ΑΓΓΕΙΟΠΛΑΣΤΙΚΗ ΣΤΟ ΔΙΑΒΗΤΙΚΟ ΑΣΘΕΝΗ

Transcription

1 ΑΓΓΕΙΟΠΛΑΣΤΙΚΗ ΣΤΟ ΔΙΑΒΗΤΙΚΟ ΑΣΘΕΝΗ Νίκος Μεζίλης MD, FESC Κλινική Άγιος Λουκάς

2 Why diabetes is associated with restenosis endothelial dysfunction metabolic alterations accelerated platelet deposition propensity to growth factors known to promote the restenosis. advanced glycosylation promotes inflammatory cell recruitment smooth muscle cell proliferation

3 5-Year Outcomes of the SYNTAX Trial Mohr FW et al. Lancet 2013; 381: MACCE: Death, MI, Stroke, or Repeat Revasc

4 MACCE to 5 Years by SYNTAX Score Mohr FW et al. Lancet 2013; 381: Low Scores (0-22) PCI CABG Death P=0.64 MI P=0.11 Intermediate Scores (23-32) Death P=0.68 MI P= High Score 33 Death P=0.005 MI P=0.004

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7 Revascularisation strategies in diabetic patients with CAD Trial MVD EF (%) (%) N Primary Endpoint FU (y) Trial Results 57 Death 5 No differences in death and MACE Death Death Death, MI or stroke Death, MI or stroke Death or MI 2 Revascularisation vs. medical therapy BARI-2Dw60 (2009) CABG stratum BARI-2Dw60 (2009) Lower rates of MI with CABG PCI stratum BARI-2Dw60 (2009) No differences in death and MACE PCI vs. CABG CARDiaw61 (2010) FREEDOM (2012)55 VA-CARDSw62 (2013) SYNTAX (2013) Favours CABG - Death, MI, stroke or repeat revascularisation 1 Failure to demonstrate noninferiority of PCI Lower rates of death, MI or stroke with CABG No differences in death or MI Lower rates of death, MI, stroke or repeat revascularisation with CABG

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9 FREEDOM Design (1) Eligibility: DM patients with MV-CAD eligible for stent or surgery Exclude: Patients with acute STEMI, Prior CABG, PCI/ Stent within 6 months Randomized 1:1 MV-Stenting With Drug-eluting CABG With or Without CPB All concomitant Meds shown to be beneficial were encouraged, including: clopidogrel, ACE inhib., ARBs, b-blockers, statins Farkouh ME et al N Engl J Med; 367:

10 FREEDOM Baseline Features Total subjects Two vessel disease Three vessel disease LAD involved SYNTAX score # stents/patient SES/PES %/43%

11 PRIMARY OUTCOME DEATH / STROKE / MI CABG PCI/DES Logrank P= PCI/DES 20 CABG Death/Stroke/MI, % 10 5-Year Event Rates: 26.6% vs. 18.7% Years post-randomization PCI/DES N CABG N

12 PRIMARY ENDPOINT DEATH / STROKE / MI TREATMENT / SYNTAX INTERACTION - p= SYNTAX Score 22 (N=669) Year Event Rates: 23.2% 17.2% Freedom CABG Year Event Rates: Freedom 10 0 PCI/DES from Event (%) SYNTAX Score (N=844) 5.0 PCI/DES from Event (%) CABG Years post-randomization Years post-randomization SYNTAX Score 33 (N=374) Freedom Year Event Rates: % 17.7% 30.6% 22.8% PCI/DES from Event (%) CABG Years post-randomization

13 MYOCARDIAL INFARCTION PCI/DES CABG 30 Logrank P< % Myocardial Infarction, % PCI/DES 6.0% 10 CABG Years post-randomization PCI/DES N CABG N

14 STROKE Severely Disabling Scale CABG PCI/DES NIH > 4 55% Rankin >1 70% 27% 60% CABG PCI/DES Stroke, % Logrank P= % CABG 2.4% PCI/DES Years post-randomization PCI/DES N CABG N

15 Quality of Life After PCI vs CABG Among Patients With Diabetes and Multi-vessel Coronary Artery Disease: A Randomized Clinical Trial: FREEDOM Figure Legend: Frequency of Angina by Treatment Group Frequency of angina by treatment group according to the Seattle Angina Questionnaire (SAQ) angina frequency scale. Categories (with scores by increments of 10) were defined as no angina (score, 100), monthly angina (score,70-90), weekly angina (score, 40-60), or daily angina (score, <40). JAMA. 2013;310(15): doi: /jama

16 Meta-analysis: DES vs CABG in Diabetic Patients Hakeem A et al. J Am Heart Assoc EP MACE: Death, MI, or 4 Years Sensitivity Analysis According to SYNTAX score

