Cobalt-Chromium Paclitaxel-eluting Stent vs. identical BMS

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  • Configuration of Conor polymer/drug inlays dictate both direction and release kinetics Different drug concentration gradients yield different release kinetics Barrier layers are slowly degrading polymers which control directionality
  • Cobalt-Chromium Paclitaxel-eluting Stent vs. identical BMS

    1. 1. EuroSTAR II The European Randomized CoStar ™ Trial: Cobalt-Chromium Paclitaxel-eluting Stent vs. identical BMS Sigmund Silber, MD, FACC, FESC Cardiology Practice and Hospital Munich, Germany [email_address]
    2. 2. Disclosure <ul><li>Consulting fees and honoraria from various companies, </li></ul><ul><li>No stocks or patents, no conflict of interest related to this presentation </li></ul>EuroSTAR II
    3. 3. CoStar™ Stent Platform UniStar™ Cobalt Chromium stent platform PLGA Bioresorbable polymer Paclitaxel EuroSTAR II
    4. 4. CoStar ™ Resorbable Polymer- Animal Data No residual polymer following tissue removal at 180 days Explant In-vivo porcine model EuroSTAR II
    5. 5. CoStar™ Stent Design Bridge Elements Reservoirs Ductile Hinges Alternating hexagonal pattern EuroSTAR II
    6. 6. CoStar™ Stent Design Bridge Elements Reservoirs Ductile Hinges Alternating hexagonal pattern EuroSTAR II highly deliverable
    7. 7. CoStar™ Stent Design Bridge Elements Reservoirs Avoid possible cracking of polymer EuroSTAR II Ductile Hinges
    8. 8. The Power of Reservoir Technology Single Drug Structure Multiple Drug Structures Drug Delivery Reservoirs Bi-Directional Uni-Directional Single Adjacent EuroSTAR II
    9. 9. <ul><li>Objective: </li></ul><ul><li>To compare the the CoStar ™ Paclitaxel-Eluting Coronary Stent System to the same stent without a drug or polymer. </li></ul><ul><li>Dose: 10 µg / 30 days (in-vitro) </li></ul>EuroSTAR II Trial Prospective, Multi-Center, Randomized, Study of the CoStar ™ Paclitaxel-eluting Coronary Stent System in Patients with De Novo Lesions of Native Coronary Arteries EuroSTAR II
    10. 10. Study Administration EuroSTAR II Principal Investigator: Prof. Dr. S. Silber, Munich , Germany Data Coordinating Center: DATATRAK Deutschland GmbH Bonn, Germany Steering Committee: Prof. Dr. S. Silber, Munich , Germany Dr. Suryapranata, Zwolle, Netherlands Dr. B. Chevalier, Saint-Denis, France QCA Core Lab: Bio-Imaging Technologies Leiden, The Netherlands Data Safety Monitoring Committee / Clinical Events Committee Dr. Marcus Lins, Kiel, Germany Prof. Dr. Blanchard, France Jan Bart Hak, Netherlands (Chairman) Sponsor: BIOTRONIK GmbH & Co. KG
    11. 11. Study Design Prospective, Randomized, Multi-Center European Study Lesions  25 mm in length, 2.5 – 3.5 mm diameter 303 Patients at 18 Centers UniStar ™ Coronary Stent (Control Group) N = 151 CoStar ™ Paclitaxel-eluting Stent N = 152 Randomized 1:1 Antiplatelet Therapy: Clopidogrel 300 mg loading dose, 75 mg QD for  6 months Aspirin 100 mg QD for 6 months, and daily ASA indefinitely EuroSTAR II
