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

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.

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

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

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

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)

Analysis Population n = 148,147 n = 103,288 n = 25,068 All patients in CRUSADE Initiative From Jan 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

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.

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

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

Temporal Trends in Type of Revascularization Strategy in All Patients: PCI vs. CABG p for trend <0.01 PeriodCABG SurgeryPCI Jan-Mar %74.9% Apr-Jun %75.1% Jul-Sep %74.7% Oct-Dec %73.7% Jan-Mar %75.6% Apr-Jun %76.6% Jul-Sep %76.6% Oct-Dec %78.3% Jan-Mar %77.5% Apr-Jun %79.2% Jul-Sep %80.1% Oct-Dec %79.8% Jan-Mar %80.0% Apr-Jun %81.5% Drug-eluting stents Approved by FDA

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

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

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

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, median 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

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

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

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

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

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 DES Prior CABG surgery, after DES Unchanged after DES Introduction Previous PCI Male ST-depression (vs. none) Transient ST-elevation (vs. none) Cardiology Inpatient Care Academic Hospital Renal Insufficiency Previous history of CHF Family history of CAD Hypertension CHF at presentation

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.

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.

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.