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

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 Gogo PB, Dauerman HL, Mulgund J, Ohman EM, Gibler WB, Patel MR, Harrington RA, Peterson ED, and Roe WB, Patel MR, Harrington RA, Peterson ED, and Roe

MT MT for the CRUSADE investigatorsfor the CRUSADE investigators

AcknowledgementAcknowledgementAcknowledgementAcknowledgement

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.

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.

DisclosuresDisclosuresDisclosuresDisclosures

PB GogoPB Gogo11, HL Dauerman, HL Dauerman11, J Mulgund, J Mulgund11, MR Patel, MR Patel11, EM Ohman, EM Ohman22, , WB GiblerWB Gibler22, RA Harrington, RA Harrington22, ED Peterson, ED Peterson22, MT Roe, MT Roe2,32,3

1 None 1 None 2 Millennium Pharmaceuticals, Inc.; Bristol-Myers Squibb/Sanofi-2 Millennium Pharmaceuticals, Inc.; Bristol-Myers Squibb/Sanofi-

Aventis Pharmaceuticals Partnership; Schering Corporation; Aventis Pharmaceuticals Partnership; Schering Corporation; Significant, Research GrantsSignificant, Research Grants

3 Millennium Pharmaceuticals, Inc.; Bristol-Myers Squibb/Sanofi-3 Millennium Pharmaceuticals, Inc.; Bristol-Myers Squibb/Sanofi-Aventis Pharmaceuticals Partnership; Schering Corporation; Aventis Pharmaceuticals Partnership; Schering Corporation; Significant, Speakers BureauSignificant, Speakers Bureau

BackgroundBackgroundBackgroundBackground 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.

Approximately 80% of U.S. patients receive DES during PCI.

Recent registry data (ARTS II) suggests that PCI with DES may be a reasonable alternative to CABG surgery for patients with multivessel CAD

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.

Approximately 80% of U.S. patients receive DES during PCI.

Recent registry data (ARTS II) suggests that PCI with DES may be a reasonable alternative to CABG surgery for patients with multivessel CAD

Study ObjectivesStudy Objectives

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

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

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

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 CRUSADEInclusion Criteria for CRUSADE

Ischemic symptoms lasting Ischemic symptoms lasting 10 minutes within 10 minutes within 24 hours and at least 24 hours and at least oneone of the following: of the following:

Positive cardiac markersPositive cardiac markers CK-MB or TnI / TnT above ULNCK-MB or TnI / TnT above ULN Positive bedside troponin assayPositive bedside troponin assay

Dynamic ST-segment ECG changes:Dynamic ST-segment ECG changes: ST-segment depression ST-segment depression 0.5 mm 0.5 mm Transient ST-segment elevation Transient ST-segment elevation 1 mm (lasting 1 mm (lasting

< 30 mins)< 30 mins)

Ischemic symptoms lasting Ischemic symptoms lasting 10 minutes within 10 minutes within 24 hours and at least 24 hours and at least oneone of the following: of the following:

Positive cardiac markersPositive cardiac markers CK-MB or TnI / TnT above ULNCK-MB or TnI / TnT above ULN Positive bedside troponin assayPositive bedside troponin assay

Dynamic ST-segment ECG changes:Dynamic ST-segment ECG changes: ST-segment depression ST-segment depression 0.5 mm 0.5 mm Transient ST-segment elevation Transient ST-segment elevation 1 mm (lasting 1 mm (lasting

< 30 mins)< 30 mins)

Analysis PopulationAnalysis Population

n = 148,147

n = 103,288

n = 25,068

All patients in CRUSADE Initiative All patients in CRUSADE Initiative From Jan. 2002 to June 2005From Jan. 2002 to June 2005

Patients were excluded at hospitals Patients were excluded at hospitals without both PCI/CABG capability as well without both PCI/CABG capability as well as if they had contraindications to as if they had contraindications to catheterizationcatheterization Overall revascularization analysis Overall revascularization analysis

Subgroup of patients with three vessel CADSubgroup of patients with three vessel CAD 3-vessel CAD revascularization analysis 3-vessel CAD revascularization analysis

Data Collection and Data AnalysisData Collection and Data Analysis

Sites participate in a retrospective chart review for in-hospital medications, procedures, and outcomes.

Temporal trends for the use of revascularization versus medical therapy in all patients were measured.

