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Prasugrel Compared to Clopidogrel in Patients with Acute Coronary Syndromes Undergoing PCI with Stenting: the TRITON -

STENT ANALYSIS. Prasugrel Compared to Clopidogrel in Patients with Acute Coronary Syndromes Undergoing PCI with Stenting: the TRITON - TIMI 38 Stent Analysis .

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Prasugrel Compared to Clopidogrel in Patients with Acute Coronary Syndromes Undergoing PCI with Stenting: the TRITON -

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  1. STENT ANALYSIS Prasugrel Compared to Clopidogrel in Patients with Acute Coronary Syndromes Undergoing PCI with Stenting: the TRITON - TIMI 38 Stent Analysis Stephen D. Wiviott, Elliott M. Antman, Ivan Horvath, Matyas Keltai, Jean-Paul R. Herrman, Frans van de Werf, William Downey, Benjamin M. Scirica, Sabina A. Murphy, Carolyn H. McCabe, Eugene Braunwald SCAI – ACCi2 2008Chicago, Illinois Disclosure Statement: The TRITON-TIMI 38 trial was supported by a research grant to the Brigham and Women’s Hospital from Daiichi Sankyo Co. Ltd and Eli Lilly & Co.

  2. Main Trial Design STENT ANALYSIS ACS (STEMI or UA/NSTEMI) & Planned PCI N= 13,608 ASA Double-blind CLOPIDOGREL 300 mg LD/ 75 mg MD PRASUGREL 60 mg LD/ 10 mg MD Duration of therapy: 6-15 months 1o endpoint: CV death, MI, Stroke 2o endpoint: Stent Thrombosis Safety endpoints: TIMI major bleeds, Life-threatening bleeds Wiviott SD, Antman EM et al AHJ 2006

  3. Trial Organization STENT ANALYSIS Trial Leadership: TIMI Study Group Eugene Braunwald,Chairman, Elliott M. Antman, PI, Carolyn H. McCabe, Director, Stephen D. Wiviott, Gilles Montalescot, Sabina A. Murphy, Susan McHale Sponsors: Daiichi Sankyo and Eli Lilly J. Anthony Ware, Jeffrey Riesmeyer, William Macias, James Croaning, Govinda Weerakkody, Francis Plat, Tomas Bocanegra Data Center and Site Management: Quintiles Inc Data Safety Monitoring Board David Williams (Chair) , Christophe Bode, Spencer King, Ulrich Sigwart, David DeMets

  4. Main Trial: Primary Results 15 Clopidogrel HR 0.81(0.73-0.90)P=0.0004 12.1 CV Death / MI / Stroke 9.9 10 Prasugrel Endpoint (%) 5 TIMI Major NonCABG Bleeds Prasugrel 2.4 HR 1.32(1.03-1.68)P=0.03 1.8 Clopidogrel 0 0 30 60 90 180 270 360 450 Days Wiviott SD, Braunwald E, McCabe CH et al NEJM2007

  5. Goals of Stent Analysis STENT ANALYSIS • To compare the efficacy and safety of PRASUGREL and CLOPIDOGREL in 12,844 patients with at least one stent as part of the index procedure with respect to: • Stent Thrombosis (ARC definitions) • Ischemic Events, Bleeding • Overall and stratified by stent type received

  6. Patient Population STENT ANALYSIS Randomized 13,608 Stent Placed 12,844 (94%) BMS Only 6461 (47%) DES Only 5743 (42%) Both BMS/DES 640 (5%) PES Only 2766 (20%) SES Only 2454 (18%) Other/Mixed 523 (4%)

  7. Baseline Characteristics STENT ANALYSIS

  8. Key Efficacy, Safety EP:Stratified by Stent Type STENT ANALYSIS CVD/MI/CVA Non-CABG TIMI Major Bleeding HR 0.80 (0.69-0.93) p=0.003 HR 0.82 (0.69-0.97) p=0.02 CLOPIDOGREL PRASUGREL % of Subjects HR 1.37 (0.95-1.99) p=0.09 HR 1.19 (0.83-1.72) p=0.34 N=6461 N=5743

  9. ARC ST Definitions STENT ANALYSIS Blinded CEC review of using source documents incl imaging reports: Definite: total occlusion w/in or < 5 mm of the stent or thrombus w/in or< 5 mm of the stent AND a clinical syndrome <48 h. Probable: unexplained death < 30 days or MI in stented territory w/o angiographic confirmation ST AND w/o alternative cause Possible: unexplained death > 30 days following stenting Early: 0 – 30 days after randomization Late > 30 days after randomization (landmark analysis) Based on ARC Definitions Mauri L et al NEJM 2007

  10. Mortality During Follow up (%) Post-Stent Thrombosis Death Following ST STENT ANALYSIS HR 13.1 (9.8 – 17.5) P<0.0001 % of Subjects N=210 N=12634

  11. Definite/Probable ST: Any Stent (N=12844) STENT ANALYSIS 2.35% 2.5 HR 0.48 [0.36-0.64] P<0.0001 2 CLOPIDOGREL 52% 1.5 % of Subjects 1.13% 1 PRASUGREL 1 year: 1.06 vs 2.15% HR 0.48 [0.36-0.65], P<0.0001 0.5 0 0 50 100 150 200 250 300 350 400 450 DAYS

