Diabetes Mellitus and multivessel disease- Part ii

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  • Diabetes is a landmark trial from Spain by Dr.Manel Sabate in which (100%) 80pts with diabetes were treated with Cypher and there was remarkable reduction in TLR MACE Instent LL and Insegment RR.TLR was only 7.5%,MACE only11.3%,LL only0.08 and RR 0nly 7.7%.
  • Diabetes Mellitus and multivessel disease- Part ii

    1. 1. Diabetes And Multivessel Disease Dr. Dev Pahlajani MD,FACC,FSCAIChief of Interventional Cardiology, Breach Candy Hospital, Mumbai
    2. 2. Type 2 diabetes, 1997–2010 100 Type 2 diabetes in 1997 100 Increase in Type 2 diabetes,1997–2010 80 80Prevalence (millions) Growth rate (%) 60 60 40 40 20 20 0 0 www.cardiositeindia.com Amos AF et al. Diabet Med 1997;14:S1
    3. 3. Why PCI is not well tolerated by Diabetics? General endothelial disease Restenosis Involvement of multiple organs, Kidneys, brain, PVD, eyes Micro circulation, small, long, multiple, diffuse lesions Accelerated atherosclerosis Thrombogenic factors in blood Thrombotic occlusion of stents Diabetic cardiomyopathy www.cardiositeindia.com
    4. 4. Effect of DM on Formation of Coronary Collateral 410 pts 205 Non DM 205 DM Mean ves diam 1.42 0.65 p = 0.05 1.58 0.68 Mean Rentrop collateral score : DM 2.41 2.20 Non DM 2.6 2.39 p = 0.034 “Poorer Collaterals in DM www.cardiositeindia.com Abaciel et al Circ 1999, 99, 2239
    5. 5. Which Diabetes may be considered for multivessel PCI ? Comorbid condition not suitable for surgery Preferably localised lesions RVD > 2.75 mm Redo Sx – High risk for Sx Good Glycemic control HbA1C < 7.0 No contraindication for long term dual antiplatelet therapy DM ON INSULIN THERAPY -CABG www.cardiositeindia.com
    6. 6. DIABETES STUDY www.cardiositeindia.com
    7. 7. DIABETES Study: First Randomised Independent CYPHER Stent Trial in Diabetic Patients• CYPHER Stent vs BMS in de novo coronary lesions in 160 diabetic patients• Small diameter lesions treated – Reference vessel diameter 2.34mm, lesion length 15mm• Significantly smaller vessels treated in the IDDM group – 2.21mm in the CYPHER Stent arm www.cardiositeindia.com Sabaté M. DIABETES Study results presented at TCT 2004
    8. 8. ISAR-DIABETES – Late Loss (6m)Late Lumen Loss (In-Segment) Late Lumen Loss (In-Stent) CYPHER TAXUS CYPHER TAXUS 0.8 0.8 p=0.02 p<0.001 36% 0.67 0.6 0.6 58% 0.45 0.43 (mm) (mm) 0.4 0.4 0.19 0.2 0.2 0.0 0.0 Significantly greater reduction in neo intimal hyperplasia, as measured by late loss www.cardiositeindia.com Kastrati A. Presented at ACC 2005
    9. 9. DIABETES Study: QCA Follow Up (9m)In-Stent Late Loss (9m) In-Stent Restenosis (9m) 1.0 40 p<0.0001 p<0.0001 0.8 31.0 87% 0.67 30 84% 0.6 (mm) (%) 20 0.4 10 0.2 4.9 0.09 0 0 CYPHER BMS CYPHER BMS Significantly reduced late loss and restenosis vs BMS in diabetic patients www.cardiositeindia.com Sabaté M. DIABETES Study results presented at TCT 2004 and ACC 2005
    10. 10. DIABETES Study: TLR and MACE (12m)TLR MACE 40 p<0.0001 40 p<0.0001 38.8 35 30 30 71% 79% (%) (%) 20 20 11.3 10 10 7.5 0 0 CYPHER BMS CYPHER BMS Dramatic TLR and MACE reductions No late stent thromboses occurred during the 12-month follow up www.cardiositeindia.com Sabaté M. DIABETES Study results presented at ACC 2005
