This document summarizes presentations from the 2007 Transcatheter Cardiovascular Therapeutics conference. Key findings include: - The ARMYDA-4 trial found that a 600mg clopidogrel loading dose prior to PCI in patients on chronic clopidogrel therapy reduced the risk of death, MI, or TVR at 30 days compared to placebo. - The HORIZONS AMI trial found that using bivalirudin monotherapy during PCI for AMI reduced major bleeding at 30 days compared to unfractionated heparin plus a GP IIb/IIIa inhibitor, with similar rates of net adverse clinical events. - Data from the EVENT registry showed declining rates of bleeding complications and stent

1. ACS Critical Pathways 2007 Teleconferences This activity is supported by an educational grant from the Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership. This activity is co-provided by the Network for Continuing Medical Education and EduPro Resources LLC. October 31, 2007

2. Faculty Gregg C. Fonarow, MD Eliot Corday Professor of Medicine and Cardiovascular Science Director, Ahmanson-UCLA Cardiomyopathy Center UCLA Division of Cardiology UCLA Medical Center Los Angeles, California

3. The Network for Continuing Medical Education and EduPro Resources LLC require that CME/CNE faculty disclose, during the planning of an activity, the existence of any personal financial or other relationships they or their spouses/partners have with the commercial supporter of the activity or with the manufacturer of any commercial product or service discussed in the activity. Disclosure Statement

4. Faculty Disclosure Statement Gregg C. Fonarow, MD , has served as a consultant to and has received research support and honoraria from Bristol-Myers Squibb Company, GlaxoSmithKline, Merck & Co., Inc., Pfizer Inc, and sanofi-aventis. Deborah Murphy reports no such relationships. The staff of NCME reports no such relationships.

5. Report From Transcatheter Cardiovascular Therapeutics (TCT) 2007 Gregg C. Fonarow, MD

6. Polling Question #1 Where do you currently stand on using DES? In light of SCAAR and other recent data, my use of DES is increasing since earlier in 2007 In light of the GRACE Registry and other recent data, my use of DES is decreasing since earlier in 2007 My practice has not changed since earlier in 2007 with regard to DES

7. Highlights From TCT 2007 ARMYDA-4: 600 mg clopidogrel loading dose prior to PCI in patients on chronic clopidogrel therapy ARMYDA-5: antiplatelet therapy for reduction of myocardial damage during angioplasty HORIZONS AMI: bivalirudin vs heparin + GP IIb/IIIa inhibitors during primary angioplasty in AMI SPIRIT III: 1-year follow-up stent data Endeavor IV: 9- and 12-months results, Endeavor vs TAXUS stents EVENT Registry: Implications of changing stent practice from 2004 to 2006 SCAAR: Swedish Coronary Angiography and Angioplasty Registry NY State Database and STENT Registry: Comparison of DES vs BMS

8. Percentage 7 8 P =.96 Patti G, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. ARMYDA-4: Composite Primary End Point of 30-day Death, MI, TVR 0 3 6 9 12 Placebo 600 mg clopidogrel reload

9. Patti G, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. 7 8 Percentage 600 mg clopidogrel reload Placebo ARMYDA-4: Individual Events at 30 Days 0 2 4 6 8 10 Death MI TVR

10. Patti G, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. ARMYDA-4: Bleeding Rates 600 mg clopidogrel reload Placebo 4 4 0 0 Percentage 0 2 4 6 Major bleeding Minor bleeding

11. ARMYDA-5: Study Design Patients scheduled for angiography randomized to: 600 mg clopidogrel loading dose (n=174) 4 to 8 hours prior to angiography or Loading with clopidogrel in the cath lab once the coronary anatomy was defined and PCI was definite (n=176) Not included: 35 patients who underwent CABG and 53 patients treated with medical therapy Primary end point: death, MI, or TVR at 30 days 44% of patients had NSTEMI; 36% had a prior MI Di Sciascio G, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.

