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Upendra Kaul, MD for the TUXEDO INDIA Investigators

Paclitaxel Eluting Versus Everolimus Eluting Stents in Patients with Diabetes Mellitus and Coronary Artery Disease One Year Clinical Results. Upendra Kaul, MD for the TUXEDO INDIA Investigators. Tuxedo India. Disclosures. Upendra Kaul, MD

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Upendra Kaul, MD for the TUXEDO INDIA Investigators

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  1. Paclitaxel Eluting Versus Everolimus Eluting Stents in Patients with Diabetes Mellitus and Coronary Artery Disease One Year Clinical Results Upendra Kaul, MDfor the TUXEDO INDIA Investigators

  2. Tuxedo India Disclosures • Upendra Kaul, MD • Boston Scientific: Research Grant and Lecture Fee • Abbott Vascular: Lecture Fee

  3. Tuxedo India PCI in Patients With Diabetes Why are They at Increased Risk ? • More extensive disease, more complex lesions • Clustering of risk factors and co-morbidities • Profound proliferative vascular response High risk for restenosis • Prothrombotic state: Increased platelet activation, increased levels of tissue factor, fibrinogen and PAI-I • Endothelial dysfunction High risk for stent thrombosis DES have replaced BMS in diabetics because of reduced ISR and need for TVR

  4. Tuxedo India TUXEDO- India Background • Choice of a DES in diabetic population has been debatable • Results between Limusanalogues and Paclitaxel have been contradictory • A meta analysis of Spirit II, III, IV and Compare studies showed equivalent results between PES and EES in diabetics (Stone GW et al. Circulation 2011;124:893-900) • On the contrary, in a mixed treatment analysis of 48 randomized trials EES was shown to be the best in diabetics (Bangalore S, et al. BMJ 2012;345:e5170) • In the absence of a dedicated adequately powered randomized study a definitive answer is not possible

  5. Tuxedo India Tuxedo India Study Algorithm RVD ≥2.25 mm - ≤4 mm; Lesion length ≤34 mm Upto 3 lesions with a maximum of 2 per epicardial vessel 1830 patients enrolled at 46 Indian sites Pre-rand: ASA ≥300 mg, clopidogrel ≥300 mg load unless on chronic Rx or Prasugrel 60 mg or Ticagrelor 180 mg Randomized 1:1 TAXUS ElementTM : XIENCE PrimeTM Pre-dilatation mandatory Paclitaxel-eluting TAXUS Everolimus-eluting XIENCE Aspirin ≥75 mg QD for long term; clopidogrel 75mg QD for at least 12 months or Ticagralor 90 mg BD or Prasugrel 10 mg OD (if not at high risk for bleeding) Clinical f/u only: 1, 6 months, 1 year and 2 years

  6. Tuxedo India End Points Patients with Stable CHD or ACS undergoing PCI 1:1 Randomization Paclitaxel-eluting stent (TAXUS ) Everolimus-eluting stent (XIENCE) Primary Endpoint: TVF: Composite of Cardiac Death, Target vessel MI or Ischemia-Driven TVR at 1-Year Secondary Endpoints: Death, Cardiac Death, MI, TLR, TVR, MACE, Definite and Probable ST

  7. Tuxedo India Sample Size Calculation • Statistical Method • A two-group Farrington-Manning test was used to test the one-sided hypothesis of non inferiority in proportions. • Sample Size Parameters • Expected TAXUS Element™TVF rate = 8.4% • Expected XIENCE Prime™TVF rate = 8.4% (based on data from the SPIRIT trials) • Non-inferiority margin (Δ) = 4.0% (absolute) • Test significance level () = 0.05 (1-sided) • Power (1) = approximately 0.90 • Expected rate of attrition = 10% • N=1,830 patients

  8. Tuxedo India Key Eligibility Criteria For Enrolment

  9. Tuxedo India Tuxedo India Patient Flow Enrolled (N=1851) 21 = Screen Failed Randomized (N=1830) XIENCE(N=916) TAXUS (N=914) 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%) XIENCE(N=896) TAXUS (N=887)

  10. Tuxedo India Baseline Demographics (ITT Analysis)

  11. Tuxedo India Baseline Clinical Data (ITT Analysis)

  12. Tuxedo India Lesion Details (ITT Analysis)

  13. Tuxedo India Procedural Characteristics (ITT Analysis) * Statistically significant

  14. Tuxedo India Antiplatelet Agent Used XIENCE TAXUS P=0.04 NA P=0.04 (%) 916/916 914/914 647/914 688/916 647/914 688/916 Aspirin + Ticagrelor/Prasugrel or Clopidogrel Aspirin + Clopidogrel Aspirin + Ticagrelor/Prasugrel

  15. Tuxedo India Non-inferiority Assessment for the Primary Efficacy Endpoint Target Vessel Failure TAXUS 5.6% vs. XIENCE 2.9% P non-inferiority = 0.38 Difference: 2.7% Upper one-sided 95% CI: 4.48% 3.0% −1.0% 0% 1.0% 4.0% 2.0% 5.0% Non-inferiority margin

  16. Tuxedo India Target Vessel Failure Rate at 1 Year HR [95%CI] = 1.64 [1.09-2.47] P=0.02 by log-rank test PNI=0.38 by F-M test PSUP= 0.005 PES EES *5.9% Cumulative Incidence (%) *3.2% Months *Events calculated with Kaplan-Meier methods and compared with the use of the log-rank test. Differs slightly from graph which were calculated as categorical variables and compared with use of Chi-Square test.

