The document summarizes a teleconference discussing trials presented at the 2006 American Heart Association Scientific Sessions. It highlights the merging of two registries to form the NCDR-ACTION registry, and a national initiative to reduce door-to-balloon times for primary PCI to under 90 minutes. Trial results showed increased mortality with delays to PCI and that the advantage of PCI over fibrinolysis decreases with longer PCI-related delays.

1. CVD Critical Pathways Group 2006 Teleconferences This activity is supported by an educational grant from the Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership. December 6, 2006

5. Highlights From the 2006 American Heart Association Scientific Sessions Gregg C. Fonarow, MD

9. D2B: Strategies Associated With a Significant Reduction in Door-to-Balloon Time * P <.05 for all. Bradley EH, et al. N Engl J Med. 2006. November 13. [Epub ahead of print]. 8.6 Having staff in ED and cath lab use and receive real-time feedback 14.6 Having an attending cardiologist always on site 19.3 Expecting staff to arrive at cath lab within 20 minutes after page 15.4 Having the ED activate the cath lab while patient still en route 13.8 Having a single call to a central page operator activate cath lab 8.2 Having emergency medicine physicians activate the cath lab Mean reduction in door-to-balloon time (min)* Strategy

10. NRMI 2,3,4 452,544 Reperfusion Eligible STEMI Patients 1963 Hospitals Transfer Out Patients n=119,235 Missing Time Intervals n=13,137 Did Not Receive PCI or Fibrinolytic Therapy as Initial Reperfusion n=89,524 Study Population 192,509 Patients 645 Hospitals 230,648 Patients 1860 Hospitals ≥ 20 STEMI Patients Treated Treatment of ≥10 Patients With Primary PCI and ≥10 Patients With Fibrinolytic Therapy © CM Gibson 2006. Pinto DS, et al. Circulation . 2006;114:2019-2025. Adapted with permission from clinicaltrialresults.org. Implications of Hospital Delays for Selection of Reperfusion Strategy in STEMI

11. Mortality Increases With Increasing PCI-Related Delay © CM Gibson 2006. Pinto DS, et al. Circulation . 2006;114:2019-2025. Adapted with permission from clinicaltrialresults.org. PCI-Related Delay (door-to-balloon–door-to-needle time) (min) In-Hospital Mortality (%) For every 30-minute delay, mortality increases 10% 12 10 8 6 4 2 0 0 20 40 60 80 100 120 140 160 180 200

12. Advantage of PCI Compared With Fibrinolyisis Decreases as PCI-Related Delay Increases © CM Gibson 2006. Pinto DS, et al. Circulation . 2006;114:2019-2025. Adapted with permission from clinicaltrialresults.org. Odds of Death With Fibrinolysis PCI-Related Delay (door-to-balloon–door-to-needle time) (min) PCI Better Fibrinolysis Better 12 1.5 1.25 1.0 0.8 0.5 60 75 90 105 114 135 150 165 180

13. Time at Which PCI Loses Superiority in Survival Over Fibrinolysis Varies by Patient Risk © CM Gibson 2006. Pinto DS, et al. Circulation . 2006;114:2019-2025. Adapted with permission from clinicaltrialresults.org. 183 min Met goal without transfer: 100.0% Met goal with transfer: 100.0% (n=10,614 pts; n=191 hospitals) 142 min Met goal without transfer: 98.1% Met goal with transfer: 97.1% (n=3,739 pts; n=91 hospitals) 103 min Met goal without transfer: 89.1% Met goal with transfer: 82.2% (n=16,119 pts; n=244 hospitals) 50 min Met goal without transfer: 7.9% Met goal with transfer: 11.9% (n=5,296 pts; n=117 hospitals) 121+ 154 min Met goal without transfer: 99.8% Met goal with transfer: 100.0% ( n=20,424 pts; n=271 hospitals) 109 min Met goal without transfer: 94.1% Met goal with transfer: 92.8% (n=9,812 pts; n=180 hospitals) 56 min Met goal without transfer: 20.2% Met goal with transfer: 17.3% (n=19,517 pts; n=269 hospitals) 39 min Met goal without transfer: 2.6% Met goal with transfer: 3.6% (n=19,517 pts; n=269 hospitals) 0-120 Age ≥65 years and Non-anterior Infarction Age ≥65 years and Anterior Infarction Age <65 years and Non-anterior Infarction Age <65 years and Anterior Infarction Pre-hospital Delay (Min)

