1. Impact of Drug-Eluting Stents on Revascularization Choices in Patients with Acute Coronary Syndromes and Multivessel Coronary Disease: Results from the CRUSADE Quality Improvement Initiative Gogo PB, Dauerman HL, Mulgund J, Ohman EM, Gibler WB, Patel MR, Harrington RA, Peterson ED, and Roe MT for the CRUSADE investigators

2. AcknowledgementAcknowledgement n CRUSADE is a National Quality Improvement Initiative of the Duke Clinical Research Institute. CRUSADE is funded by Schering Corporation. The Bristol-Myers Squibb/Sanofi-Aventis Pharmaceuticals Partnership provides additional funding support. Millennium Pharmaceuticals also provided funding for this study.

3. DisclosuresDisclosures PB Gogo 1, HL Dauerman 1, J Mulgund 1, MR Patel 1, EM Ohman 2, WB Gibler 2, RA Harrington 2, ED Peterson 2, MT Roe 2,3 1 None 2 Millennium Pharmaceuticals, Inc.; Bristol-Myers Squibb/Sanofi- Aventis Pharmaceuticals Partnership; Schering Corporation; Significant, Research Grants 3 Millennium Pharmaceuticals, Inc.; Bristol-Myers Squibb/Sanofi- Aventis Pharmaceuticals Partnership; Schering Corporation; Significant, Speakers Bureau

4. BackgroundBackground n CRUSADE is a national quality improvement initiative involving > 500 U.S. hospitals; it is designed to improve the care of high-risk patients with non–ST-segment elevation acute coronary syndromes. n Approximately 80% of U.S. patients receive DES during PCI. n Recent registry data (ARTS II) suggests that PCI with DES may be a reasonable alternative to CABG surgery for patients with multivessel CAD n CRUSADE is a national quality improvement initiative involving > 500 U.S. hospitals; it is designed to improve the care of high-risk patients with non–ST-segment elevation acute coronary syndromes. n Approximately 80% of U.S. patients receive DES during PCI. n Recent registry data (ARTS II) suggests that PCI with DES may be a reasonable alternative to CABG surgery for patients with multivessel CAD

5. Study Objectives n To characterize temporal trends in the use of PCI vs. CABG vs. medical therapy in all NSTE acute coronary syndrome patients since the introduction of DES n To characterize temporal trends in the use of PCI vs. CABG vs. medical therapy for NSTE ACS patients with 3-vessel CAD since the introduction of DES n To characterize temporal trends in the use of PCI vs. CABG vs. medical therapy in all NSTE acute coronary syndrome patients since the introduction of DES n To characterize temporal trends in the use of PCI vs. CABG vs. medical therapy for NSTE ACS patients with 3-vessel CAD since the introduction of DES

6. Inclusion Criteria for CRUSADE n Ischemic symptoms lasting  10 minutes within 24 hours and at least one of the following: n Positive cardiac markers l CK-MB or TnI / TnT above ULN l Positive bedside troponin assay n Dynamic ST-segment ECG changes: l ST-segment depression  0.5 mm l Transient ST-segment elevation  1 mm (lasting < 30 mins) n Ischemic symptoms lasting  10 minutes within 24 hours and at least one of the following: n Positive cardiac markers l CK-MB or TnI / TnT above ULN l Positive bedside troponin assay n Dynamic ST-segment ECG changes: l ST-segment depression  0.5 mm l Transient ST-segment elevation  1 mm (lasting < 30 mins)

7. Analysis Population n = 148,147 n = 103,288 n = 25,068 All patients in CRUSADE Initiative From Jan. 2002 to June 2005 Patients were excluded at hospitals without both PCI/CABG capability as well as if they had contraindications to catheterization  Overall revascularization analysis Subgroup of patients with three vessel CAD  3-vessel CAD revascularization analysis

8. Data Collection and Data Analysis n Sites participate in a retrospective chart review for in-hospital medications, procedures, and outcomes. n Temporal trends for the use of revascularization versus medical therapy in all patients were measured. n Factors associated with use of PCI vs. CABG for patients with 3-vessel CAD were determined by logistic regression analysis. n Sites participate in a retrospective chart review for in-hospital medications, procedures, and outcomes. n Temporal trends for the use of revascularization versus medical therapy in all patients were measured. n Factors associated with use of PCI vs. CABG for patients with 3-vessel CAD were determined by logistic regression analysis.

9. Results for All Patients: 103,288 Patients with High Risk NSTE Acute Coronary Syndromes

10. Temporal Trends in the Use of Revascularization Among All Patients PeriodCABG SurgeryPCIMedical Therapy Jan-Mar 200212.8%38.3%48.9% Apr-Jun 200213.1%39.8%47.0% Jul-Sep 200213.6%40.2%46.2% Oct-Dec 200214.3%40.0%45.7% Jan-Mar 200312.8%39.7%47.5% Apr-Jun 200312.2%39.9%48.0% Jul-Sep 200312.5%41.1%46.3% Oct-Dec 200313.9%50.2%35.9% Jan-Mar 200414.8%50.8%34.5% Apr-Jun 200414.0%53.2%32.8% Jul-Sep 200413.1%52.6%34.3% Oct-Dec 200413.4%53.3%33.2% Jan-Mar 200513.3%53.2%33.5% Apr-Jun 200511.9%52.5%35.5% Drug-eluting stents Approved by FDA p for trend in CABG surgery is not significant

