Unrestricted Use of Drug-Eluting Stents Unrestricted Use of Drug-Eluting Stents Compared with Bare-Metal Stents in Compared with Bare-Metal Stents in

Routine Clinical Practice: Findings From Routine Clinical Practice: Findings From the National Heart, Lung, and Blood the National Heart, Lung, and Blood

Institute Dynamic RegistryInstitute Dynamic Registry

Unrestricted Use of Drug-Eluting Stents Unrestricted Use of Drug-Eluting Stents Compared with Bare-Metal Stents in Compared with Bare-Metal Stents in

Routine Clinical Practice: Findings From Routine Clinical Practice: Findings From the National Heart, Lung, and Blood the National Heart, Lung, and Blood

Institute Dynamic RegistryInstitute Dynamic Registry

J. Dawn Abbott, MD, FACC,* Matthew R. Voss, MD,* Mamoo Nakamura, MD,† Howard A. Cohen, MD, FACC,‡ Faith Selzer, PHD,† Kevin E. Kip, PHD, Helen A. Vlachos, MSC,†Robert L.

Wilensky, MD, FACC,§ David O. Williams, MD, FACC*

Providence, Rhode Island; Pittsburgh and Philadelphia, Pennsylvania; and New York, New York

Abbott, J. D. et al. J Am Coll Cardiol 2007;50:2029-36

Drug-eluting vs. Bare Metal Drug-eluting vs. Bare Metal Stents: BackgroundStents: BackgroundDrug-eluting vs. Bare Metal Drug-eluting vs. Bare Metal Stents: BackgroundStents: Background Stents are utilized almost uniformly in patients

undergoing percutaneous coronary intervention Until recently, drug-eluting stents have been the

preferred treatment Some have raised concerns that drug-eluting stents may

be associated with more frequent stent thrombosis leading to excess death and MI

Robust comparisons of drug-eluting and bare metal stents have been limited to highly selected, simple patient subgroups.

Comparisons between DES and BMS for non-protocol usage in North America have been limited

Drug-eluting vs. Bare Metal Drug-eluting vs. Bare Metal Stents: Purpose of InvestigationStents: Purpose of InvestigationDrug-eluting vs. Bare Metal Drug-eluting vs. Bare Metal Stents: Purpose of InvestigationStents: Purpose of Investigation

In the setting of routine clinical practice to: Determine and compare the baseline clinical and

angiographic features, procedural strategies and clinical outcomes of patients treated with a bare metal and drug-eluting stent

Compare outcomes following adjustments for baseline imbalances

Dynamic RegistryDynamic RegistryDynamic RegistryDynamic Registry Prospective observational multicenter study Enrollment of sequential “waves” of consecutive

patients having coronary intervention Exclusion: Refusal or inability to provide written

informed consent 2000 patients per wave separated by 18 months Trained research coordinators collect data Oversampling of women and minorities Follow-up obtained by phone at 30 days, 6 months, 1

year Funding just received to follow patients for five years

Study DesignStudy Design

Identified patients treated with DES in Wave 4 (2004) and compared them to patients treated with a BMS in Wave 3 (2002)

Wave 3 represented the last wave before the routine availability of DES

Intent of excluding wave 4 BMS patients was to eliminate selection bias seen in Wave 4

Patients treated with BMS in Wave 3 would likely have been treated with DES had one been available

One-year follow-up data was available in 93% of wave 3 patients and 96% of wave 4 patients

DES vs. BMS: Study PopulationDES vs. BMS: Study PopulationBMS Era

October 2001 to March 2002N=2047

DES EraFebruary to May 2004

N=2112

Exclude if no stentN=284

Exclude if only BMS or no stentN=652

BMS GroupN=1763

2551 lesions

DES GroupN=1460

1995 lesionsSES 59.8%PES 31.5%

Statistical AnalysisStatistical Analysis Univariate differences between BMS and DES

Categorical variables: chi-square test Continuous data: Wilcoxon rank-sum test

Cumulative one-year event rates Kaplan-Meier approach and compared by log-rank

statistic Multivariable analysis

Cox proportional hazards regression used to estimate unadjusted and adjusted hazard ratios of adverse clinical outcomes