Factors associated with use of PCI vs. CABG for patients with 3-vessel CAD were determined by logistic regression analysis.

Sites participate in a retrospective chart review for in-hospital medications, procedures, and outcomes.

Temporal trends for the use of revascularization versus medical therapy in all patients were measured.

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

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

Acute Coronary Syndromes

Temporal Trends in the Use of Revascularization Among All Patients

Temporal Trends in the Use of Revascularization Among All Patients

PeriodPeriod CABG Surgery PCI Medical Therapy

Jan-Mar 2002 12.8% 38.3% 48.9%

Apr-Jun 2002 13.1% 39.8% 47.0%

Jul-Sep 2002 13.6% 40.2% 46.2%

Oct-Dec 2002 14.3% 40.0% 45.7%

Jan-Mar 2003 12.8% 39.7% 47.5%

Apr-Jun 2003 12.2% 39.9% 48.0%

Jul-Sep 2003 12.5% 41.1% 46.3%

Oct-Dec 2003 13.9% 50.2% 35.9%

Jan-Mar 2004 14.8% 50.8% 34.5%

Apr-Jun 2004 14.0% 53.2% 32.8%

Jul-Sep 2004 13.1% 52.6% 34.3%

Oct-Dec 2004 13.4% 53.3% 33.2%

Jan-Mar 2005 13.3% 53.2% 33.5%

Apr-Jun 2005 11.9% 52.5% 35.5%

Drug-eluting stentsApproved by FDA

p for trend in CABGp for trend in CABGsurgery is not surgery is not significantsignificant

Temporal Trends in Type of Revascularization Strategy in All Patients: PCI vs. CABG

Temporal Trends in Type of Revascularization Strategy in All Patients: PCI vs. CABG

p for trend p for trend <0.01<0.01

PeriodPeriod CABG Surgery PCI

Jan-Mar 2002 25.1% 74.9%

Apr-Jun 2002 24.9% 75.1%

Jul-Sep 2002 25.3% 74.7%

Oct-Dec 2002 26.3% 73.7%

Jan-Mar 2003 24.4% 75.6%

Apr-Jun 2003 23.4% 76.6%

Jul-Sep 2003 23.4% 76.6%

Oct-Dec 2003 21.7% 78.3%

Jan-Mar 2004 22.5% 77.5%

Apr-Jun 2004 20.8% 79.2%

Jul-Sep 2004 19.9% 80.1%

Oct-Dec 2004 20.2% 79.8%

Jan-Mar 2005 20.0% 80.0%

Apr-Jun 2005 18.5% 81.5%

Drug-eluting stentsApproved by FDA

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

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

30

35

40

45

50

55

60

Med

ical T

hera

py, %

FDA approves DES

p<0.01

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

Coronary Artery Disease

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

Coronary Artery Disease

Use of Drug-Eluting Stents in CRUSADEUse of Drug-Eluting Stents in CRUSADE

30

40

50

60

70

80

90

100

Q4 2003 Q1 2004 Q2 2004 Q3 2004 Q4 2004 Q1 2005 Q2 2005

DE

S U

se,

%

All Patients 3VD

30

40

50

60

70

80

90

100

Q4 2003 Q1 2004 Q2 2004 Q3 2004 Q4 2004 Q1 2005 Q2 2005

DE

S U

se,

%

All Patients 3VD

* Kandzari, AJC, 2005.

*

Baseline Characteristics of Patients Over Time:3-Vessel Coronary Artery Disease

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 67.2 67.2 67.2 0.99

Female 30.5% 31.4% 30.1% 0.05

White 83.7% 83.6% 83.8% 0.07

Diabetes mellitus 38.4% 38.9% 38.1% 0.42

Renal insufficiency 12.1% 12.0% 12.2% 0.61

Hypertension 73.3% 72.9% 73.5% 0.35

Dyslipidemia 57.9% 56.0% 58.9% <0.01

Smoking 27.8% 27.8% 27.9% 0.99

Prior CABG 30.4% 30.1% 30.6% 0.61

Prior PCI 24.0% 24.4% 23.7% 0.12

Prior Stroke 9.9% 9.7% 9.9% 0.71

Prior MI 33.7% 35.3% 32.8% <0.01

Prior CHF 14.3% 14.8% 14.1% 0.10

Clinical Presentation of Patients Over Time: 3-Vessel Coronary Artery Disease

Clinical Presentation of Patients Over Time: 3-Vessel Coronary Artery Disease

Before DES n=8583 After DES n=16,485 P

CHF at presentation 21.7% 22.2% 0.53

Positive cardiac markers 89.9% 92.2% <0.01

ST depression 41.7% 37.5% <0.01

Transient ST elevation 7.0% 6.1% <0.01

Temporal Trends in Revascularization and Medical Therapy Among Patients with 3-Vessel CAD

