Drug-Eluting Stents for Multivessel PCI

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SOLACI Chile Congress 2011. Dr.Ajay Kirtane. Drug-Eluting Stents for Multivessel PCI: Indications and Outcomes. Find more presentations on the web site: www.solaci.org/

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Drug-Eluting Stents for Multivessel PCI

  1. 1. Ajay J. Kirtane, MD, SMCenter for Interventional Vascular TherapyColumbia University Medical Center /New York Presbyterian HospitalDrug-Eluting Stents forMultivessel PCI:Indications and Outcomes
  2. 2. Conflict of Interest Disclosure• Ajay J. Kirtane None Off-label use will be discussed
  3. 3. Two Goals of Therapy inPatients with Stable CAD1. Improve Symptoms and Qualityof Life Measured by “soft endpoints”(i.e. angina/QOL scales)2. Improve Prognosis Measured by “hard endpoints”(i.e. death, MI)
  4. 4. It is generally accepted thatrevascularization makes symptomaticpatients feel better… but it is also aFACT that The Presence of Severe CADis Prognostically Important!• Let’s not forget our History… Workload / Exercise Tolerance Burden of Disease / Ischemia Patients with prior MI / DecreasedVentricular Function may haveeven more to gain / or lose
  5. 5. Meta-Analysis of CABG vs. MedicalTherapy: 7 RCTsYusuf S et al, Lancet 1994Mortality
  6. 6. 6.7%3.7%3.3%1.0%2.9%4.8%1.8% 2.0%0%2%4%6%8%10%Medical Rx RevascMitigatated Gradient with Revasuclarization% Total Ischemic Myocardium1- 5% 5-10% 11-20% >20%CardiacDeathRate1331 56 718 109 545 243 252 267P <.0001Hachamovitch et al Circulation. 2003;107:2900-2907.
  7. 7. MPS % Ischemic Myocardium(95% CI) Pre-Rx & 6-18 Months0405101520253530Pre-Rx 6-18m8.2%5.5%(4.7%-6.3%)PCI + OMT (n=159) OMT (n=155)0405101520253530Pre-Rx 6-18m(6.9%-9.4%)8.6% 8.1%Mean = -2.7%(95% CI = -3.8% to -1.7%)Mean = -0.5%(95% CI = -1.6% to 0.6%)p<0.0001Shaw, et al, AHA 2007 and Circulation 2008
  8. 8. • Less progression to decreasedventricular function / ischemiccardiomyopathy• Better tolerance of events in othercoronary distibutions• Altered rheology within target vessel• Less occlusion?Why Could Revascularization of Higher-Risk Ischemic Territories Be Important?
  9. 9. 385 assignedto OMTBARI 2D: Patient Flow378 assignedto CABG807 assignedto OMT798 assignedto PCI2368 pts were enrolled763 were selected forCABG vs. OMT1605 were selected forPCI vs. OMTCoronary angiography inpts with type 2 diabetesIP = insulin provisionIS = insulin sensitizationExclusions:Revasc not indicatedImm. revasc requiredLM diseaseS. Cr. >2.0 mg/dLHgbA1C >13.0%,Cl III or IV HFHepatic dysfunctionPCI or CABG w/i 1 yrA study of prophylactic revascularization among patientswith no “definite need for invasive intervention”The BARI 2D Study Group.NEJM 2009;360:2503-15
  10. 10. BARI 2D: CABG StratumSurvival Freedom from MACE(death, MI, or stroke)Survival(%)YearsEvent-freeSurvival(%)YearsP=0.330 1 2 3 4 5020406080Medical TherapyRevascularization83.686.4N at Risk 763 734 718 692 586 333100P=0.010 1 2 3 4 5020406080Medical TherapyRevascularization69.577.6N at Risk 763 668 634 568 421 230100The BARI 2D Study Group.NEJM 2009;360:2503-15