17 Verma S., et al. Lancet Diabetes Endocrinol 2013

18 2014ACC/AHAStable Ischemic Heart Disease Focused Update

19 CABG in Patients with Diabetes in NY FREEDOM

20 Issues with FREEDOM 1. Selection Bias 2. Diabetes is not important for decision making for PCI versus CABG 3. PCI arm would have done better if later generation DES and newer stents were available 4. An ischemia guided approach would have shown a different outcome 5. Higher rates of Stroke in the CABG arm

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22 CABG vs. PCI

23 Do Contemporary DES Change the Equation for PCI vs CABG in the Diabetic Patient?

24 Gap between PCI and CABG Non-stent Related Events Stent Related Events Restenosis Stent Thrombosis Neoatherosclerosis Death and MI

25 Drug Eluting Stents CYPHER Strut Thickness: 140 mm Polymer Thickness: 13.7 mm TAXUS Liberté Strut Thickness: ENDEAVOR XIENCE V Strut Thickness: Strut Thickness 97 mm 91 mm 81 mm Polymer Thickness Polymer Thickness Polymer Thickness 17.8 mm 4.8 mm 7.8 mm

26 DES Polymer Changes 1st Gen 2nd Gen Non uniform polymer coating Uniform polymer coating Webbing and bonding No webbing and bonding Delamination No delamination

27 14 Day Endothelialization: Rabbit Iliac Model XIENCE V CYPHER TAXUS Joner and Virmani, JACC 2008 ENDEAVOR

28 Inflammation Rabbit double-injury iliac artery model at 28 days follow-up P = P = Inflammatory Cells/strut (N) XIENCE N= ResoluteTM N=16 Van Dyck CJ. et al, Catheter Cardiovasc Interv Aug 6. BMS* N=16

29 In vitro pulsatile Chandler loop model with porcine blood 2 49% ; P< µm) % ; P= LDH Adsorbance Stentadhesion formulation / 0.6 forcell Relative platelet LDH Adsorbance for MULTI-LINK VISION ( TS = thick strut 0.0 Conclusions: MULTI-LINK VISION (81 µm) TS VISION (162 µm) XIENCE V (96.6 µm) Contrary to popular perception, drug/polymer coatings do not inherently increase acute stent clotting; they reduce thrombosis Kolandaivelu et al. Circulation. 2011;123:

30 Kaul U, Bangalore et al. N Engl J Med. 2015

31 Tuxedo India Patient Flow Enrolled (N=1851) 21 = Screen Failed Randomized (N=1830) TAXUS (N=914) XIENCE (N=916) Withdrawal = 12 Lost to f/u = 10 Investigator decision = 5 9 = Withdrawal 9 = Lost to f/u 2 = Investigator decision 1-Year Follow-up (N=1783; 97.4%) TAXUS (N=887) Kaul U, Bangalore et al. N Engl J Med XIENCE (N=896) Tuxedo India

32 Tuxedo India Primary End Point: Target Vessel Failure Rate at 1 Year HR [95%CI] = 1.64 [ ] P=0.02 by log-rank test PNI=0.38 by F-M test PSUP= TAXUS *5.9% *3.2% Cumulative Incidence (%) XIENCE Months Number at risk PES EES Kaul U, Bangalore et al. N Engl J Med. 2015

33 Tuxedo India Cardiac Death or TV-MI Rate at 1 Year HR [95%CI] = 1.69 [ ] P=0.03 by log-rank test TAXUS Cumulative Incidence (%) XIENCE Months Number at risk PES EES Kaul U, Bangalore et al. N Engl J Med. 2015

34 Stent Thrombosis Rate at 1 Year Tuxedo India HR [95%CI] = 5.08 [ ] P<0.001 by log-rank test TAXUS Cumulative Incidence (%) XIENCE Months Number at risk PES EES Kaul U, Bangalore et al. N Engl J Med. 2015

35 consecutive stent implantations Conclusions: PCI with n-des is associated with a 38% lower risk of restenosis, 43% lower definite ST, and a 23% lower risk of death compared with o-des Sarno et al. European Heart Journal (2012) 33,

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43 Bangalore et al. BMJ 2012; 345:e1510

44 EES vs CABG for Patients With Diabetes and Multivessel Disease Analysis of 8,096 propensity-matched patients from New York State registries, Mortality rates favored the EES group at 30 days (0.57% vs 1.11%; P =.04), though long-term data showed similar mortality between the EES and CABG arms (10.50% vs 10.23%; P =.16) MI risk was higher with EES vs CABG, but not in the subset of patients who had complete revascularization (P =.30) EES were linked with less stroke but more revascularization Conclusion: With similar long-term survival, second-generation DES and CABG may be reasonable options for diabetics with multivessel disease. Bangalore S, et al. Circ Cardiovasc Interv. 2015;Epub ahead of print.