12. ARMYDA-5: Results PRUs = platelet reactivity units. Di Sciascio G, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. NS 5% 4% Minor bleeding .04 .005 272 PRUs 245 PRUs 241 PRUs 186 PRUs Platelet reactivity at PCI At 2 hours: .56 11% 8% Death, MI, or TVR at 30 days P Value Cath-lab treatment Pretreatment

13. HORIZONS AMI: 2 Primary End Points at 30 Days 1) Net Adverse Clinical Events 2) Major Bleeding (non-CABG) Intracranial bleeding Intraocular bleeding Retroperitoneal bleeding Access site bleed requiring intervention/surgery Hematoma ≥5 cm Hgb  ≥3 g/dL with an overt source Hgb  ≥4 g/dL w/o overt source Reoperation for bleeding Blood product transfusion and Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.

14. HORIZONS AMI: 2 Primary End Points at 30 Days (cont) = or All-cause death Reinfarction Ischemic TVR Stroke Major adverse cardiovascular events (major secondary end point) Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. 1) Net Adverse Clinical Events 2) Major Bleeding (non-CABG)

15. HORIZONS AMI: Study Drugs a 97.7% and 7.5% during PCI; b For giant thrombus or refractory no reflow after PCI. CCL = cardiac catheterization laboratory. Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. UFH + GP IIb/IIIa (N=1802) Bivalirudin (N=1800) UFH prerandomization 65.6% 65.6% Antithrombin in CCL - UFH 98.9% 4.1% - Bivalirudin 0.4% 96.9% - Peak ACT 264 [228, 320] 357 [300, 402] GP IIb/IIIa in CCL 94.5% a 7.2% a - Bail-out per protocol b - 4.4% - Abciximab 49.9% 4.0% - Eptifibatide 44.4% 3.1% - Tirofiban 0.2% 0.1%

16. Primary Outcome Measures (ITT) a Not related to CABG; b MACE = All-cause death, reinfarction, ischemic TVR or stroke. Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. Diff = 0.0% [-1.6, 1.5] RR = 0.99 [0.76, 1.30] P sup = 1.00 Diff = -3.3% [-5.0, -1.6] RR = 0.60 [0.46, 0.77] P NI ≤ .0001 P sup ≤ .0001 Diff = -2.9% [-4.9, -0.8] RR = 0.76 [0.63, 0.92] P NI ≤ .0001 P sup = .006 1  end point 1  end point 0 5 10 20 15 12.1 9.2 8.3 4.9 5.5 5.4 Net adverse clinical events Major bleeding a MACE b 30-day event rates (%) Bivalirudin monotherapy (N=1800) Heparin + GP IIb/IIIa inhibitor (N=1802)

17. 30-day Net Adverse Clinical Events Number at risk Bivalirudin 1800 1660 1633 1626 1620 1607 1544 Heparin + GP IIb/IIIa 1802 1635 1591 1578 1569 1552 1482 Primary End Point Net adverse clinical events (%) Time in Days 12.2% 9.3% HR [95%CI] = 0.75 [0.62, 0.92] P =.006 Heparin + GP IIb/IIIa inhibitor (n=1802) Bivalirudin monotherapy (n=1800) Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.

18. 30-day Major Bleeding (non-CABG) Number at risk Bivalirudin 1800 1697 1675 1668 1664 1653 1590 Heparin + GP IIb/IIIa 1802 1651 1617 1606 1598 1581 1511 Primary End Point Major bleeding (%) Time in Days 8.4% 5.0% HR [95%CI] = 0.59 [0.45, 0.76] P <.0001 Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. Heparin + GP IIb/IIIa inhibitor (n=1802) Bivalirudin monotherapy (n=1800)

