetes Association)National estimates on diabetes in the US in 2002Total:18.2 million people(6.3%of the population)Approximately 90%of patients with diabetes have the type 2 variety which is associated wi
6、th excess body fat and physical inactivity.PCI in Diabetic Patients Prevalence of DM Among US AdultsPCI in Diabetic PatientsDiabetes:A Genetic LegacyApproximately 90%of patients with diabetes have the type 2 variety.The increasing prevalence of type 2 diabetes cannot be divorced from the rising inci
7、dence of obesity and physical inactivity in industrialized society.Both excess body fat and physical inactivity predispose to type 2 diabetes Mokdad,A.H.et al.JAMA 2001;286:1195-1200.PCI in Diabetic Patients Prevalence of DM Among US Adults:1990 vs.2000Incidence of a self-report of diagnosed diabete
8、s increased from 4.9%in 1990 to 7.3%(49%increase)in 2000.Saydah,S.H.et al.JAMA 2004;291:335-342.PCI in Diabetic Patients Percentages of Adults With Recommended Levels of Vascular Disease Risk Factors in NHANES III(1988-1994)and NHANES 1999-2000PCI in Diabetic Patients Levels of HbA1c,blood pressure,
9、and total cholesterol in NHANES Pts Risk factor NHANES 88-94NHANES 99-2000 p Mean HbA1c(%)7.6 7.8 0.30%subjects HbA1c 8.0%36.5 37.2 0.87 Total mean cholesterol(mg/dL)222.8 208.9 200 mg/dL 66.1 51.8 0.001 Total mean systolic BP(mm Hg)137.9 134.8 0.04 Total mean diastolic BP(mm Hg)73.5 71.5 0.12%subje
10、cts with normal BP(SBP 130 and DBP 140 or DBP 90)42.9 40.4 0.56 Saydah SH et al.JAMA 2004;291:335-342.Estimated numbers of people with diabetes by region for 2000 and 2030 and summary of population changesRegion(all ages)#of people with DM in 2000#of people with DM in 2030%change in#of people with D
11、M*%change in total population*%change in population 65*%change in urban population*Established market economies44,26868,15654980N/AFormer socialist economies11,66513,960201442N/AIndia31,70579,44115140168101China20,75742,32110416168115Other Asia and Islands22,32858,1091484219891Sub-Saharan Africa7,14
12、618,64516197147192Latin America and the Caribbean13,30732,9591484019456Middle Eastern Crescent20,05152,7941636719494World171,228366,2121143713461*A positive value indicates an increase,a negative value indicates a decrease.Wild et al Diabetes Care 2004;27:1047-53CountryPeople with diabetes(millions)
13、CountryPeople with diabetes(millions)1India31.7India79.42China20.8China42.33U.S.17.7U.S.30.34Indonesia8.4Indonesia21.35Japan6.8Pakistan13.96Pakistan5.2Brazil11.37Russian Federation4.6Bangladesh11.18Brazil4.6Japan8.99Italy4.3Philippines7.810Bangladesh3.2Egypt6.7PCI in Diabetic Patients Countries with
14、 the highest#of estimated cases of DM for 2000 and 2030“.estimate that there would be 754 thousand new diabetics per year in 25-74 years old Chinese if the total population were 1.3 billion in China in the 21st century”Hu YH,Li GW,Pan XR,Zhonghua Nei Ke Za Zhi.1993 Mar;32(3):173-5.PCI in Patients wi
15、th Diabetes MellitusScope of the ProblemPCI in Diabetic PatientsDiabetes and Cardiovascular ComplicationsUKPDS Investigators Lancet 1998;352:837 Khaw KT et al.Ann Intern Med 2004;141:413-420.PopulationRelative risk 95%CIpMen 1.241.14-1.340.001Women 1.281.06-1.3210yrs were insulin dependent compared
16、to 19%of Diabetics 10yrs(p0.0001)PCI in Patients with Diabetes Mellitus Pre-intervention IVUS Comparison of Insulin-Treated vs Non-Insulin Treated DiabeticsReference LesionInsulin use was the only independent(and negative)predictor of reference segment EEM,and P&M CSA and lesion EEM and P&M CSA.Refe
17、rence SegmentsMintz et al,J Am Coll Cardiol 1995;25:1479-85Nishioka et al.J Am Coll Cardiol 1996;27:1571-76LesionsPCI in Patients with Diabetes Mellitus Remodeling in Acute Coronary SyndromespStableACS0.0080.940.21.060.2Remodeling Index0.00511.14.813.95.5 P&M CSA(mm2)0.31.90.42.31.1 Lumen CSA(mm2)0.