    12. 12. Study Endpoints <ul><li>Primary </li></ul><ul><li>In-segment binary angiographic restenosis at 8 months </li></ul><ul><li>Secondary </li></ul><ul><li>Angiographic Endpoints </li></ul><ul><ul><li>In-stent late lumen loss at 8 months </li></ul></ul><ul><ul><li>In-stent and in-lesion minimum lumen diameter (MLD) </li></ul></ul><ul><li>Clinical Endpoints </li></ul><ul><ul><li>MACE at 30 days and 8 months </li></ul></ul><ul><ul><li>Target lesion revascularization (TLR) and target vessel revascularization (TVR) at 8 months </li></ul></ul>EuroSTAR II
    13. 13. Statistical Assumptions <ul><li>Assumptions: </li></ul><ul><ul><li>5% in treatment group </li></ul></ul><ul><ul><li>15% in control group </li></ul></ul><ul><ul><li> = 0.05 and  = 0.2 </li></ul></ul><ul><li>110 patients needed to provide 80% power to detect a difference in the primary endpoint of in-segment binary restenosis </li></ul><ul><li>A total of 150 patients will be needed in each group due to an assumed 25% lost to follow-up </li></ul>EuroSTAR II
    14. 14. Key Inclusion Criteria <ul><li>Up to two discrete de-novo lesions in two native coronary arteries </li></ul><ul><li>Stenosis between 50-99% (visual estimate) </li></ul><ul><li>Reference vessel diameter (RVD) 2.5 – 3.5 mm </li></ul><ul><li>Lesion length  25 mm </li></ul><ul><li>TIMI flow 1 or higher </li></ul>EuroSTAR II
    15. 15. Study Investigators EuroSTAR II Site Name and Location Investigator Campus Benjamin Franklin, Berlin , D Herzzentrum NRW, Bad Oeynhausen, D Universit ätsklinik, Würzburg, D Antonius Zh Nieuwegein, NL Isala Klinicken Zwolle, NL OLVG Amsterdam, NL Cardiology Practice and Hospital, Munich, D Kliniken GmbH, Bad Segeberg, D Universit ätsklinik, Rostock, D Vu Medisch Centrum, Amsterdam, NL Universit ätsklinik, Regensburg, D Zentralklinik, Bad Berka, D Vivantes Klinikum Spandau, Berlin, D Vivantes Friedrichshain, Berlin, D AHK, Wien, A Vivantes Klinikum Neuk ölln, Berlin, D Vivantes GmbH Reinickendorf, Berlin, D Vivantes Klinikum Am Urban, Berlin, D Dr. M. Wiemer Dr. B. Witzenbichler Dr. M. J. Suttorp Dr. H. Suryapranata Prof. Dr. C. Nienaber Dr. K. M. J. Marques Prof. Dr. A. Jeron PD Dr. B. Lauer, Dr. M. Jereczek Dr. S. Hoffmann Prof. Dr. W. Voelker Dr. T. Slagboom Prof. Dr. S. Silber Prof. Dr. G. Richardt Prof. Dr. H. D. Glogar Prof. Dr. H. Darius Prof. Dr. S. Behrens Prof. Dr. D. Andresen
    16. 16. Study Investigators EuroSTAR II 18 Sites in 3 European States Site Name and Location Investigator Campus Benjamin Franklin, Berlin , D Herzzentrum NRW, Bad Oeynhausen, D Universit ätsklinik, Würzburg, D Antonius Zh Nieuwegein, NL Isala Klinicken Zwolle, NL OLVG Amsterdam, NL Cardiology Practice and Hospital, Munich, D Kliniken GmbH, Bad Segeberg, D Universit ätsklinik, Rostock, D Vu Medisch Centrum, Amsterdam, NL Universit ätsklinik, Regensburg, D Zentralklinik, Bad Berka, D Vivantes Klinikum