19. 30-day Bleeding End Points a Primary end point; b life threatening. Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. UFH + GP IIb/IIIa (N=1802) Bivalirudin (N=1800) P Value Protocol Major, non-CABG a 8.3% 4.9% <.0001 Protocol Major, All 10.8% 6.8% <.0001 Protocol Minor 15.4% 8.6% <.0001 Blood transfusion 3.5% 2.1% .01 TIMI Major 5.0% 3.1% .003 TIMI Minor 4.6% 2.8% .008 TIMI Major or Minor 9.6% 5.9% <.0001 GUSTO LT b or Severe 0.6% 0.4% .65 GUSTO Moderate 5.0% 3.1% .003 GUSTO LT or Sev or Mod 5.6% 3.5% .003

20. 30-day MACE Components a a CEC adjudicated. Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. UFH + GP IIb/IIIa (N=1802) Bivalirudin (N=1800) P Value Death 3.1% 2.1% .058 - Cardiac 2.9% 1.8% .035 - Noncardiac 0.2% 0.3% .75 Reinfarction 1.8% 1.8% .90 - Q wave 1.2% 1.4% .66 - Non – Q wave 0.7% 0.4% .50 Ischemic TVR 1.9% 2.6% .18 - Ischemic TLR 1.8% 2.5% .14 - Ischemic remote TVR 0.3% 0.3% 1.0 Stroke 0.6% 0.7% .69

21. SPIRIT III: MACE Through 365 Days MACE = cardiac death, MI, or ischemia-driven TLR. Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. 0 3 6 12 9 MACE (%) 0 90 180 270 365 Days 9.9% 5.8% TAXUS XIENCE HR = 0.57 [0.36 – 0.90 ] P logrank = .01 Number at risk XIENCE 669 651 642 626 614 TAXUS 332 312 309 292 287

22. Endeavor IV: Primary End Point Result at 9 Months Leon MB, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. P for Noninferiority <.001 ∆ = 3.8% 6.6% 7.2% Endeavor (n=50/758) Taxus (n=54/759) TVF Rate Target Vessel Failure

23. a Day 83, 145, 171. Leon MB, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. Endeavor IV: Clinical Events at 12 Months .267 9.4 (70 7.7 (58) TVF – % (#) 1.000 6.6 (49) 6.5 (49) MACE – % (#) .753 6.7 (50) 6.3 (47) TVR – % (#) .085 4.2 (31) 2.5 (19) TVR (non-TL) – % (#) .228 3.2 (24) 4.5 (34) TLR – % (#) .250 0 0.4 a (3) 31-360 days .625 0.1 (1) 0.4 (3) 0-30 days .124 0.1 (1) 0.8 (6) Stent Thrombosis (all) – % (#) .260 3.1 (23) 2.1 (16) Death (cardiac) + MI (all) – % (#) .131 2.4 (18) 1.3 (10) Non – Q wave 1.000 0.1 (1) 0.3 (2) Q Wave .208 2.6 (19) 1.6 (12) MI (all) – % (#) 1.000 0.5 (4) 0.5 (4) Cardiac 1.000 1.1 (8) 1.1 (8) Death (all) – % (#) P Value Taxus n=741 Endeavor n=749

24. EVENT Registry: Bleeding Complications Kleiman N, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. 0.6 0.0% 2.0% 4.0% 6.0% TIMI Major 0.2 0.2 1.0 0.8 0.5 3.5 2.0 1.8 5.2 4.1 3.4 TIMI Minor Transfusion Any bleed or transfusion Not mutually exclusive WAVE 2 WAVE 1 WAVE 3

25. EVENT Registry: Adjudicated Stent Thrombosis From Procedure to 1 Year Follow-up Kleiman N, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. 2.2% 0% WAVE 2 WAVE 1 WAVE 3 P = .046 P = .027 (Logistic regression) In Hospital 6 Months 12 Months Wave 2 is ARC Probable ; Wave 3 is ARC Definite or Probable Wave 1 to Wave 3 1.1 0.8 0.9 1.9 1.0 1.2 (Log rank) 0.4 0.2 0.1