  11. 11. BARI 2D: Who got Revascularized?PCI Stratum CABG Stratum pN=1176 N=1192USA 73.7% 41.4% <0.0001Prior MI 30.1% 36.0% <0.05Proximal LAD disease 10.3% 19.4% <0.05Pts without prior proceduresN lesions ≥50% DS, mean 2.1 ± 1.5 3.6 ± 1.7 <0.0001N lesions ≥70% DS, mean 0.8 ± 1.0 1.7 ± 1.3 <0.0001N of diseased vessels <0.0001- 0 4% 1%- 1 41% 9%- 2 36% 37%- 3 19% 53%Any total occlusions 7% 14% <0.0001Jeopardy index, % 38 ± 22 61 ± 21 <0.0001The BARI 2D Study Group. NEJM 2009;360:2503-15Schwartz L et al. AJC 2009;103:632–638
  12. 12. Ischemia-Eligible Stable Patient(Stable CAD, Moderate-Severe Ischemia)Blinded Coronary CTAEligible Anatomy?RANDOMIZEInvasive Strategy(Cath withOptimal Revasc + OMT)CT ExclusionAncillary StudyOMT Strategy(OMT Alone)YESNOISCHEMIA Trial Proposed DesignJ. Hochman, TCT 2010
  13. 13. 5-year D/MI/CVA PCI vs. CABG16.7% vs. 16.9%, P=0.69HR [95%CI] = 0.96 [0.79-1.16]DaysFreedomfromDeath,StrokeandMI(%)10090807060500 365 730 1095 1460 1825Daemen J et al. Circulation 2008;118:1146-1154Bare Metal Stents vs. CABGCABG 83.1%PCI 83.3%4 randomized trials, 3,051 randomized pts,5-year follow-up (patient level pooled analysis)PLR = 0.64
  14. 14. Hlatky et al, The Lancet 2009;373:1190-119710 RCTs 7812 Pts: CABG vs. PCI: No Difference inDeath and MICABG 3889 3767 3675 3415 3180 2693 1853 1609 1477PCI 3923 3798 3709 3431 3205 2658 1828 1576 1452Years of follow-upMortality(%)CABGPCI353025201510500 1 2 3 4 5 6 7 8No. of patients* Deathormyocardialinfarction(%)CABG 3695 3369 3269 3001 2763 2294 1501 1269 1161PCI 3725 3419 3310 3023 2797 2267 1491 1253 1150Years of follow-up353025201510500 1 2 3 4 5 6 7 8
  15. 15. CABG vs PCI :Death and Diabetic StatusNumber of patients*CABG no diabetes 3263 3169 3089 2877 2677 2267 1592 1380 1274CABG diabetes 615 587 575 532 498 421 257 225 200PCI no diabetes 3298 3217 3148 2918 2725 2281 1608 1393 1288618 574 555 508 475 373 218 179 160Years of follow-upMortality(%)CABG no diabetesCABG diabetesPCI no diabetesPCI diabetes353025201510500 1 2 3 4 5 6 7 8PCI diabetesHlatky et al, The Lancet 2009;373:1190-1197
  16. 16. 71% enrolled(N=3,075)All Pts with de novo 3VD and/orLM disease (N=4,337)Treatment preference (9.4%)Referring MD or pts. refusedinformed consent (7.0%)Inclusion/exclusion (4.7%)Withdrew before consent (4.3%)Other (1.8%)Medical treatment (1.2%)TAXUSn=903PCIn=198CABGn=1077CABGn=897no f/un=4285yr f/un=649PCIall captured w/follow upCABG2500750 w/ f/uvsTotal enrollmentN=3075Stratification:LM and DiabetesTwo Registry ArmsRandomized Armsn=1800Two Registry ArmsN=1275Randomized ArmsN=1800Heart Team (surgeon & interventionalist)PCIN=198CABGN=1077Amenable for only onetreatment approachTAXUS*N=903CABGN=897vsAmenable for bothtreatment optionsStratification:LM and DiabetesLM33.7%3VD66.3%LM34.6%3VD65.4%23 US Sites62 EU Sites +SYNTAX Trial Design*TAXUS Express