Spandau, Berlin, D Vivantes Friedrichshain, Berlin, D AHK, Wien, A Vivantes Klinikum Neuk ölln, Berlin, D Vivantes GmbH Reinickendorf, Berlin, D Vivantes Klinikum Am Urban, Berlin, D Dr. M. Wiemer Dr. B. Witzenbichler Dr. M. J. Suttorp Dr. H. Suryapranata Prof. Dr. C. Nienaber Dr. K. M. J. Marques Prof. Dr. A. Jeron PD Dr. B. Lauer, Dr. M. Jereczek Dr. S. Hoffmann Prof. Dr. W. Voelker Dr. T. Slagboom Prof. Dr. S. Silber Prof. Dr. G. Richardt Prof. Dr. H. D. Glogar Prof. Dr. H. Darius Prof. Dr. S. Behrens Prof. Dr. D. Andresen
    17. 17. Demographics and Clinical Characteristics EuroSTAR II CoStar n = 152 UniStar n = 151 61.1 ± 12.9 72.2 61.6 42.4 41.2 22.5 2.7 31.1 8.6 27.2 74.2 87.4 68.9 65.7 ± 9.4 62.2 ± 13.0 LVEF, % 65.8 History of Hypertension, % 26.3 Diabetes Melitus, % 4.61 History of Stroke or TIA, % 36.8 Prior PCI, % 2.0 Prior CABG, % 27.0 Prior MI, % 61.2 History of Hyperlipidemia, % 46.7 History of Smoking, % 37.5 Insulin Dependent, % 77.3 Stable Angina, % 84.2 Angina, % 74.3 Male, % 64.4 ± 9.2 Age, years
    18. 18. QCA Analysis EuroSTAR II 30.18 ± 17.39 23.79 ± 16.33 1.99 ± 0.66 2.16 ± 0.65 59.41 ± 0.51 1.12 ± 0.37 15.12 ± 7.58 2.74 ± 0.51 CoStar NS 15.16 ± 7.69 Lesion Length, mm NS 60.93 ± 10.45 % DS, mm NS 1.05 ± 0.30 MLD, mm 8-Month Follow-up: Pre-Procedure: <0.0001 39.56 ± 15.04 % DS In-segment <0.0001 36.95 ± 16.93 % DS In-stent p-value UniStar 1.69 ± 0.52 1.77 ± 0.57 2.73 ± 0.48 0.0004 MLD In-segment, mm <0.0001 MLD In-stent, mm NS RVD, mm
    19. 19. 8-Month Binary Angiographic Restenosis 29/103 12/132 22/125 27/89 Primary Endpoint EuroSTAR II p=0.0002 p=0.0327 41.9% Reduction
    20. 20. Late Loss at 8 Months EuroSTAR II 0.81 ± 0.49 0.41 ± 0.48 0.64 ± 0.49 0.29 ± 0.50 p<0.0001 p<0.0001
    21. 21. MACE at 30-Days EuroSTAR II MACE defined as composite of TVR, new Q- or non-Q-wave MI attributed to target vessel, or cardiac death attributed to target vessel p=NS for all comparisons
    22. 22. MACE at 8 Months EuroSTAR II p=0.0214 p=0.0079 p=0.0465 p=NS p=NS p=NS
    23. 23. Stent Thrombosis: Definitions per Protocol <ul><li>Subacute: </li></ul><ul><ul><li>Abrupt vessel closure of the treatment site that results in clinical manifestations of ischemia and occlusion occurring after the patient left the cath lab but with 30 days of index procedure </li></ul></ul><ul><ul><ul><li>MI attributed to target vessel </li></ul></ul></ul><ul><ul><ul><li>ACS with angiographic evidence of thrombus </li></ul></ul></ul><ul><ul><ul><li>Death within 30 days that cannot be attributed to other obvious cause </li></ul></ul></ul><ul><li>Late: </li></ul><ul><ul><li>MI attributable to the target vessel, with angiographic documentation or thrombus or total occlusion at the target lesion 31-120 days post-procedure </li></ul></ul>EuroSTAR II
    24. 24. Stent Thrombosis EuroSTAR II p=NS for all comparisons
