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Dietmar Trenk, PhD On behalf of the TRIGGER-PCI Investigators

Primary Results of T esting platelet R eactivity I n patients under G oing elective stent placement on clopidogrel to G uide alternative th E rapy with p R asugrel TRIGGER-PCI Study. TCT 2011. Dietmar Trenk, PhD On behalf of the TRIGGER-PCI Investigators. Disclosures.

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Dietmar Trenk, PhD On behalf of the TRIGGER-PCI Investigators

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  1. Primary Results of Testing platelet Reactivity In patients underGoing elective stent placement on clopidogrel to Guide alternative thErapy with pRasugrel TRIGGER-PCI Study TCT 2011 Dietmar Trenk, PhD On behalf of the TRIGGER-PCI Investigators

  2. Disclosures Consulting fees/honoraria: Eli Lilly, Daiichi Sankyo, sanofi-aventis, AstraZeneca Speaker Honoraria: Eli Lilly, Daiichi Sankyo, sanofi-aventis, AstraZeneca Off-label use of prasugrel and VerifyNow P2Y12 test will be discussed in this presentation

  3. RPA > 14% RPA ≤ 14% Prognostic impact of on-treatment platelet reactivity in EXCELSIOR 8 6 Log-Rank P = 0.004 Death or myocardial infarction (%) 4 2 0 0 120 240 360 Days after PCI Trenk et al., J Am Coll Cardiol 2008; 51: 1925

  4. High dose vs. standard dose Clopidogrel:Primary Endpoint: CV death, MI, stent thrombosis n=1109 n=1105 Price et al., JAMA 2011; 305: 1097

  5. Pharmacodynamic effect of high- and standard-dose Clopidogrel in patients with high OTR Standard-Dose High-Dose 500 P = 0.98 P < 0.001 400 Persistently high reactivity @ 30 days: 62% vs 40%, p<0.001 PRU value 300 200 100 0 N=1105 N=1013 N=940 N=1109 N=1012 N=944 6 mo 6 mo Post-PCI 30 d Post-PCI 30 d ITT population Price et al., JAMA 2011; 305: 1097

  6. Study objective … to assess whether the outcome of patients with high on-clopidogrel platelet reactivity after elective PCI with drug-eluting stents can be improved by switching from clopidogrel to prasugrel. Primary efficacy endpoint: Cardiovascular death or myocardial infarction Key safety endpoint: Non-CABG TIMI majorbleeding

  7. Flow-chart TRIGGER-PCI Study Successful PCI with DES without major complication and NO GPIIb/IIIa use Post-PCI VerifyNow P2Y12 Assay (PRU) 2 - 7 hours after MD of clopidogrel 75 mg at day 1 post-PCI N ~6500 PRU > 208 No Yes Responder Non-Responder B C A N = 1075 N = 1075 N = 4350 “Prasugrel arm” Prasugrel LD 60 mg Prasugrel MD 10 mg QD + Clopidogrel placebo “Clopidogrel arm” Placebo LD Clopidogrel MD 75 mg QD + Prasugrel placebo “Standard Therapy” Clopidogrel MD 75 mg QD Non-interventional study (Registry) N = 2,150  33% Clinical Follow-up and blinded VerifyNow Assessment at 90 days, 180 days Primary Endpoint: 6 month CV Death or MI

  8. Key inclusion and exclusion criteria Major inclusion criteria Successful DES-PCI in patients with stable CAD and clinical indication for PCI Clopidogrel 600-mg LD between 24 hours before, and the time of PCI + 75-mg MD in the morning after PCI. Major exclusion criteria Patients with STEMI / NSTEMI Patients with known major complications after PCI

  9. 6-month incidence of the composite endpoint of cardiovascular death or MI (including minor infarctions with elevated troponin) expected as 4.7%. Randomization of 2,150 patients to provide 93% power to detect a 50 % relative risk reduction on prasugrel. Sample size and power calculation

  10. Disposition of patients in TRIGGER-PCI 3,525 patients screened 33 No test result 3,492 VerifyNow testing 209 Invalid test result PRU >208? No 2,658 pts. with PRU ≤208 Yes 625 patients with PRU >208 202 patients declined 423 patients randomized 212 prasugrel 211 clopidogrel 210 received ≥1 dose clopidogrel 210 received ≥1 dose prasugrel 74 study discontinuations 15 Subject decision 1 Consent revoked 58 Early termination of study 73 study discontinuations 9 Subject decision 4 Consent revoked 60 Early termination of study 136 completed study 137 completed study

  11. Frequency distribution of VerifyNow P2Y12 PRU after loading with Clopidogrel 600mg and 1st MD 81.0% PRU ≤208 19.0% PRU >208 Total n=3,283 patients

  12. Early termination of TRIGGER-PCI at March 18, 2011 236 patients completed 6 months follow-up Only 1 clinical endpoint (peri-procedural MI) observed → rate 0.4% Upper 95 %-confidence limit 1.25 %

  13. Baseline demographic and clinical characteristics of the randomized patients

  14. Procedural characteristics of the randomized patients

  15. Stents used in TRIGGER-PCI patients

  16. Platelet reactivity by VerifyNow P2Y12 assay:Prasugrel 10mg QD vs. Clopidogrel 75mg QD ITT - population Median with interquartile range; 10-90% percentile

  17. 70.8% 70.4% 5.8% 5.9% Proportion of pts. with high on-treatment platelet reactivity by VerifyNow P2Y12 assay (PRU >208)

  18. Summary of primary and secondary CEC-adjudicated efficacy endpoints

  19. Summary of CEC-adjudicated bleeding events

  20. Non-CABG TIMI major, minor or minimal bleeding 4.0 3.5 3.0 Prasugrel 2.5 Event rate, % 2.0 Clopidogrel 1.5 Hazard Ratio 1.517 (95% CI, 0.428-5.376) p=0.516 1.0 0.5 0.0 0 30 60 90 120 150 180 210 240 Days from randomization

  21. Summary and conclusion: Effectiveness of Prasugrel vs Clopidogrel after elective PCI • High on-clopidogrel platelet reactivity (>208 PRU by VerifyNow P2Y12 test) was observed less frequently than expected. • Compared with standard-dose clopidogrel 75 mg QD, prasugrel 10 mg QD substantially decreased platelet reactivity in patients with high on-clopidogrel platelet reactivity after elective PCI. • Given the low event rate in elective PCI patients without peri-procedural complications it was not possible to assess the risk – benefit ratio with prasugrel treatment. Therefore, the study was terminated prematurely for futility.

  22. Study organization Trial Leadership: Franz-Josef Neumann (Chair), Dietmar Trenk, Adnan Kastrati, Meinrad Gawaz, Gregg W. Stone (US PI), Dominick J. Angiolillo, Joseph A. Jakubowski Sponsor: Eli Lilly and Company, Daiichi Sankyo Co., Ltd. Data Center and Site Management: Quintiles Data Safety and Monitoring Board: Hanjörg Just (chair), Jochen Senges, Kurt Ulm

  23. Principal Investigators

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