  17. 17. SYNTAX: All-Cause Death to 3 YearsBefore 1 year*3.5% vs 4.4%P=0.37TAXUS (N=903)CABG (N=897)6.7%8.6%0 12 3620400Months Since AllocationCumulativeEventRate(%)1-2 years*1.5% vs 1.9%P=0.532-3 years*1.9% vs 2.6%P=0.3224Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary ratesEvent Rate ± 1.5 SE. * Fisher’s Exact TestP=0.13
  18. 18. SYNTAX: All-Cause Death/CVA/MI to 3 YearsBefore 1 year*7.7% vs 7.6%P=0.98TAXUS (N=903)CABG (N=897)12.0%14.1%0 12 3620400Months Since AllocationCumulativeEventRate(%)1-2 years*2.2% vs 3.5%P=0.112-3 years*2.5% vs 3.8%P=0.1424Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary ratesEvent Rate ± 1.5 SE. * Fisher’s Exact TestP=0.21ITT population
  19. 19. SYNTAX: MACCE to 3 YearsBefore 1 year*12.4% vs 17.8%P<0.002TAXUS (N=903)CABG (N=897)20.2%28.0%0 12 3620400Months Since AllocationCumulativeEventRate(%)1-2 years*5.7% vs 8.3%P=0.032-3 years*4.8% vs 6.7%P=0.1024Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary ratesEvent Rate ± 1.5 SE. * Fisher’s Exact TestP<0.001ITT population
  20. 20. SYNTAX: Repeat Revascularization to 3 YearsBefore 1 year*5.9% vs 13.5%P<0.001TAXUS (N=903)CABG (N=897)10.7%19.7%0 12 3620400Months Since AllocationCumulativeEventRate(%)1-2 years*3.7% vs 5.6%P=0.062-3 years*2.5% vs 3.4%P=0.3324Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary ratesEvent Rate ± 1.5 SE. * Fisher’s Exact TestP<0.001ITT population
  21. 21. SYNTAX: Generic QOL and Utilities0.50.60.70.80.91Baseline 1 month 6 months 12 months304050Baseline 1 month 6 months 12 monthsSF-36 Mental Component SummaryP=0.23 P=0.43303540455055Baseline 1 month 6 months 12 monthsP=0.50 P=0.07P=0.16 P=0.99SF-36 Physical Component SummaryEQ-5D Utilities (US)PCICABG0.50.60.70.80.91Baseline 1 month 6 months 12 months304050Baseline 1 month 6 months 12 monthsSF-36 Mental Component SummaryP<0.001303540455055Baseline 1 month 6 months 12 monthsP<0.001P<0.001SF-EQ-5D Utilities (US)PCICABGPCICABG
  22. 22. SAQ-AF: Angina-Free** Defined as SAQ-AF score = 100SYNTAX · Health Economics/Quality of Life ACC 2009 · Orlando, FL · 3271.6%76.3%0%20%40%60%80%100%1 month 6 months 12 monthsPCI CABGP=NSP=NSP=0.0564.4%61.6%68.5%72.0%
  23. 23. PCI and CABG Post-SYNTAX• Each strategy can have greatoutcomes in appropriatelyselected patients• Hard clinical outcomes(death/MI/CVA) are generally similar• Need to weigh the risk of potentialrepeat procedures with PCI vs. thegreater morbidity of CABG
  24. 24. SYNTAX: One-year MACCE Rates by SiteCABG MACCE (%)TAXUSStentMACCE(%)5030402010010 20 30 40 50Size of circle adjusted for number of patients
  25. 25. MACCE to 3 Years by SYNTAX ScoreTercile Low Scores (0-22)Mean baselineSYNTAX ScoreCABG 16.6 ± 4.0TAXUS 16.7 ± 4.1TAXUS (N=299)CABG (N=275)22.5%22.7%0 12 3620400Months Since AllocationCumulativeEventRate(%)24Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary ratesEvent Rate ± 1.5 SE. * Fisher’s Exact TestP=0.98Calculated by core laboratory;ITT population