    25. 25. The four Studies with the Cobalt-Chromium CoStar ™ Stent releasing Paclitaxel 10µg/30 days (in-vitro) S. Silber Germany K. D. Dawkins UK M. W. Krucoff USA U. Kaul India Principal Investigator 0 0.7 0.6 0 Stent Thrombosis, % Randomized vs. BMS Registry Randomized vs. Taxus Registry Study Design n = 152 n = 145 n = 989 n = 40 Patients (Paclitaxel) 19.7 15.1 0.41 ± 0.48 17.6 15.12 ± 7.58 2.74 ± 0.51 EUROSTAR II 11.0 6.6 0.62 (0.64) 16.9 (18.7) 15.35 ± 6.48 2.77 ± 0.47 COSTAR II 10.9 ± 5.19 15.94 ± ? Lesion Length, mm 5.8 0,0 In-Segment RR, % 6 - 8 Months Angiographic Results: 8.3 7.5 MACE, % 2.8 1.8 TLR, % EUROSTAR I COSTAR I 0,55 ± 0,38 2.46 ± 0.41 8 - 12 Months Clinical Results: 0.28 ± 0.42 In-Stent Late Loss, mm 2.62 ± 0.54 RVD, mm
    26. 26. The four Studies with the Cobalt-Chromium CoStar ™ Stent releasing Paclitaxel 10µg/30 days (in-vitro) different release kinetics ? S. Silber Germany M. W. Krucoff USA Principal Investigator 0 0.6 Stent Thrombosis, % Randomized vs. BMS Randomized vs. Taxus Study Design n = 152 n = 989 Patients (Paclitaxel) 19.7 15.1 0.41 ± 0.48 17.6 15.12 ± 7.58 2.74 ± 0.51 EUROSTAR II 11.0 6.6 0.62 (0.64) 16.9 (18.7) 15.35 ± 6.48 2.77 ± 0.47 COSTAR II Lesion Length, mm In-Segment RR, % 6 - 8 Months Angiographic Results: MACE, % TLR, % 8 - 12 Months Clinical Results: In-Stent Late Loss, mm RVD, mm
    27. 27. The four Studies with the Cobalt-Chromium CoStar ™ Stent releasing Paclitaxel 10µg/30 days (in-vitro) S. Silber Germany M. W. Krucoff USA Principal Investigator 0 0.6 Stent Thrombosis, % Randomized vs. BMS Randomized vs. Taxus Study Design n = 152 n = 989 Patients (Paclitaxel) 19.7 15.1 0.41 ± 0.48 17.6 15.12 ± 7.58 2.74 ± 0.51 EUROSTAR II 11.0 6.6 0.62 (0.64) 16.9 (18.7) 15.35 ± 6.48 2.77 ± 0.47 COSTAR II Lesion Length, mm In-Segment RR, % 6 - 8 Months Angiographic Results: MACE, % TLR, % 8 - 12 Months Clinical Results: In-Stent Late Loss, % RVD, mm Angiography routinely performed at primary angiographic endpoint of 8 months Angiography 1 month after the primary clinical endpoint at 8 months
    28. 29. Conclusions <ul><li>EuroSTAR II is a positive trial, having reached its primary endpoint. </li></ul><ul><li>The CoStar ™ Paclitaxel-eluting stent had a significantly lower angiographic restenosis rate and a significantly lower late loss than the identically designed bare UniStar ™ . </li></ul><ul><li>With comparable vessel size and comparable lesion length in the TAXUS-IV trial, in-stent late loss of the CoStar ™ Paclitaxel-eluting stent in the EuroSTAR II trial was in the range of the Taxus stent. </li></ul><ul><li>TLR, TVR and MACE were also significantly reduced. </li></ul><ul><li>No early or late stent thromboses were seen with the CoStar ™ stent. </li></ul><ul><li>The reservoir technology combined with a completely absorbable polymer offers a great potential for further development using different drugs with modifiable optimization of release kinetics, specifically taylored to the patients’ needs. </li></ul>EuroSTAR II

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