    11. 11. CYPHER Stent Superiority in DiabetesConfirmed in Long Lesion Registry CYPHER TAXUS Control 60 52.7 50 In-segment Restenosis (%) 40 37.1 p=0.033 p=0.001 30 58% 23.5 69% 20.2 20 10 9.9 6.3 0 n=81 n=51 n=55 n=190 n=99 n=105 Diabetic patients Non-diabetic patients Significantly superior reduction in restenosis rates in patients with diabetes and long lesions (>32mm) www.cardiositeindia.com Park SJ. Presented at TCT 2004
    12. 12. DIABETES Study: TLR and Diabetes Status (12m) BMS CYPHER p=0.001 50 40.7 p=0.009 40 90% 80% 32.1 30% 20 10 7.4 7.7 7.7 0 n=53 n=54 n=26 n=27 NIDDM IDDM Reduction in TLR in insulin-dependent patients comparable with those taking oral agents www.cardiositeindia.com Sabaté M. DIABETES Study results presented at ACC 2005
    13. 13. DIABETES Trial40%35% P < .0001 40% 36% 31.3% P < .000130% 76% 30% 69%25%20% 20%15% 11.3%10% 7.5% 10% 5% 0% 0% Sirolimus Stent Bare Metal Stent Sirolimus Stent Bare Metal Stent TLR MACECONCLUSIONS 9 month clinical follow-up• CYPHER Stent highly significantly reduces TLR , overall MACE,Late Loss and Restenosis in diabetic patients at high risk for restenosis0.8 40%0.7 0.66 33%0.6 88% 30% 76%0.50.4 20%0.30.2 10% 7.7% 0.080.1 0 0% Sirolimus Stent Bare Metal Stent Sirolimus Stent Bare Metal Stent www.cardiositeindia.com Source: Sabate, TCT 2004 In-Stent Late Loss In-Segment Restenosis
    14. 14. Diabetes Trial0.70.6 In-stent Late Loss P < .0001 for all groups0.50.4 82% 92% 82%0.30.20.1 0 Overall Oral IDDM www.cardiositeindia.com
    15. 15. DIABETES TRIALCONCLUSION CYPHER stent as effective in IDDM as in non insulin requiring patients www.cardiositeindia.com
    16. 16. CARDIA TRIAL www.cardiositeindia.com
    17. 17. Randomized Comparison ofPercutaneous Coronary Intervention With Coronary Artery Bypass Grafting in Diabetic Patients CARDIA TRIALAkhil Kapur, Roger J. Hall, Iqbal S. Malik, Ayesha C. Qureshi, Jeremy Butts, et al www.cardiositeindia.com J Am Coll Cardiol. 2010;55(5):432-440.
    18. 18. CARDIA Trial HypothesisIn diabetic patients with multivessel disease amenable to both CABG or PCIOptimal PCI is no inferior to up to date CABG www.cardiositeindia.com J Am Coll Cardiol. 2010;55(5):432-440.
    19. 19. STUDY DESIGN Diabetic patients with multi vessel disease or complex single vessel disease Surgeon and interventionalist Amendable for both treatments Amendable for each treatment options approach Randomized arm N=600(1:1) Two registry armsDES vs CABGFollow up: 30d,6m, 1-5 yrsGoal: to define the most appropriatetreatment for diabetic patientsthrough randomized trial methods www.cardiositeindia.com
    20. 20. J Am Coll Cardiol. 2010;55(5):432-440.
    21. 21. CARDia Trial design Randomization Up to dateDiabetic patientswith multivessel Inclusion CABG Suitable for PCI and disease or exclusion CONSENT complex single or CABG criteria met vessel disease Optimal PCI stent + abciximab DES 71% BMS 29% www.cardiositeindia.com J Am Coll Cardiol. 2010;55(5):432-440.