  26. 26. MACCE to 3 Years by SYNTAX ScoreTercile Intermediate Scores (23-32)Mean baselineSYNTAX ScoreCABG 27.4 ± 2.8TAXUS 27.3 ± 2.8TAXUS (N=310)CABG (N=300)18.9%27.4%0 12 3620400Months Since AllocationCumulativeEventRate(%)24Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary ratesEvent Rate ± 1.5 SE. * Fisher’s Exact TestP=0.02Calculated by core laboratory;ITT population
  27. 27. MACCE to 3 Years by SYNTAX ScoreTercile High Scores (>33)Mean baselineSYNTAX ScoreCABG 41.5 ± 7.1TAXUS 41.7 ± 7.8TAXUS (N=290)CABG (N=315)19.5%34.1%0 12 3620400Months Since AllocationCumulativeEventRate(%)24Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary ratesEvent Rate ± 1.5 SE. * Fisher’s Exact TestP<0.001Calculated by core laboratory;ITT population
  28. 28. Indications for CABG vs PCI in stable patients withlesions suitable for both procedures and lowpredicted surgical mortalitySubset of CAD by anatomy Favours CABG Favours PCI1VD or 2VD – non proximal LAD IIb C I C1VD or 2VD – proximal LAD I A IIa B3VD simple lesions, full functional revascularizationachievable with PCI, SYNTAX score ≤ 22I A IIa B3VD complex lesions, incomplete revascularizarionachievable with PCI, SYNTAX score > 22I A III ALeft main (isolated or 1VD, ostium/shaft) I A IIa BLeft main (isolated or 1VD, bifurcation) I A IIb BLeft main + 2VD or 3VD, SYNTAX score ≤ 32 I A IIb BLeft main + 2VD or 3VD, SYNTAX score ≥ 33 I A III BESC guidelines 2010
  29. 29. Pitfalls and issues relevant to SYNTAXscore application in clinical practice Time-consuming, with Interobserver and intraobservervariability Does not account for clinical or procedural variablesthat are known to impact outcomes during and after PCI Underpowered outcomes based upon subgroupanalysis Does not include any subset of lesions (i.e. in-stentrestenosis, stenotic bypass grafts, coronary anomalies,muscular bridges, aneurysms) Does not account for patient choice!Capodanno, et al. Am Heart J 2011;161:462-70
  30. 30. In observational registries, the intermediate tertile isfrequently poorly calibrated with respect to theoutcomes of the high and low tertiles32-month MACEBrito et al.EuroPCR 20103-year MACCEMAIN COMPAREJACC Interv 2010SYNTAXCirculation 20101-year MACCE 1-year MACECapodanno et al.Circ Card Interv 2009Expected risk for the intermediate stratum+14.0%-11.2%+6.5%Capodanno, et al. Am Heart J 2011;161:462-70
  31. 31. Mortality with Complete vs.Incomplete Revascularization in MVDCategorization by SYNTAX ScoreKim YH et al, Circulation 2011
  32. 32. FAME: Optimizing CompleteRevascularizationTonino PAL et al. NEJM 2009;360:213–24FFR-guided(n=509)30 days2.9% 90 days3.8% 180 days4.9%360 days5.3%Angio-guided(n=496)Absolute difference in MACE-free survivalDaysFreedomfromdeath,MI,revasc0 60 120 180 240 300 3600.700.750.800.850.900.951.00MACE 13.3% vs. 18.2%P=0.021005 pts with MVD undergoing PCI with DES were randomized toFFR-guided vs. angio-guided intervention