18、00413.04.816.16.2 EEM CSA(mm2)Lesion0.96.23.56.12.6 P&M CSA(mm2)0.067.92.89.13.6 Lumen CSA(mm2)0.214.25.215.25,2 EEM CSA(mm2)Proximal referenceSchoenhagen et al.Circulation 2000;101:598-603PCI in Patients with Diabetes Mellitus Diabetes Modulates Remodeling in ACS and Stable Angina(n=927)DMNo DMAcut
19、e Coronary Syndrome59/183(32.0%)225/469(48.0%)Stable Angina17/88(19.6%)42/187(22.3%)Abizaid,unpublished observationsFrequency of Positive RemodelingPCI in Patients with Diabetes Mellitus Interaction of Diabetes,Vessel Size,Final MLD,and Multiple Stents on Restenosis Post-stentingDiabeticsNon-Diabeti
20、csElezi et al.J Am Coll Cardiol 1997;30:1428-36Elezi et al.J Am Coll Cardiol 1998;32:1866-73PCI in Patients with Diabetes Mellitus IVUS findings in diabetic vs non-diabetic pts in non-stented lesionsWHCOARS EEM CSA(mm2)P&M CSA(mm2)EEM CSA(mm2)P&M CSA(mm2)EEM CSA correlated with P&M in non-diabetics,
21、but not in diabetics indicating that diabetics lacked the ability to respond to the exaggerated intimal hyperplasia that is also presentPCI in Patients with Diabetes Mellitus IVUS Findings in Diabetic vs Nondiabetic Patients Post StentKornowski et al.Circulation 1997;95:1366-9PCI in Patients with Di
22、abetes Mellitus Influence of Diabetes on Early and Late Outcome After PTCAStein et al.Circulation 1995;91:979-989P0.001P0.001P0.001P0.001PCI in Patients with Diabetes Mellitus NHLBI PTCA Registry:Diabetic Patients Kip et al.Circulation 1996;94:1818-1825P0.001P0.001P0.001P0.05PCI in Diabetic Patients
23、Impact of restenosis and disease progression on clinical outcome 14 months after multivessel stentingLoutfi et al.Cath Cardiovasc Intervent 2003;58:451-4PCI in Patients with Diabetes Mellitus Role of vessel size as predictor for in-stent restenosis in diabetic patients Suslbeck et al.Am J Cardiol 20
24、01;88:243-7PCI in Diabetic Patients Summary on Diabetic VesselsDiabetics have more diffuse atherosclerosis and(perhaps)smaller lumen dimensionsIncreased plaque mass especially in non-insulin treated patientsImpaired remodeling responses,especially in insulin-treated patientsDiabetics have increased
25、risk of restenosis post-PCI(both stent or non-stent)Smaller final lumen dimensionsMore intimal hyperplasia in both stent and non-stent interventionsImpaired remodeling responses in non-stent interventionsDiabetics have increased risk of death/MI/PCI of new lesionsIncreased plaque burden?More unstabl
26、e plaque morphologies Small diameter lesions30-40%Long lesions37-50%Diabetes26-46%Ostial lesions40-50%Bifurcated lesions40-60%Source:Kalan Ho,and PCR 2000 market research.Coronary StentsRestenosis Post Stent in Higher Risk Patient/Lesion SubsetsStent is no panaceaPCI in Diabetic Patients Prevalence
27、of Diabetes Mellitus and its Associated Costs?What are the Distinctive Features About Diabetic Vessels?What is the Impact of Drug Eluting Stent in Diabetic Patients with CAD?How Should we Optimize Treatment Strategies Following PCI in Diabetic Patients?Cost-effectiveness(1,000s)can vary dramatically
28、 in patients taking lovastatin for primary prevention.PCI in Diabetic Patients Diabetic Subset in the 4S StudyPyorala K et al.Diabetes Care 1997;20:614-20 PCI in Diabetic Patients SIRIUS:Multivariable Predictors for In-segment Restenosis15mm3.0mm3.43.94.92.5-3.0mm5.66.47.92.5mm8.29.411.5Lesion Lengt