    22. 22. Trial design• CABG historically assumed to be superior to PCI(based on BARI subset)• Investigator initiated trial designed to show non inferiority of PCI• Sample size of 600 patients based on ARTS and EPI trialsAnd the hypothesis(test of non inferiority) to be tested is: Ho: pe >= 1.3ps Ha: pe < 1.3ps• 510 patients recruited from Jan 2002 to May 2007 Early termination due to slowing recruitment but follow up extended to 5 years www.cardiositeindia.com J Am Coll Cardiol. 2010;55(5):432-440.
    23. 23. CARDia patient flow chart 510 patients randomized CABG PCI 254 patients 256 patients 8= withdrew consent 2=withdrew consent 1=data not available yet 2=data not available yet 229 received CABG 252 received PCI 1=died 1=cross over to 11=cross over to PCI CABG 96% (245) in 1 98% (251) in 1 year follow up year follow up www.cardiositeindia.com J Am Coll Cardiol. 2010;55(5):432-440.
    24. 24. Baseline clinical characteristics www.cardiositeindia.com J Am Coll Cardiol. 2010;55(5):432-440.
    25. 25. Results-adjudicated events- intention to treat analysis www.cardiositeindia.com J Am Coll Cardiol. 2010;55(5):432-440.
    26. 26. End points Primary endpoint:• Composite event rate at 1 year of death/non fatal MI/non fatal stroke (time to first event) Major secondary :• Further revascularization at 1 year Secondary:• Severe bleeding complications at 30 days• New requirement for permanent dialysis• Neurological morbidity• Quality of life• Cost difference between treatments• Change in LV function www.cardiositeindia.com J Am Coll Cardiol. 2010;55(5):432-440.
    27. 27. Individual 1 year outcomes www.cardiositeindia.com J Am Coll Cardiol. 2010;55(5):432-440.
    28. 28. PCI procedural details Use prior to procedure of:Aspirin-100%Clopidogrel- 94%Abciximab-95% 3 vessel disease- 65% 3 vessels treated in these patients-88%o Average no. of stents per patient- 3.5o Average stent length- 71mm DES patients (cypher)-71% (180) BMS patients- 29% (72) www.cardiositeindia.com
    29. 29. CABG procedural details 3 vessel disease- 58% 3 vessels treated in these patients- 90%Average number of grafts-2.8LIMAs- 89%% with at least two arterial grafts- 17%% off pump- 31% www.cardiositeindia.com J Am Coll Cardiol. 2010;55(5):432-440.
    30. 30. Survival at 1 year CABG vs PCI www.cardiositeindia.com J Am Coll Cardiol. 2010;55(5):432-440.
    31. 31. Primary composite outcome at 1 year www.cardiositeindia.com J Am Coll Cardiol. 2010;55(5):432-440.
    32. 32. ENPOINTS: Death ,MI, stroke and repeat revascularization www.cardiositeindia.com J Am Coll Cardiol. 2010;55(5):432-440.
    33. 33. CARDia: Main conclusions No apparent difference between PCI and CABG at 1 year in :• Death• Composite of death, MI and stroke More repeat revascularization In the PCI group PCI may now be considered a reasonable strategy in diabetic patients with multivessel disease Longer follow up is needed www.cardiositeindia.com J Am Coll Cardiol. 2010;55(5):432-440.
    34. 34. Future REvascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel diseaseFreedom trial www.cardiositeindia.com
    35. 35. Strategies for Multivessel Revascularizationin Patients with Diabetes FREEDOM TRIALMichael E. Farkouh, Michael Domanski, Lynn A. Sleeper,Flora S. Siami, George Dangas, Michael Mack, et al www.cardiositeindia.com
    36. 36. N Engl J Med 2012.