26. Carlsson J, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. SCAAR: Adjusted Death/MI Total Cohort BMS 10049 9529 9343 8112 6742 5265 3486 1892 5 DES 6523 6222 6069 4428 2947 1868 908 322 0 BMS 9434 8424 8223 6896 5431 4012 2433 1285 2 DES 6165 5673 5512 3792 2508 1525 780 287 0 0.25 0.20 0.15 0.10 0.05 0.00 0 1 2 3 4 Cumulative risk of death or MI RR: 1.03 (0.93, 1.15) BMS DES On label use N=17,664 Time (years) 0.25 0.20 0.15 0.10 0.05 0.00 0 1 2 3 4 Cumulative risk of death or MI RR: 0.96 (0.88, 1.06) BMS DES Off label use N=16,866 Time (years)

27. Carlsson J, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. SCAAR: Restenosis at Clinically Driven Re-angiography BMS 3987 3794 3698 3079 2188 1140 50 0 0 DES 3235 3142 3080 2354 1389 630 21 0 0 BMS 3586 3291 3202 2649 1812 909 24 0 0 DES 2158 2034 1966 1407 846 339 11 0 0 0.10 0.08 0.06 0.04 0.02 0.00 0 1 2 3 4 Cumulative risk of death or MI RR: 0.39 (0.3, 0.51) BMS DES On label use N=12,186 Time (years) 0.10 0.08 0.06 0.04 0.02 0.00 0 1 2 3 4 Cumulative risk of death or MI RR: 0.66 (0.5, 0.88) BMS DES Off label use N=9,155 Time (years) RRR 60% ARR 4% RRR 40% ARR 2.5%

28. NY State Database and STENT Registry Brodie BR, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. Clinical Outcomes of DES vs BMS in the New York Database 2.98 ( P <.001) 2.23 ( P <.001) 1.17 1.17 Adjusted HR Second analysis of significant predictors of mortality (n=4,983) 2.30 1.85 1.19 1.19 Adjusted HR for BMS/DES 2.17 1.77 1.25 1.26 Unadjusted HR for BMS/DES 9.4% 6.1% 7.8% 4.8% DES (n=6,384) 16.6% 13.5% 9.2% 5.6% BMS (n=7,834) Rate of subsequent TVR Rate of subsequent TLR MI or death Mortality 2-year data

29. NY State Database and STENT Registry Brodie BR, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC. Clinical Outcomes of DES vs BMS in the STENT Registry 35.4% 2% Year 1-2 19% 9% 30 days to 1 year 45.6% 57.7% Timing of stent thrombosis <30 days 16.1% 24.7% MACE 9.1% 16% Death or MI 8.8% 11.9% TVR 4.1% 6.7% MI 5.7% 11% Death DES (n=5,996) BMS (n=1,359) 2-year data

30. Featured Institution Paoli Hospital Paoli, Pennsylvania

31. Polling Question 1) We are currently on the same item 2) We have since moved to the next checkbox on the checklist 3) We have progressed by more than one item on the checklist 4) ACS pathways are up-to-date and regularly followed If you participated in a previous teleconference, how much progress have you made since then? (Please refer to the checklists on the next 3 slides.)

32. Progress Checklist: Immediate Goals  Assemble team and set up meeting of working group  Develop draft pathways  Circulate pathways to all cardiology, ED, and CV nursing staff for comments  Circulate discharge plan and other tools to all cardiology, ED, and CV nursing staff for comments

33. Progress Checklist: Short-term Goals/Activities  Finalize critical pathways  Launch critical pathways  Circulate memo  Grand rounds/conference: Cardiology/IM  Grand rounds/conference: Emergency Department  Grand rounds/conference: Nursing

34. Progress Checklist: Long-term Goals/Activities  Monitor data: which registry?  NRMI  AHA Get With The Guidelines  ACC National Cardiovascular Data Registry  CRUSADE  GRACE  REACH  Other

35. Question-and-Answer Session

36. Concluding Remarks Gregg C. Fonarow, MD Next Program Christopher P. Cannon, MD Wednesday, November 14, 2007 12:00 Noon Eastern Time (9:00 AM Pacific Time) Report From the American Heart Association (AHA) Scientific Sessions 2007