29、h15mm3.0mm7.88.910.92.5-3.0mm12.414.017.02.5mm17.719.823.7Lesion LengthRef DiamRef DiamNonDiabeticDiabetic PCI in Diabetic Patients Studies included in the meta-analysis Dawkins K.ESC Congress 2004;August 28-September 1,2004.StudyOverall patientsDiabetic patientsInsulin-treated patientsTAXUS II slow
30、 release266307TAXUS II moderate release263217TAXUS IV slow release1314318105TAXUS VI moderate release4468935Overall2289458(Controls=242;TAXUS=216)154(Controls=83;TAXUS=71)p=nsp=0.0001p=ns*incl.CABGe-CYPHER:DM Subgroup MACE&TLR 6-month FUN=2716 Pts RAVEL-Diabetic SubgroupSirolimus Control N=19N=25pLe
31、sion length(mm)9.749.42 NSRef.Vessel diameter(mm)2.522.51 NSMLD(mm)Pre0.990.93 NSPost2.372.36 NSFU2.311.56 .0001Late loss(mm)0.080.82 .0001Late loss index 0.050.57 .0001DS(%)FU 16 38 .0001Restenosis rate(%)0 42 .0001TLR-PCI(%)0 32.0 0.007Total MACE(%)10.5 48.0 0.01SIRIUS:Clinical Outcomes in Diabeti
32、c SubgroupSirolimus(n=131)Control(n=148)P-valueLate loss(mm)in-stent0.291.200.001in-segment0.401.000.001Restenosis(%)in-stent8.348.50.001in-segment17.650.50.001TLR(%)6.922.30.001MACE(%)9.225.00.001Lesion length=14.5mm and Reference vessel size=2.75mmAt 9 months 73%p=0.015 83%p 0.0013/3715/555/15828/
33、143New SIRIUS-Diabetic Subgroup 9-month TLRPCI in Diabetic Patients Late loss observed in the meta-analysis Dawkins K.ESC Congress 2004;August 28-September 1,2004Patient subgroupIn-stent late loss(mm)pNondiabetic patients 0.0001Bare-metal stent(n=609)0.86+0.54 Paclitaxel-eluting stent(n=603)0.36+0.4
34、7 Oral-agents-only diabetic patients 0.0001Bare-metal stent(n=79)1.03+0.58 Paclitaxel-eluting stent(n=91)0.36+0.51 Insulin-treated diabetic patients 0.0006Bare-metal stent(n=48)1.01+0.53 Paclitaxel-eluting stent(n=44)0.33+0.50 Review of Drug-eluting Stents in Diabetes:IDDM Patientsn=54n=5142.97.7p=0
35、.007TAXUS IVDIRECTTAXUS IV diabetics*TAXUS:9 month analysis;SIRIUS:8 month analysisControl BMSTAXUS DESCYPHER DESAngiographic restenosis*(mm)706050403020100In segment restenosis rates:insulin-req.diabetic patientsn=3835.0n=140.0DIRECT Diabetic Subgroup Analysis Significant reduction in restenosis co
36、mpared to historicalSIRIUS IDDM patients,attributed to improved operator techniquep=0.03Bx VelocityDIABETes and sirolimus Eluting Stent The DIABETES TrialDIABETES:Background Diabetic patients exhibit a higher incidence of restenosis/MACE after PCI as compared to non-diabetic population.Sirolimus elu
37、ting stents have demonstrated to be effective for the treatment of coronary stenoses of low-to-moderate risk.Subgroup analyses from randomized trials(RAVEL,SIRIUS)have shown a beneficial effect of these stents in diabetic patients.HYPOTHESIS:Sirolimus eluting stent reduces the degree of neointimal h
38、yperplasia after stenting in diabetics.DIABETES Trial:Objective To assess the efficacy of sirolimus eluting stent following successful coronary stent implantation in diabetic patients with de novo coronary stenoses.DIABETES(DIABETes and sirolimus Eluting Stent trial)Multicenter,Prospective,Randomize
39、d.1-Madrid.H.S Carlos(Dr Sabat,PI)2-Barcelona.H.Bellvitge(Dr Gmez-Hospital)3-Valladolid.H.Clnico(Dr Fernndez-Avils)4-Vigo.H do Meixoeiro(Dr Goicolea).2134No official sponsor:grant from Cordis-SpainSpanish Society of Cardiology 2003 grantType of study&Primary Endpoint-Multi(4 German)-center,prospecti