Probability values <0.05 were considered significant

Variable BMS

n=1763

DES

n=1460

p-value

Mean Age (years) 64.4 63.7 0.07

% Female 35.8 33.3 0.14

Diabetes, % 29.1 34.3 0.001

Hypertension, % 74.1 79.1 0.001

Hypercholesterolemia, %69.8 77.5

<0.0001

Current smoking, % 24.4 21.4 0.05

Prior myocardial infarction, % 26.2 26.4 0.90

Prior coronary bypass, % 17.4 19.1 0.21

Prior angioplasty, % 27.3 32.4 0.002

Renal insufficiency 7.1 9.1 0.03

DES vs. BMS:Baseline Characteristics

Variable BMS

n=1763

DES

n=1460

p-value

Vessel Disease 0.098

Single 37.6 33.8

Double 32.0 32.5

Triple 30.1 33.5

Indication for procedure, %

<0.0001

Acute MI 29.8 23.8

Unstable Angina 39.9 35.9

Stable Angina 19.7 25

Other 10.6 15.3

Ejection Fraction, mean 51.5 52.3 0.09

Cardiogenic Shock 2.1 0.5 <0.0001

DES vs. BMS:Baseline Characteristics

Variable BMS

n=2551

DES

n=1995

p-value

Mean Reference Vessel Diameter

3.1 3.0 0.07

Mean Lesion Length 13.4 15.9 <0.0001

Lesion Types, %

Total Occlusion 9.2 7.4 0.03

Thrombus 15.4 11.0 <0.0001

Calcified 22.3 26.5 0.001

Bifurcation 13.2 10.2 0.002

Ostial 6.9 8.8 0.02

Lesion Tortuosity, %

None/Mild 75.0 73.2 0.19

Moderate/Severe Tortuosity 25 26.8

DES vs. BMS:Attempted Lesion Characteristics

DES vs. BMS: DES vs. BMS: Procedural Characteristics

DES vs. BMS: DES vs. BMS: Procedural Characteristics

BMS

n= 2551

DES

n=1995

p-value

Lesion Complication, %

Abrupt Closure 0.2 0.0 0.03

Dissection 1.9 2.1 0.80

Side Branch Occlusion 2.1 2.2 0.85

Persistent flow reduction

0.7 0.9 0.68

Procedural Success, % 0.16

Complete 96.5 97.3

Partial 3.2 2.2

Failure 0.3 0.5

Angiographic success, % 97.5 98.0 0.33

Variable BMS

n=1763

DES

n=1460

p-value

Death 4.3 3.6 0.32

MI 4.7 4.6 0.93

CABG 3.1 1.2 <0.001

Target Vessel Revascularization

9.2 5.0 <0.001

Repeat PCI 12.7 9.0 0.001

MACE

(Death, MI, Repeat Revascularization)

20.9 15.5 <0.001

DES vs. BMS: DES vs. BMS: Cumulative Unadjusted One-Year Event Rates

Stent ThrombosisStent Thrombosis

Definite stent thrombosis reported Over 1 year 1.0% of DES patients (n=14)

0.8% (n=11) subacute 0.2% (n=3) late

Data were not collected during wave 3 not available for BMS patients

DES vs. BMS: Adjusted and Unadjusted Events at One-Year

DES vs. BMS: Adjusted and Unadjusted Events at One-Year

Adverse Outcome

HR

95% CI

p-value

Death Unadjusted Adjusted

0.83 0.97

0.57-1.20 0.66-1.43

0.32 0.87

Myocardial infarction (MI) Unadjusted Adjusted

0.99 1.02

0.71-1.37 0.73-1.43

0.93 0.90

Coronary artery bypass graft Unadjusted Adjusted

0.39 0.34

0.22-0.68 0.19-0.60

<0.001 <0.001

Death/MI Unadjusted Adjusted

0.88 0.88

0.68-1.13 0.68-1.15

0.31 0.34

Repeat angioplasty Unadjusted Adjusted

0.69 0.65

0.55-0.87 0.52-0.82

0.001

<0.001 Repeat revascularization Unadjusted Adjusted

0.64 0.38

0.52-0.79 0.25-0.60

<0.001 <0.001

MACE Unadjusted Adjusted

0.72 0.67

0.60-0.85 0.56-0.81

<0.001 <0.001

Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply.Abbott, J. D. et al. J Am Coll Cardiol 2007;50:2029-2036

Adjusted Kaplan-Meier Event Curves at 1 Year Freedom from (A) Death/MI (B) Repeat RevascularizationAdjusted Kaplan-Meier Event Curves at 1 Year Freedom from (A) Death/MI (B) Repeat Revascularization

One-year Event Rates for complex lesion types According to Stent TypeOne-year Event Rates for complex lesion types According to Stent Type

BMS DES p-value n Percent n Percent Death or MI Bifurcation + 261 9.3 189 6.4 0.32 Bifurcation - 1502 8.6 1271 7.8 0.44 Ostial + 163 12.1 168 11.4 0.92 Ostial - 1600 8.3 1292 7.1 0.22 Thrombus + 329 13.1 189 10.9 0.45 Thrombus - 1434 7.7 1262 7.1 0.59 Calcification + 424 9.7 407 9.2 0.89 Calcification - 1339 8.3 1053 6.9 0.20 Ulceration + 282 9.8 225 9.5 0.91 Ulceration - 1481 8.5 1235 7.2 0.26 TO + 212 12.1 143 12.9 0.93 TO - 1551 8.2 1371 7.0 0.27 Any present 1053 10.3 852 8.6 0.24 None present 710 6.3 608 6.2 0.93 TVR via PCI† Bifurcation + 225 8.6 182 7.2 0.67 Bifurcation - 1229 9.3 1230 4.6 <0.001 Ostial + 137 10.5 163 5.6 0.12 Ostial - 1317 9.1 1249 4.9 <0.001 Thrombus + 258 7.6 190 3.4 0.058 Thrombus - 1196 9.6 1222 5.2 <0.001 Calcification + 362 9.3 399 6.2 0.11 Calcification - 1092 9.2 1013 4.5 <0.001 Ulceration + 225 5.9 220 5.1 0.70 Ulceration - 1229 9.8 1192 4.9 <0.001 TO + 168 8.6 136 2.3 0.023 TO - 1286 9.3 1276 5.2 <0.001 Any 871 8.8 828 5.2 0.004 None 583 9.9 584 4.6 <0.001 * Rates calculated using Kaplan-Meier methodology.

Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply.Abbott, J. D. et al. J Am Coll Cardiol 2007;50:2029-2036

Adjusted HRs and 95% CIs for 1 Year (A) Death/MI (B) TVR

DES vs. BMS: ConclusionsDES vs. BMS: Conclusions DES as used in routine clinical practice in patients with

complex lesions resulted in a substantial reduction in clinically driven target vessel revascularization compared with BMS-treated patients

Overall risk of repeat revascularization after adjustment was 43% lower in DES patients

No excess hazard of death/MI and a low rate of stent thrombosis observed in DES patients at one-year

These findings support the use of DES in routine clinical practice

Extended follow-up is needed to determine incidence of very late stent thrombosis