45 Conclusions Data from multiple sources suggest consistent superiority of newer generation DES over 1st generation DES for efficacy and safety It is not clear if CABG would have a mortality benefit when compared with newer generation DES The decision about CABG vs. PCI should be based on: Ability to completely revascularize Weighing short term risk of death and stroke with CABG with long term benefit of reducing the risk of repeat revasc Patient preference

46 Diminishing Mortality Gap between PCI and CABG: NY State Registry (JACC 1999) POBA (NEJM 2005) (NEJM 2008) BMS 1st Gen DES (NEJM 2015) 2nd Gen DES NS 20-29% 24-36% 40-50% Favors PCI Favors CABG

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51 Specific recommendations for diabetic patients. The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Eur J Cardiothorac Surg 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. 2010;38:S1-S52

52 Recommendations for prevention of contrast-induced nephropathy. The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Eur J Cardiothorac Surg 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. 2010;38:S1-S52

53 Specific Recommendations For Revascularization in Patients With Diabetes. Windecker S et al. Eur Heart J 2014;35:

54 Choosing wisely between PCI and CABG Patient Preference Matters!!!!!! Risk of shortterm death and stroke Risk of long-term repeat revascularization* CABG * Risk of MI in patients with incomplete revascularization PCI

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56 Definite Stent Thrombosis: Probability Best % Probability of Lowest ST Rate PtCr-EES, 18 ZES-R,0 ZES,0 PES,0 BP-DES,0 BMS,0 PES/SES 0% Probability CoCr-EES, randomized trials and patient-years of follow-up Bangalore et al. BMJ 2013; 347:f6625

57 All-Cause Mortality: Probability Best % Probability of Lowest Death Rate PES,0 SES,0 BP-DES,6CoCrEES,18 BMS,0 ZES-R,40 0% Probability PES/SES PtCr EES, 31 ZES-E,2 126 RCTs and >258,000 patient-years of follow-up Bangalore et al. BMJ 2013; 347:f6625

58 Myocardial infarction: Probability Best % Probability of Lowest MI Rate BMS,0 PES,0 ZES-R,26.36 SES,0.08 EES,46.9 ZES, RCTs with >117, 000 PY of follow up Bangalore et al. Circulation. 2012;125:

59 Definite Stent Thrombosis 126 RCTs and >258,000 patient-years of follow-up BMS DES RR (95% CrI) SES vs. BMS 1.01 ( ) PES vs. BMS 1.17 ( ) CoCr EES vs. BMS 0.35 ( ) PtCr EES vs. BMS 0.50 ( ) ZES-E vs. BMS 0.79 ( ) ZES-R vs. BMS 0.88 ( ) 0.71 ( ) BP-DES vs. BMS 0 1 Risk Ratio (95% Crl) Bangalore et al. BMJ 2013; 347:f

60 Bangalore et al. Circ Cardiovasc Interv Aug;7(4):518-25

61 Outcome: Mortality CABG vs. PCI in Diabetics Bangalore et al. Circ Cardiovasc Interv Aug;7(4):518-25

62 In patients with DM and MV CAD, CABG was superior to PCI by reducing rates of death and myocardial infarction with a higher rate of stroke Primary Outcome: Death, Stroke, MI The Trial was Heavily Criticized because not all 3VDs are similar 3VD + DM 3VD + DM 3VD + DM

63 Role of Diabetes The FREEDOM Trial 1900 diabetics with MVD randomized to DES vs CABG; mean SYNTAX score = 26 NEJM 2012;367:

64 Strategies for Multivessel Revascularization in Patients with Diabetes the FREEDOM Trial Farkouh ME et al. N Engl J Med 2012; 367: Death, MI, or Stroke Through 5 Years Median SYNTAX-Score = % 13.0% 11.9% 18.7%

65 Meta-analysis: DES vs CABG in Diabetic Patients Hakeem A et al. J Am Heart Assoc EP MACE: Death, MI, or 4 Years Sensitivity Analysis According to SYNTAX score

66 What s next?

67 FAME III PCI vs CABG using FFR in the PCI patients and stenting only the positive lesions 1500 patients randomized About 500 diabetic patients may be too few to have adequate power

68 Mixed treatment comparison analyses for all-cause mortality Bangalore S et al. Circ Cardiovasc Interv. Copyright 2014;7: American Heart Association, Inc. All rights reserved.

69 What is the current equation for CABG vs. PCI? CABG reduces need for repeat revascularization CABG reduces myocardial infarction (longterm) Protection from future plaque rupture in the bypassed segments CABG reduces risk of death (long-term)