40、ve,randomized(computer),placebo-controlled trial.-Sub-randomization according to the type of diabetes.PRIMARY ENDPOINT:-In-Stent+edges(in-segment)late lumen loss as assessed by QCA at 9-month angiographic follow-up.Secondary Endpoints&Sample sizeSECONDARY ENDPOINTS-Other QCA parameters(restenosis,ML
41、D)at FU.-Mean in-stent+edges neointimal hyperplasia and%volume obstruction by IVUS at 9-month follow-up.-MACE(cardiac death,MI and TLR)at 30 d,9,12 and 24 months.-Development of complications:aneurysm formation,late thrombosis,edge effect,late stent malapposition.SAMPLE SIZE-160 patients(80 SES;80 B
42、MS).(56%difference in late lumen loss:estimated for a LLL of 0.73 mm in BMS to 0.32 mm in SES;SD 0.70,alfa error of 0.05,beta error of 0.10 and 10%missing values).DIABETES:Inclusion criteria Diabetic patient(non-insulin dependent or insulin dependent)according to WHO 1999 Report.Coronary lesions in
43、native coronary arteries and symptoms or objective evidence of ischemia.Lesion favourable for PTCA+stent implantation.Informed consent.DIABETES Trial:Exclusion criteria Diabetic patient without pharmacological treatment(on diet).Stenoses located in true bifurcations,SVG,LIMA or unprotected left main
44、.In-stent restenosis.Chronic renal or hepatic insufficiency.Previous brachytherapy or DES implantation.Recent AMI(72h)with CPK(x 2).Malignancy.901 non-diabetics3 other protocol 147 Exclusion Criteria2 Logistics/Operator80 Patients SES9-month angiographic FU80 Patients BMS163 Patients Eligible1216 Pa
45、tients Undergoing PCI 9-month angiographic FUFailure to cross CTODIABETESSTUDY FLOW CHARTREGISTRY 153 P(48%)(52%Randomized)1-year clinical FU1-year clinical FU1-month clinical FU1-month clinical FU160 Patients RandomizedInclusion CriteriaInformed ConsentRx Centralized(computer)Sub Rx:type of diabete
46、sQCAPrimary End-pointAbciximab+ASA 100-300 mg/day+Clopidogrel 75 mg/day(at least 1 year)Feb 03-Nov 03Flow Chart:160 Pts RandomizationInclusion CriteriaInformed ConsentRx CentralizedSub Rx:type of DM80 pts SES80 pts BMS110 lesions9 Mo Angio FU 102 les(92%)80 pts Cypher111 lesionsDIABETES2 cardiac dea
47、ths8 missing1 cardiac death4 missing9 Mo Angio FU100 les(91%)DIABETESp=NSClinical PresentationSES group(n=80)BMS group(n=80)p=NS45%30%10%5%35%8.8%12.5%30%10%13.7%Location of stenoses11.7%3.6%1.4%20.7%16.7%9.5%14%0.5%9.9%2.7%5.9%0.5%1.8%0.9%Lesion characteristicsReference diameter201030401,02,03,04,0
48、0FrequencyMean:2.34 0.6 mmp=0.082.21 2.262.33 2.352.38 2.40p=NSLesion characteristics*Excluding chronic total occlusionsp=NS for all variables All lesions(n=221)SES(n=111)BMS(n=110)Lesion length*,mm14.58.215.37.6Reference diam,mm 2.330.52.350.5B2/C,n(%)89(80.2)88(80)Calcification,n(%)46(43.4)39(35.8
49、)Total occl,n(%)14(12.6)15(13.6)15.08.12.340.6177(80.1)85(38.5)29(13.1)Studies by lesion length,vessel size and%diabeticsSIRIUS2.802.75 Lesion length(mm)Reference diameter 810121416182022 mm2.55TAXUS IITAXUS IVTAXUS VIRAVELNew SIRIUS2.702.602.502.402.452.352.30mmPACLITAXELRAPAMYCINLESION LENGTHREFER
50、ENCE DIAMETER18%15%24%26%20%23%DIABETES*100%*13%Chronic total occlusionsProcedural Characteristics DIABETESTreated artery,%LAD/LCX/RCA 39/21/40 44/23/33Multivessel stent,%2324Multisegment,%1611N.stenosis/patient1.40.61.40.5N.stent/patient1.60.81.70.9Stent length,mm22102313IIb/IIIa inhibitors,%6454SE
