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

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. Prognostic impact of on-treatment platelet reactivity in EXCELSIOR 0120240360 0 2 4 6 8 Log-RankP= 0.004 Days after PCI Death or myocardial infarction (%) RPA > 14% RPA ≤ 14% Trenk et al., J Am Coll Cardiol 2008; 51: 1925

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

5. 500 400 300 200 100 0 PRU value Post-PCI High-Dose 30 d 6 moPost-PCI30 d 6 mo Standard-Dose P = 0.98 P < 0.001 ITT population Persistently high reactivity @ 30 days: 62% vs 40%, p<0.001 Price et al., JAMA 2011; 305: 1097 N=1013N=940N=1105 N=1012N=944N=1109 Pharmacodynamic effect of high- and standard- dose Clopidogrel in patients with high OTR

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 major bleeding

7. “Standard Therapy” Clopidogrel MD 75 mg QD “Clopidogrel arm” Placebo LD Clopidogrel MD 75 mg QD + Prasugrel placebo “Prasugrel arm” Prasugrel LD 60 mg Prasugrel MD 10 mg QD + Clopidogrel placebo 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 Non-Responder Clinical Follow-up and blinded VerifyNow Assessment at 90 days, 180 days Primary Endpoint: 6 month CV Death or MI Yes No N ~6500 N = 1075 A Flow-chart TRIGGER-PCI Study Responder PRU > 208 N = 1075 B C N = 2,150  33% N = 4350 Non-interventional study (Registry)

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

11. 19.0% PRU >208 81.0% PRU ≤208 Frequency distribution of VerifyNow P2Y12 PRU after loading with Clopidogrel 600mg and 1st MD 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 Prasugrel N=212 Clopidogrel N=211 Residual platelet reactivity (PRU), median (IQR) 245 (225 - 273) 249 (225 - 277) Age, mean ± SD66 ± 866 ± 9 Male gender72%73% Body mass index (median) 29.129.6 Current smoker 16%14% Diabetes mellitus41%43% Hypertension 89% Prior myocardial infarction30%25% Prior PCI44%45% Prior CABG 12%14% Proton pump inhibitor21%22% Prior clopidogrel use 2%1%

14. Procedural characteristics of the randomized patients Prasugrel N=212 Clopidogrel N=211 Total no. of DES, mean±SD 1.9 ± 1.21.8 ± 1.1 Pts. with 1 stent51%50% 2 stents25%27% ≥ 3 stents 23% Stent length, mean±SD, mm 18.7 ± 7.918.5 ± 8.0 Stent diameter, mean±SD, mm 3.0 ± 0.5 Vessel type stented - Native artery95%97% - Saphenous vein graft2% - Arterial graft 1% Overlapping stents28%29%

15. Stents used in TRIGGER-PCI patients Prasugrel N=212 Clopidogrel N=211 Total no, of stents used395389 XIENCE V / PROMUS195(49%)207(53%) CYPHER119 (30%)101 (26%) ENDEAVOR49 (12%)24 ( 6%) TAXUS10 ( 3%)6 ( 2%) Endeavor Resolute / Resolute Integrity 8 ( 2%)31 ( 8%) Others14( 4%)20 (5%)

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

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

18. Summary of primary and secondary CEC-adjudicated efficacy endpoints Prasugrel N=212 Clopidogrel N=211 p HR (95% CI) Days on study treatment(median)174 - Primary composite efficacy EP: CV death or MI01(0.5%)- Key secondary efficacy EPs: MI 01(0.5%)- Rehospitalization for cardiac ischemic event 2(0.9%)4(1.9%) 0.992 0.99 ( 0.14-7.03 ) Urgent TVR 2(0.9%)1(0.5%)- Definite ST 00- Stroke 01(0.5%)- CV death 00- All cause death 01(0.5%) -

19. Summary of CEC-adjudicated bleeding events Prasugrel N=212 Clopidogrel N=211 p HR (95% CI) Key safety EP: Non-CABG TIMI Major Bleeding3 (1.4%)1 (0.5%)- Secondary bleeding events: Non-CABG TIMI fatal bleeding 00- Non-CABG TIMI life-threatening bleeding 01(0.5%)- Non-CABG TIMI major or minor bleeding 3(1.4%)2(1.0%) -.-. Non-CABG TIMI major, minor, or minimal bleeding 6(2.9%)4(1.9%) 0.516 1.52 ( 0.42-5.38)

20. Non-CABG TIMI major, minor or minimal bleeding Hazard Ratio 1.517 (95% CI, 0.428-5.376) p=0.516 Clopidogrel Prasugrel 0306090120150180210240 Days from randomization 0.0 0.5 1.5 1.0 2.0 2.5 3.0 3.5 4.0 Event rate, %

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. 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 Study organization

23. Principal Investigators F.-J. Neumann (Bad Krozingen, GER)R. Zimmermann (Pforzheim, GER) G. Schuler (Leipzig, GER)E. Dogu (Bremen, GER) M. Gawaz (Tuebingen, GER)M. Bergmann (Hamburg, GER) A. Kastrati (Munich, GER)C. Toma (Pittsburgh, PA, US) G. Richardt (Bad Segeberg, GER)S. V. Manoukian (Nashville, TN, US) J. Yu (Bad Berka, GER)T. J. Gluckman (Portland, OR, US) W. Jung (Villingen-Schwenningen, GER)D. J. Spriggs (Clearwater, FL, US) B. Witzenbichler (Berlin, GER)D. J. Angiolillo (Jacksonville, FL, US) H. Heuer (Dortmund, GER)J. C. Merritt (Rome, GA, US) S. Genth-Zotz (Mainz, GER)M. Haude (Neuss, GER) B. Goldmann (Hamburg,GER)V. Schaechinger (Fulda, GER) M. Moser (Freiburg, GER)H. Schuehlen (Berlin, GER) U. Sechtem (Stuttgart, GER)D. A. Purdy (Rapid City, SD, US) D. Boese (Essen, GER)S. Puri (Moline, IL, US) H. Mudra (Munich, GER)K. Garatt (New York, NY, US)