    37. 37. FREEDOM Design (1) Eligibility: DM patients with MV-CAD eligible for stent or surgery Exclude: Patients with acute STEMI Randomized 1:1 MV-Stenting CABG With Drug-eluting With or Without CPBAll concomitant Meds shown to be beneficial wereencouraged, including: clopidogrel, ACE inhibitors, ARBs, b-blockers, statins www.cardiositeindia.com
    38. 38. Freedom recruitment www.cardiositeindia.com N Engl J Med 2012.
    39. 39. Baseline Demographics Treatment Arm A B (N=593) (N=592) Age (mean) 63.4 63.0 Female 28.9% 29.5%Diabetes Mellitus: Type I 4.8% 4.8% Hypertension 83.9% 84.7% Hyperlipidemia 85.1% 81.9% www.cardiositeindia.com
    40. 40. Diabetes Complications Treatment Arm A B (N=593) (N=592) Complications in diabetes 18.0% 18.9%Diabetic nephropathy 4.9% 8.6%Diabetic neuropathy 11.2% 8.8%Diabetic foot ulcer 2.8% 0.7%Diabetic retinopathy 6.3% 7.6%Extremity amputation 1.2% 0.2%Duration of diabetes (years) 10.1 10.3 PVD above diaphragm 1.9% 3.4% PVD below diaphragm 10.0% 8.3% www.cardiositeindia.com N Engl J Med 2012.
    41. 41. History of Present Illness A B (N=593) (N=592)Stable Coronary Heart Disease 68.3% 71.4%Acute Coronary Syndrome (ACS) 31.7% 28.6%ST elevation MI(>72 hrs prior to 17.1% 17.3%admission 82.9% 82.7%Non-ST elevation ACSNYHA CHF Classification (Class III/IVexcluded)Class I 74.5% 72.6% www.cardiositeindia.com N Engl J Med 2012.
    42. 42. Interventional – Pre-Stent Process• Prior to PCI: Clinical suitability of each lesion – left main was an absolute exclusion - Certified operator PCI within 14 days of randomization• DES: For all lesions Only one type for any given FREEDOM patient• Antithr: Oral ASA 325 mg + Clopid. > 300 mg load , Unfractionated Heparin or Bivalirudin, Abciximab on the initial PCI ASA 81-100 mg + Clopid. 75 mg/day 1-yr www.cardiositeindia.com N Engl J Med 2012
    43. 43. PCI Procedure Summary PCI/DESStaging: % unstaged procedure 65.9%% staged procedure 34.1%% staged procedures involving >1 67.7%hospitalizationMean total # of lesions attempted 3.6 ± 1.4Mean total # drug-eluting stents placed per patient(across all stages) 4.2 ± 1.9Reopro used during index procedure (stage 1 forstaged procedures) 54.9%Heparin administered 83.1%Bivalirudin administered 16.3% www.cardiositeindia.com N Engl J Med 2012.
    44. 44. CABG Management• The use of an internal mammary artery (IMA) to the left anterior descending (LAD) was strongly recommended in all patients• The surgical approach - conventional CABG with cardiopulmonary bypass and cardioplegic arrest or off- pump CABG with beating heart - was left to the individual surgeon’s judgement www.cardiositeindia.com
    45. 45. CABG Procedure Summary CABGOff – pump 22.1%LIMA to LAD 88.2% www.cardiositeindia.com N Engl J Med 2012.
    46. 46. ENDPOINTS EventsEndpoint PCI CABG Relative Risk 95% CiCV Events 205 / 953 147 / 947 1,39 [1,14;1,68] (21,5%) (15,5%)Death From Any 118 / 953 86 / 947 1,36 [1,05;1,77]Cause (12,4%) (9,1%)MI 99 / 953 48 / 947 2,05 [1,47;2,86] (10,4%) (5,1%)Stroke 22 / 953 37 / 947 0,59 [0,35;0,99] (2,3%) (3,9%)Cardiovascular 75 / 953 55 / 947 1,36 [0,97;1,90]Death (7,9%) (5,8%) www.cardiositeindia.com N Engl J Med 2012.