11. Temporal Trends in Type of Revascularization Strategy in All Patients: PCI vs. CABG p for trend <0.01 PeriodCABG SurgeryPCI Jan-Mar 200225.1%74.9% Apr-Jun 200224.9%75.1% Jul-Sep 200225.3%74.7% Oct-Dec 200226.3%73.7% Jan-Mar 200324.4%75.6% Apr-Jun 200323.4%76.6% Jul-Sep 200323.4%76.6% Oct-Dec 200321.7%78.3% Jan-Mar 200422.5%77.5% Apr-Jun 200420.8%79.2% Jul-Sep 200419.9%80.1% Oct-Dec 200420.2%79.8% Jan-Mar 200520.0%80.0% Apr-Jun 200518.5%81.5% Drug-eluting stents Approved by FDA

12. A Significant Reduction in the Use of Medical Therapy Alone Among All Patients

13. Sub-Group Analysis (N=25,068): Patients with 3-Vessel Coronary Artery Disease

14. Use of Drug-Eluting Stents in CRUSADE * Kandzari, AJC, 2005. *

15. Baseline Characteristics of Patients Over Time: 3-Vessel Coronary Artery Disease Overall n=25,036 Before DES n=8583 After DES n=16,485 P Age, y, median67.2 0.99 Female30.5%31.4%30.1%0.05 White83.7%83.6%83.8%0.07 Diabetes mellitus38.4%38.9%38.1%0.42 Renal insufficiency12.1%12.0%12.2%0.61 Hypertension73.3%72.9%73.5%0.35 Dyslipidemia57.9%56.0%58.9%<0.01 Smoking27.8% 27.9%0.99 Prior CABG30.4%30.1%30.6%0.61 Prior PCI24.0%24.4%23.7%0.12 Prior Stroke9.9%9.7%9.9%0.71 Prior MI33.7%35.3%32.8%<0.01 Prior CHF14.3%14.8%14.1%0.10

16. Clinical Presentation of Patients Over Time: 3-Vessel Coronary Artery Disease Before DES n=8583After DES n=16,485P CHF at presentation21.7%22.2%0.53 Positive cardiac markers89.9%92.2%<0.01 ST depression41.7%37.5%<0.01 Transient ST elevation7.0%6.1%<0.01

17. Temporal Trends in Revascularization and Medical Therapy Among Patients with 3-Vessel CAD PeriodCABG SurgeryPCIMedical Therapy Jan-Mar 200235.2%36.9%27.9% Apr-Jun 200239.0%36.2%24.7% Jul-Sep 200238.8%34.6%26.7% Oct-Dec 200239.6%34.0%26.4% Jan-Mar 200334.8%37.2%28.0% Apr-Jun 200336.1%34.4%29.6% Jul-Sep 200336.7%38.0%25.3% Oct-Dec 200334.7%40.7%24.6% Jan-Mar 200436.5%36.7%25.8% Apr-Jun 200435.2%39.0%25.8% Jul-Sep 200431.9%41.2%26.9% Oct-Dec 200433.1%40.9%26.0% Jan-Mar 200532.2%42.4%25.4% Apr-Jun 200529.7%44.8%25.5% Drug-eluting stents Approved by FDA p for trend in CABG surgery <0.01

18. The Use of Medical Therapy Alone in Patients With 3-Vessel CAD was Constant Over Time

19. Trends in Type of Revascularization Strategy for 3-Vessel CAD: PCI vs. CABG

20. Factors Associated with Use of PCI vs. CABG for 3-Vessel CAD (n=18,462) Changed after DES IntroductionAdjusted OR95% CI Prior CABG surgery, before DES7.966.81-9.30 Prior CABG surgery, after DES9.758.42-11.30 Unchanged after DES Introduction Previous PCI1.611.50-1.74 Male0.730.68-0.78 ST-depression (vs. none)0.790.74-0.85 Transient ST-elevation (vs. none)1.201.06-1.35 Cardiology Inpatient Care1.421.23-1.65 Academic Hospital1.361.14-1.62 Renal Insufficiency1.211.08-1.36 Previous history of CHF1.211.08-1.35 Family history of CAD0.890.83-0.95 Hypertension0.900.84-0.97 CHF at presentation0.880.80-0.96

21. Limitations n The reasons for use of revascularization strategies or medical therapy alone were not prospectively collected by sites. n Detailed angiographic characteristics were not collected; the influence of lesion type and severity on revascularization decisions could not be determined. n Long-term outcomes (including rates of stent thrombosis, death, and repeat revascularization) were not collected. n The reasons for use of revascularization strategies or medical therapy alone were not prospectively collected by sites. n Detailed angiographic characteristics were not collected; the influence of lesion type and severity on revascularization decisions could not be determined. n Long-term outcomes (including rates of stent thrombosis, death, and repeat revascularization) were not collected.

22. Conclusions (1) n The introduction of drug eluting stents has been associated with increased use of revascularization in all patients with NSTE ACS. n Among patients with 3-vessel coronary artery disease, PCI is now the predominant mode of revascularization. n The introduction of drug eluting stents has been associated with increased use of revascularization in all patients with NSTE ACS. n Among patients with 3-vessel coronary artery disease, PCI is now the predominant mode of revascularization.

23. Conclusions (2) n One-fourth of patients with 3-vessel coronary artery disease are still managed medically in current practice, and this proportion has not changed due to DES introduction. n Randomized trials are needed to determine the impact of PCI vs. CABG for patients with 3-vessel CAD. n One-fourth of patients with 3-vessel coronary artery disease are still managed medically in current practice, and this proportion has not changed due to DES introduction. n Randomized trials are needed to determine the impact of PCI vs. CABG for patients with 3-vessel CAD.