1 / 26

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 .

Olivia
Download Presentation

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

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  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

More Related