15. RIKS-HIA Registry: Comparisons of Thrombolysis and Primary PCI Stenestrad U, et al. JAMA. 2006;296:1749-1756. 2.0 0.79 (0.70–0.88) 3.4 0.88 (0.68–1.14) 4.0 1.00 In-hospital reinfarction (%) Adjusted HR (95% CI) 4 0.68 (0.65–0.70) 5 0.83 (0.80–0.87) 6 1.00 Hospital stay for index event (days) Adjusted HR (95% CI) 4.8 0.61 (0.53–0.71) 9.0 1.02 (0.90–1.17) 9.6 1.00 Readmission for MI in 1st year (%) Adjusted HR (95% CI) 7.6 0.66 (0.60–0.76) 10.3 0.84 (0.74–0.95) 15.9 1.00 Mortality at 1 year (%) Adjusted HR (95% CI) 4.9 0.61 (0.53–0.71) 7.6 0.87 (0.76–1.01) 11.4 1.00 Mortality at 30 days (%) Adjusted HR (95% CI) 3.5 0.61 (0.51–0.73) 5.9 0.90 (0.76–1.06) 8.8 1.00 Mortality at 7 days (%) Adjusted HR (95% CI) Primary PCI, n=7084 Prehospital thrombolysis, n=3078 In-hospital thrombolysis, n=16,043 End point

16. RIKS-HIA Registry: Time to Reperfusion: 30-Day and 1-Year Mortality Stenestrad U, et al. JAMA. 2006;296:1749-1756. 4.5 8.9 11.4 Time to reperfusion >2 h 1-year mortality (%) 6.7 8.0 11.9 Time to reperfusion <2 h 7.3 11.8 16.3 Time to reperfusion >2 h 3.8 5.6 8.6 Time to reperfusion <2 h 30-day mortality (%) Primary PCI Prehospital thrombolysis In-hospital thrombolysis End point

17. Estimated Cumulative Mortality for Patients Receiving Reperfusion Treatment Within ≤2 or >2 Hours of Symptom Onset 8892 7675 7519 7417 1155 1020 1004 997 3592 3375 3344 3318 No. at Risk Thrombolysis Prehospital 3993 3571 3530 3490 Posthospital 1155 1077 1066 1060 Primary PCI 979 936 928 916 Mortality curves calculated using Cox regression analysis including propensity score for primary PCI. Reprinted with permission from Stenestrad U, et al. JAMA. 2006;296:1749-1756. 20 15 10 5 0 100 200 300 400 Cumulative Mortality, % Days Reperfusion >2 h In-Hospital Thrombolysis Prehospital Thrombolysis Primary Percutaneous Coronary Intervention (PCI) 20 15 10 5 0 100 200 300 400 Cumulative Mortality, % Days Reperfusion ≤2 h

19. Pooled Analysis: Primary PCI vs In-Hospital Fibrinolysis Reproduced with permission from Boersma E, et al. Eur Heart J. 2006;27:779-788. 30-day death in patients randomized to primary PCI compared with fibrinolysis according to presentation delay (left panel) and PCI-related delay (right panel) Primary PCI was associated with significantly lower 30-day mortality relative to fibrinolysis, regardless of treatment delay Presentation Number of 30-day delay (h) patients death (%) FL PPCI 0-1 747 6.0 4.7 >1-2 2000 6.2 4.2 >2-3 1712 7.3 5.1 >3-6 1640 9.5 5.6 >6-12 664 12.7 8.5 All patients 6763 7.9 5.3 PCI-related Number of 30-day delay (min) patients death (%) FL PPCI 0-35 1417 8.2 2.8 >35-50 1292 6.8 5.4 >50-62 1425 5.4 4.8 >62-79 1280 9.5 6.9 >79-120 1349 9.6 6.6 All patients 6763 7.9 5.3 0.63 (0.42, 0.84) OR and 95% Cl 0.0 0.5 1.0 1.5 PPCI better FL better 0.0 0.5 1.0 1.5 PPCI better FL better OR and 95% Cl