    47. 47. PRIMARY OUTCOME :DEATH / STROKE / MI PCI/DES 30 CABG Death/Stroke/MI, % Logrank P=0.005 PCI/DES 20 CABG 10 5-Year Event Rates: 26.6% vs. 18.7% 0 0 1 2 3 4 5 6 Years post-randomization PCI/DES N=953 848 788 625 416 219 40 CABG N=943 814 758 613 422 221 44 www.cardiositeindia.com
    48. 48. MYOCARDIAL INFARCTION PCI/DES Myocardial Infarction, % 30 CABG Logrank P<0.0001 20 13.9 % PCI/DES 10 6.0% CABG 0 0 1 2 3 4 5 Years post-randomizationPCI/DES N 953 853 798 636 422 220 CABG N 947 824 772 629 432 229 www.cardiositeindia.com
    49. 49. All-cause mortality 30 PCI/DES CABG All-Cause Mortality, % 20 Logrank P=0.049 PCI/DES 10 CABG 0 5-Year Event Rates: 16.3% vs. 10.9% 0 1 2 3 4 5 Years post-randomizationPCI/DES N 953 897 845 685 466 243 CABG N 947 855 806 655 449 238 www.cardiositeindia.com
    50. 50. Repeat revascularization 30 PCI/DES Repeat Revascularization, % CABG Log rank P<0.0001 20 13% 10 PCI/DES 5% CABG 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months post-procedurePCI/DES N 944 887 856 818 792 CABG N 911 858 836 825 806 www.cardiositeindia.com
    51. 51. MACE (Death / Stroke / MI / Repeat-Revascularization) 30 PCI/DES CABG Logrank P=0.004 MACCE, % 20 17% PCI/DES 10 12% CABG 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months post-procedure PCI/DES N 944 873 842 803 773 CABG N 911 825 805 794 773 www.cardiositeindia.com
    52. 52. Primary endpoint – death / stroke / mi treatment / syntax interaction - p=0.58 SYNTAX Score  22 SYNTAX Score 23-32 Freedom from Event (%) Freedom from Event (%) 100 100 90 (N=669) 90 (N=844) 80 80 70 5-Year Event Rates: 23.2% 70 5-Year Event Rates: 60 60 50 17.2% 50 27.2% 17.7% 40 40 30 PCI/DES 30 PCI/DES 20 20 10 CABG 10 CABG 0 0 0.0 1.0 2.0 3.0 4.0 5.0 0.0 1.0 2.0 3.0 4.0 5.0 Years post-randomization Years post-randomization SYNTAX Score  33 Freedom from Event (%) 100 90 (N=374) 80 5-Year Event Rates: 70 60 30.6% 50 40 PCI/DES 30 22.8% 20 10 CABG 0 0.0 1.0 2.0 3.0 4.0 5.0 Years post-randomization www.cardiositeindia.com
    53. 53. FREEDOM Trial conclusionFor patients with diabetes and advanced Coronary artery diseaseCABG was superior to PCICABG significantly reduced rates of death and myocardial infarction,But had a higher rate of stroke. www.cardiositeindia.com N Engl J Med 2012.
    54. 54. Limitations of the Trial On a long term disease, this is a relatively short term study – 7 years, with a minimum of 2 years and a median of 3.8 years. Longer term follow up of FREEDOM will lead to betterunderstanding of the comparative benefit by CABG, specifically onmortality www.cardiositeindia.com
    55. 55. Critical Analysis of FREEDOM Trial• 1010 patients: smaller sample• Average age of participants is 62; whereas most diabetic patients fall in 70- 80 and higher age group• The average syntax score was 46, and 1/3rd population fell into greater than 33 syntax score which anyway qualifies them for CABG Hence is DM a further risk?• Inspite of flaws this trial gives a general guideline in management of diabetes with multivessel disease www.cardiositeindia.com
    56. 56. THANK YOU!! www.cardiositeindia.com

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