Temporal Trends in Revascularization and Medical Therapy Among Patients with 3-Vessel CAD

PeriodPeriod CABG Surgery PCI Medical Therapy

Jan-Mar 2002 35.2% 36.9% 27.9%

Apr-Jun 2002 39.0% 36.2% 24.7%

Jul-Sep 2002 38.8% 34.6% 26.7%

Oct-Dec 2002 39.6% 34.0% 26.4%

Jan-Mar 2003 34.8% 37.2% 28.0%

Apr-Jun 2003 36.1% 34.4% 29.6%

Jul-Sep 2003 36.7% 38.0% 25.3%

Oct-Dec 2003 34.7% 40.7% 24.6%

Jan-Mar 2004 36.5% 36.7% 25.8%

Apr-Jun 2004 35.2% 39.0% 25.8%

Jul-Sep 2004 31.9% 41.2% 26.9%

Oct-Dec 2004 33.1% 40.9% 26.0%

Jan-Mar 2005 32.2% 42.4% 25.4%

Apr-Jun 2005 29.7% 44.8% 25.5%

Drug-eluting stentsApproved by FDA

p for trend in CABGp for trend in CABGsurgery <0.01surgery <0.01

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

Over Time

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

Over Time

0

10

20

30

40

50

Perc

en

t

FDA approves DES

p=NS

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

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

35

40

45

50

55

60

65

Percent

CABG PCI

FDA approves DES

p<0.01 for trend in CABG rates

35

40

45

50

55

60

65

Percent

CABG PCI

FDA approves DES

p<0.01 for trend in CABG rates

Factors Associated with Use of PCI vs. CABG for 3-Vessel CAD (n=18,462)

Factors Associated with Use of PCI vs. CABG for 3-Vessel CAD (n=18,462)

Changed after DES Introduction Adjusted OR 95% CI

Prior CABG surgery, before DES 7.96 6.81-9.30

Prior CABG surgery, after DES 9.75 8.42-11.30

Unchanged after DES Introduction

Previous PCI 1.61 1.50-1.74

Male 0.73 0.68-0.78

ST-depression (vs. none) 0.79 0.74-0.85

Transient ST-elevation (vs. none) 1.20 1.06-1.35

Cardiology Inpatient Care 1.42 1.23-1.65

Academic Hospital 1.36 1.14-1.62

Renal Insufficiency 1.21 1.08-1.36

Previous history of CHF 1.21 1.08-1.35

Family history of CAD 0.89 0.83-0.95

Hypertension 0.90 0.84-0.97

CHF at presentation 0.88 0.80-0.96

LimitationsLimitations

The reasons for use of revascularization strategies or medical therapy alone were not prospectively collected by sites.

Detailed angiographic characteristics were not collected; the influence of lesion type and severity on revascularization decisions could not be determined.

Long-term outcomes (including rates of stent thrombosis, death, and repeat revascularization) were not collected.

The reasons for use of revascularization strategies or medical therapy alone were not prospectively collected by sites.

Detailed angiographic characteristics were not collected; the influence of lesion type and severity on revascularization decisions could not be determined.

Long-term outcomes (including rates of stent thrombosis, death, and repeat revascularization) were not collected.

Conclusions (1)Conclusions (1)

The introduction of drug eluting stents has been associated with increased use of revascularization in all patients with NSTE ACS.

Among patients with 3-vessel coronary artery disease, PCI is now the predominant mode of revascularization.

The introduction of drug eluting stents has been associated with increased use of revascularization in all patients with NSTE ACS.

Among patients with 3-vessel coronary artery disease, PCI is now the predominant mode of revascularization.

Conclusions (2)Conclusions (2)

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.

Randomized trials are needed to determine the impact of PCI vs. CABG for patients with 3-vessel CAD.

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.

Randomized trials are needed to determine the impact of PCI vs. CABG for patients with 3-vessel CAD.