  33. 33. 3056029-1Angiographic vs. FunctionalSeverity of Coronary StenosisOf 509 pts with angiographically-defined MVD,46% had “functional MVD”FFR50-70 71-90 91-99Stenosis classification by angiography~20%~35%Tonino et al, NEJM 2009
  34. 34. FAME : “Downgrading” Multivessel Diseasewith FFR9% 14%43%34%3-VD2-VD1-VD0-VD43%45%12%2-VD1-VD0-VD3 Vessel Disease 2 Vessel DiseaseTonino et al, JACC 2010;55:2816-2186% 3VD and 57% 2VD reclassified >1 vessel
  35. 35. Change in SYNTAX Score after FFR166(34%)170(35%)160(32%)Lowest TertileMiddle TertileHighest TertileCW Nam (preliminary data); presented TCT 2010Without FFRSYNTAX score ~500 FAME patients after FFR281(57%)119(24%)95(19%)Lowest TertileMiddle TertileHighest TertileWith FFR
  36. 36. Stable Patient scheduled for1, 2, or 3-vessel PCIFFR in all stenosesFFR≤0.80 in ≥1 lesionRANDOMIZE (n=1600)PCI + OMT(Indicated stenoses)OMT AloneRegistryOMT AloneYESNOFAME II Study DesignW. Fearon, TCT 2010
  37. 37. SPIRIT II, III, IV and COMPARE trialsPooled database analysis (n=6,789)Ischemic TLRP<0.001HR: 0.60 [0.48, 0.75]EES (n=4,247)PES (n=2,542)4247 4143 4004 33632542 2416 2328 2018Number at riskXIENCETAXUS6.6%IschemicTLR(%)010Time in Months0 3 6 9 12 15 18 21 24389122604.1%5 4.7%2.3%
  38. 38. SPIRIT II, III, IV and COMPARE trialsPooled database analysis (n=6,789)Stent thrombosis (ARC definite/probable)4247 4177 4082 34792542 2463 2408 2110Number at riskXIENCETAXUS2.3%StentthrombosisARCdeforprob(%)0123Time in Months0 3 6 9 12 15 18 21 24399823500.7%p<0.001HR: 0.30 [0.19, 0.47]EES (n=4,247)PES (n=2,542)
  39. 39. Potential SYNTAX MACCE with 2nd Gen DESTAXUS (N=903)CABG (N=897)20.2%28.0%0 12 3620400Months Since AllocationCumulativeEventRate(%)24Cumulative KM Event Rate ± 1.5 SE; log-rank P value; * Binary ratesEvent Rate ± 1.5 SE. * Fisher’s Exact TestP<0.001ITT population30%
  40. 40. Eligibility: DM patients with MV-CAD eligible for stent or surgeryExclude: Patients with acute STEMI, cardiogenic shockMV DES stenting(Cypher or TAXUS)and abciximabCABG with or withoutcardiopulmonarybypassPRIMARY Endpoint: 3-year death, MI, strokeSECONDARY Endpoints: 12-month MACCE, 3-year Quality of LifeN=1900 at 100 centers fromNA, SA, EU, Rand. 1:1PI: Valentin FusterFREEDOM Trial (NHLBI)
  41. 41. Key Decision Points in MultivesselRevascularization• What are the goals of therapy?• Can the patient take/adhere to DAPT?• Is the patient high surgical risk?• Is the patient insulin dependent?• WHAT DOES THE PATIENT WANT?
  42. 42. Conclusions: Multivessel Disease• These are high-risk coronary lesions and theleast stable subtypes of “stable CAD”• PCI and CABG have very similar rates of“hard” clinical endpoints and Sx/QOL willlargely depend on completeness of revasc Greater rates of repeat revascularization with PCI,especially in complex disease• Patient selection and patient preference willgenerally dictate the best and mostappropriate care!

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