  12. Definite/Probable ST: Any Stent (N=12844) STENT ANALYSIS EARLY ST LATE ST HR 0.41 [0.29-0.59] P<0.0001 HR 0.60 [0.37-0.97] P=0.03 CLOPIDOGREL PRASUGREL 1.56% % of Subjects 59% 0.82% 40% 0.64% 0.49% DAYS

  13. Stent Thrombosis By ARC Category (N=12844) STENT ANALYSIS CLOPIDOGREL PRASUGREL DEF/PROB/POSS HR 0.56 (0.43-0.73) P<0.0001 DEF/PROB HR 0.48 (0.36-0.64) P<0.0001 DEFINITE HR 0.42 (0.31-0.59) P<0.0001 % of Subjects

  14. Stent Thrombosis Subgroups STENT ANALYSIS PRAS CLOP RISK (%) 1.6 2.8 42% 1.0 2.2 57% 1.4 2.9 53% 0.9 1.9 52% 1.1 2.2 50% 1.4 4.6 69% 1.1 2.1 51% 1.1 3.9 70% 1.2 2.1 45% 0.8 3.4 75% 0.9 2.0 54% 1.3 2.6 51% 2.0 3.6 48% 0.9 2.0 55% 1.8 3.4 44% 1.0 2.2 54% 0.9 2.3 61% 1.2 2.4 50% PRASUGREL BETTER CLOPIDOGREL BETTER

  15. Definite/Probable ST: DES Only (N=5743) STENT ANALYSIS 2.31% HR 0.36 [0.22-0.58] P<0.0001 CLOPIDOGREL 64% % of Subjects 0.84% PRASUGREL 1 year: 0.74% vs 2.05% HR 0.35 [0.21-0.58], P<0.0001 DAYS

  16. Definite/Probable ST: DES Only (N=5743) STENT ANALYSIS EARLY ST LATE ST HR 0.29 [0.15-0.56] P=0.0001 HR 0.46 [0.22-0.97] P=0.04 CLOPIDOGREL PRASUGREL 1.44% % of Subjects 0.91% 71% 54% 0.42% 0.42% DAYS

  17. Stent Thrombosis DES SubtypesTrial Duration STENT ANALYSIS CLOPIDOGREL PRASUGREL Sirolimus Only HR 0.33 (0.15-0.73) p=0.004 Paclitaxel Only HR 0.33 (0.16-0.68) p=0.002 % of Subjects 67% 67% N=2766 N=2454

  18. Definite/Probable ST: BMS Only (N=6461) STENT ANALYSIS 2.41% HR 0.52 [0.35-0.77] P=0.0009 CLOPIDOGREL 48% % of Subjects 1.27% PRASUGREL 1 year: 1.22 vs 2.27% HR 0.53 [0.36-0.79], P=0.0014 DAYS

  19. Definite/Probable ST: BMS Only (N=6461) STENT ANALYSIS EARLY ST LATE ST HR 0.45 [0.28-0.73] P=0.0009 HR 0.68 [0.35-1.31] P=0.24 CLOPIDOGREL 1.66% PRASUGREL % of Subjects 55% 0.78% 32% 0.75% 0.53% DAYS

  20. Summary STENT ANALYSIS • Intensive antiplatelet therapy with PRASUGREL in stented patients compared to CLOPIDOGREL: • Substantial reduction in ST: • Regardless of stent type or ST definition • Early and Late • A broad range of clinical/procedural characteristics • Fewer ischemic events, more major bleeding

  21. Balance of Efficacy and Safety (Stented Population) STENT ANALYSIS Stent Thrombosis CVD/MI/CVA w/o ST Events per 1000 patients treated

  22. Conclusions/Implications STENT ANALYSIS www.thelancet.com • Stent Thrombosis is a rare, but devastating complication of PCI associated with a high mortality. Efforts to reduce ST have focused on compliance w/ and duration of ASA/clopidogrel • Our data indicate that an agent w/ more rapid, consistent, and greater inhibition of platelet aggregation (prasugrel) results in major reductions (~50%) in ST across a broad array of clinical procedural characteristics

  23. STENT ANALYSIS

  24. Net Clinical Benefit Clinical Endpoints STENT ANALYSIS HR 0.84 (0.72-0.98) p=0.025 HR 0.88 (0.77-1.01) p=0.07 HR 0.86 (0.77-0.95) p=0.002 % of Subjects N=6461 N=12844 N=5743

  25. Primary EP (D/MI/CVA) Not Related to ST STENT ANALYSIS HR 0.85, P=0.005 10.3% 15% CLOPIDOGREL 8.7% % of Subjects PRASUGREL DAYS

  26. Key Efficacy, Safety EP:Stratified by Stent Type STENT ANALYSIS CVD/MI/CVA Major Bleeding HR 0.82 (0.69-0.97) p=0.02 HR 0.80 (0.69-0.93) p=0.003 HR 0.81 (0.72-0.90) p=0.0001 CLOPIDOGREL PRASUGREL HR 1.27 (0.99-1.63) p=0.06 HR 1.37 (0.95-1.99) p=0.09 HR 1.19 (0.83-1.72) p=0.34 N=6461 N=12844 N=5743

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