21. OAT: Baseline Characteristics of the Study Population * P =.02. Hochman JS, et al. N Engl J Med. 2006. November 14. [Epub ahead of print]. 252/1084 (23) 117/1084 (11) 32/1084 (3) 39/1082 (4) 24/1082 (2) 53/1084 (5) 4/1084 (0.4) 246/1084 (23)* 236/1081 (22) 127/1082 (12) 46/1081 (4) 42/1081 (4) 26/1081 (2) 51/1081 (5) 5/1082 (0.5) 200/1082 (18) History, no/total no (%) Angina MI Cerebrovascular disease Peripheral-vessel disease Heart failure PCI CABG Diabetes 845 (78) 239 (22) 845 (78) 237 (22) Sex, no. (%) Men Women 58.7 ±11.1 58.6 ± 10.8 Age, y Medical Therapy Group (n=1084) PCI Group (n=1082) Characteristic

22. OAT: Baseline Characteristics of the Study Population *Investigators at the study site reported the ejection fraction if a left ventriculogram was not obtained. Hochman JS, et al. N Engl J Med. 2006. November 14. [Epub ahead of print]. 48.0 ±11.0 554/1075 (52) 206/1075 (19) 47.4 ±11.3 597/1075 (56) 236/1075 (22) Ejection Fraction* Mean <50%, no/total no(%) <40%, no/total no (%) 191/1075 (18) 192/1074 (18) Multivessel disease, no/ total no (%) 932/1084 (86) 939/1082 (87) ST-segment elevation or Q-wave or R-wave loss 681/1039 (66) 700/1037 (68) ST-segment elevation 427/1084 (39) 423/1082 (39) Current cigarette smoker, no/total no (%) Medical Therapy Group (n=1084) PCI Group (n=1082) Characteristic

23. OAT: Estimated 4-Year Cumulative Event Rates Hochman JS, et al. N Engl J Med. 2006. November 14. [Epub ahead of print]. .83 0.77–1.40 1.03 9.4 9.1 Death .92 0.64–1.49 0.98 4.5 4.4 NYHA class 4 HF .08 0.96–2.16 1.44 5.0 6.9 Nonfatal MI .13 0.92–2.00 1.36 5.3 7.0 All MI .20 0.92–1.45 1.16 15.6 17.2 Death, MI, HF P 95% CI HR Medical (%) PCI (%) Outcome

25. CHICAGO: Progression of Mean and Maximum CIMT at Week 72 Mazzone T, et al . JAMA . 2006. November 13. [Epub ahead of print]. – 0.013 (–0.024 to 0.002) Difference (95% CI) .02 +0.012 – 0.001 Primary end point, mm P Glimepiride Pioglitazone Mean CIMT: End Point – 0.024 (–0.042 to 0.006) Difference (95% CI) .008 +0.026 +0.002 Progression of maximum CIMT, mm P Glimepiride Pioglitazone Maximum CIMT: End Point

26. APEX-AMI: Outcomes at 30 Days (Revised End Points and Time Frame) Armstrong PW. Presented at: American Heart Association 2006 Scientific Sessions; November 14, 2006. *Primary end point, revised from 90-day all-cause mortality in original protocol. No significant differences. 9.19 8.99 Death, shock, or HF 3.92 4.06 All-cause mortality* Placebo, n=2885 (%) Pexelizumab, n=2860 (%) End point

27. *Original primary end point, later revised to 30-day all-cause mortality. No significant differences. Armstrong PW. Presented at: American Heart Association 2006 Scientific Sessions; November 14, 2006. APEX-AMI: Outcomes at 90 Days 1.36 1.18 Stroke 3.04 2.39 Reinfarction 3.36 3.47 Cardiogenic shock 4.76 4.82 Incident heart failure 4.93 4.51 All-cause mortality* Placebo, n=2885 (%) Pexelizumab, n=2860 (%) End point

28. Featured Institution University of California, Davis Medical Center Sacramento, California

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

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

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

33. Question-and-Answer Session

34. Concluding Remarks Gregg C. Fonarow, MD Next Program Christopher P. Cannon, MD Wednesday, January 17, 2007 12:00 Noon Eastern Time (9:00 AM Pacific Time)