  17. Tuxedo India Components of TVF XIENCE TAXUS P=0.002 P<0.001 P=1.00 (%) 26/914 5/916 16/914 16/916 11/916 31/914

  18. Ischemia Driven TLR Rate at 1 Year HR [95%CI] = 2.18 [1.20-3.95] P=0.009 by log-rank test TAXUS XIENCE Cumulative Incidence (%) Months *Events calculated with Kaplan-Meier methods and compared with the use of the log-rank test. Differs slightly from graph which were calculated as categorical variables and compared with use of Chi-Square test.

  19. Tuxedo India Death and MI at 1 Year

  20. Tuxedo India Cardiac Death or TV-MI Rate at 1 Year HR [95%CI] = 1.69 [1.04-2.75] P=0.03 by log-rank test TAXUS XIENCE Cumulative Incidence (%) Months *Events calculated with Kaplan-Meier methods and compared with the use of the log-rank test. Differs slightly from graph which were calculated as categorical variables and compared with use of Chi-Square test.

  21. Tuxedo India Stent Thrombosis Rate at 1 Year HR [95%CI] = 5.08 [1.74-14.87] P<0.001 by log-rank test TAXUS XIENCE Cumulative Incidence (%) Months *Events calculated with Kaplan-Meier methods and compared with the use of the log-rank test. Differs slightly from graph which were calculated as categorical variables and compared with use of Chi-Square test.

  22. Tuxedo India Stent Thrombosis Acute (<24 hours) Subacute (24 hours – 30 days) Late (>30 days – 1 year) 2.1% TAXUS n=914 P=0.002 0.4% XIENCEn=916 Stent thrombosis (%)

  23. Tuxedo India Tuxedo India: 12 Subgroups Examined Age < 65 (n=1372) No. of Treated Lesions = 1 (n=1344) Age ≥ 65 (n=458) No. of Lesion Treated Lesion ≥ 2 (n=457) Male (n=1377) Female (n=453) Insulin Therapy Requirement (n=747) Lesion Type A (n=84) No requirement (n=1083) Lesion Type B (n=969) Lesion Type C (n=987) Hb1Ac < 7% (n=419) Lesion Length ≤ 20 mm (n=1186) Hb1Ac ≥ 7% (n=1259) Lesion Length > 20 mm (n=824) eGFR ≤ 60 ml/min (n=347) Target Vessel LAD (n=1056) eGFR > 60 ml/min (n=1474) Non-LAD (n=1027) ACS (n=1186) Stable angina (n=644) RVD ≤ 2.75 mm (n=949) Duration of Diabetes < 5 Years (n=893) Duration of Diabetes ≥ 5 Years (n=837) RVD > 2.75 mm (n=1048)

  24. Tuxedo India Tuxedo India Sub group Analysis: TVF at 1 Year PES better EES better TVF = cardiac death, target vessel MI, or ischemia-driven TVR

  25. Tuxedo India Tuxedo India Sub group Analysis: TVF at 1 Year PES better EES better

  26. Tuxedo India Tuxedo India Conclusions In this largest trial of patients with diabetes, paclitaxel-eluting stent compared to everolimus-eluting stent at 1-year follow-up demonstrated: • Primary endpoint: PES failed to meet non-inferiority as compared to EES. Had higher rates of TVF. On superiority testing EES proved superior. • Major secondary endpoints: Significantly higher rates of MI, stent thrombosis, TVR, TLR, composite of cardiac death or TV-MI and MACE for PES arm. • Subgroup Analysis: Insulin requiring diabetics behaved like non insulin requiring with EES superior to PES. • The only subgroup where PES and EES had similar results were patients with an e GFR of <60 ml/min.

  27. Tuxedo India Clinical Implications • The study supports the current worldwide practice of use of new generation limus stents even in patients with insulin requiring diabetes mellitus. This may have important implications for PES. • The results question the outcomes of FREEDOM and BARI-2D showing superiority of CABG since Ist generation stents which are inferior to EES were used as comparators.

  28. Tuxedo India TUXEDO – Study OrganizationInvestigator Initiated Study Principal Investigator : Upendra Kaul Operations Committee : Priyadarshini Arambam (Head) Steering Committee : Ashok Seth (Chair) CEC : Sanjay Tyagi MD (Chair) DSMB : Rajendra Tandon MD (Chair) Randomization Service : Max Neeman International Data Management : Max NeemanInternational Funded by : Boston Scientific Corp

  29. Tuxedo India TUXEDO – Participating Centres (N=46)

  30. Tuxedo India TUXEDO –Top 15 Enrollers

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