Outcomes Following Coronary Stenting:A National Study of Long Term,

Real-World Outcomes of Bare-Metal and Drug-Eluting Stents

Pamela S. Douglas, J. Matthew Brennan, Kevin J. Anstrom, Eric L. Eisenstein, David Dai, Ghazala Haque, David F. Kong, Ralph

Brindis, Art Sedrakyan, David Matchar, Eric D. Peterson

Duke Clinical Research InstituteDuke University Medical Center

Funding and Disclosures

Disclosures: ( See www.dcri.duke.edu for full information) Pamela S. Douglas: None relevant J. Matthew Brennan: None Kevin Anstrom: Research Support from AstraZeneca, Bristol Myers Squibb,

Eli Lilly and Medtronic; consultant for Johnson & Johnson and Pfizer. Eric L. Eisenstein: Research Support from Medtronic Vascular and Eli Lilly David Dai: None Ghazala Haque: None David F. Kong: None relevant Ralph Brindis: None Art Sedrakyan: None David Matchar: None relevant Eric D. Peterson: Research Support from BMS/Sanofi and Merck/Schering

Sponsor and funding: AHRQ CV Research Consortium

Additional support: ACC-NCDR

Background

Clinical trials demonstrate reduced restenosis with drug eluting coronary stents (DES) compared to bare metal stents (BMS)

However, some trials and registries have reported late stent thrombosis and higher mortality with DES

Questions remain regarding the effectiveness and safety of DES in the real world and among understudied patient populations

Goal and Population

Goal To examine comparative effectiveness and safety of

DES vs BMS in a national PCI cohort

Study population • All PCI pts > 65 yo in NCDR CathPCI 1/04-12/06

• Follow up obtained through linkage to CMS inpatient claims data using indirect identifiers; 76% matched

Final cohort 262,700 pts 83% DES; 46% Cypher, 55% Taxus

Analysis

30 month outcomes Death, MI, Stroke, Revascularization, Major bleeding Overall and in important subgroups

Outcomes adjustments Inverse propensity weighted model (102 covariates) Cox proportional hazards model (60 covariates)

Sensitivity analyses• Results in ‘RCT-like’ population• Non-CV ‘cause’ of death

Patient Characteristics DES (217,675) vs BMS (45,025)

Unadjusted IPW AdjustedDES BMS DES BMS

Age 74.5 75.3* 74.7 74.8

Female 43% 40%* 43% 43%

Caucasian 90% 91%* 90% 90%

Diabetes  32% 32%  32% 32%

Renal Failure  6% 8%*  7% 7%

Hypertension 80% 80%* 80% 81%

Prior PCI 28% 26%* 28% 28%

Prior CABG 22% 28%* 23% 23%

Urgent Status 38% 36%* 37% 38%

STEMI 10% 16%* 11% 11%

*p<0.0001 DES vs BMS

DES and BMS Event Rates:30-month Unadjusted

18

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21 20

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Death MI Revasc Bleeding Stroke

BMS

DES

Events Requiring Rehospitalization

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DES and BMS Event Rates:30-month Adjusted

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Death MI Revasc Bleeding Stroke

BMS

DES

HR = 0.91(0.85,0.98)

HR = 0.96(0.88,1.04)

HR = 0.75(0.73,0.77)

HR = 0.76(0.72,0.80)

HR = 0.91(0.89,0.94)

Rat

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100

pat

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ts

Landmark Display: Mortality

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BMS DES

Landmark Display: Mortality

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BMS DES BMS_6 DES_6

Landmark Display: Mortality

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Landmark Analysis: MI

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STEMI HR = 0.78NSTEMI HR = 0.73

Subgroup Analyses

MalesFemalesAge >= 75Age < 75Off LabelNo DiabetesDiabetes / non-insulin depDiabetes / insulin depElectiveUrgentSTEMINo Renal FailureNon-dialysis RFDialysisPrior PCINo Prior PCIPrior CABGNo Prior CABGCHF (current status)No CHF (current status)Prior MINo Prior MI1 Vessel Disease2 Vessel Disease3 Vessel Disease2004 PCI2005 PCI2006 PCI

Overall

.5 .6 .75 1 1.25 1.5 2

Death

MalesFemalesAge >= 75Age < 75Off LabelNo DiabetesDiabetes / non-insulin depDiabetes / insulin depElectiveUrgentSTEMINo Renal FailureNon-dialysis RFDialysisPrior PCINo Prior PCIPrior CABGNo Prior CABGCHF (current status)No CHF (current status)Prior MINo Prior MI1 Vessel Disease2 Vessel Disease3 Vessel Disease2004 PCI2005 PCI2006 PCI

Overall

.5 .6 .75 1 1.25 1.5 2

Myocardial InfarctionMalesFemalesAge >= 75Age < 75Off LabelNo DiabetesDiabetes / non-insulin depDiabetes / insulin depElectiveUrgentSTEMINo Renal FailureNon-dialysis RFDialysisPrior PCINo Prior PCIPrior CABGNo Prior CABGCHF (current status)No CHF (current status)Prior MINo Prior MI1 Vessel Disease2 Vessel Disease3 Vessel Disease2004 PCI2005 PCI2006 PCI

Overall

.5 .6 .75 1 1.25 1.5 2

RevascularizationDeath MI Revasc

Favors DES

Sensitivity Analysis:Patient Selection

RCT - like population N = 49,355 (19%) ‘Inclusion’ criteria

Elective PCI, < 2 stents Native vessel, de novo Class A or B lesions Lesion length, diameter ASA, clopidogrel OK No CKD

Death

Death or MI

MI

Revascularization

Stroke

Bleed

Overall

RCT Population

Overall

RCT Population

Overall

RCT Population

Overall

RCT Population

Overall

RCT Population

Overall

RCT Population

.5 .6 .75 1 1.25 1.5 2

Favors DES

Sensitivity Analysis: Device Selection ‘Cause of Death’ in DES v BMS

Using 1º hosp dx, ‘cause’ extracted in 90% deaths HR 0.80 favoring DES for CHF/MI death HR 0.74 favoring DES Non CV death ‘Sicker’ patients may preferentially receive BMS

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Potential Limitations

Medicare, NCDR data sources All patients were > 65 yo, inpatients,

NCDR sites (n=650) No clinical data available for bleeding,

revascularization, stent thrombosis No information on follow-up medications

Observational data: potential for bias, unmeasured confounders

Conclusions Linkage of clinically rich NCDR data to claims

data is feasible; Data analysis allows a robust, longitudinal assessment of clinical effectiveness

Comparing outcomes of DES to BMS at 30 mo: No major DES safety concerns Lower death and MI rates in DES patients Slightly lower revascularization, bleeding rates Similar stroke rates

Results consistent among all patient subgroups Caveat: The apparent ‘benefit’ of DES may be affected

by selection bias and unmeasured confounders present in this real world cohort

THANK YOU

Study PopulationAll PCI admissions for patients who had some stent implantation

450,242 PCI admissions, 662 sites, 390,973 patients

CMS Matched290,438 PCI admissions, 650 sites, 290,438 patients

Exclude patients w index stent application w not during Fee- For-Service (FFS) enrollment14,225 PCI admissions, 597 sites, 14,225 pts

Patients w index stent application during FFS enrollment

276,213 PCI admissions, 650 sites, 276,213 pts

Exclude admissions with both DES and BMS12,822 PCI admissions, 583 sites, 12,822 pts

Admissions with either DES only or BMS only263,391 PCI admissions, 650 sites, 263,391 pts

Exclude records with missing candidate variables and time-to-censor out of range [0-

1096 days]

Final study population262,700 PCI admissions, 650 sites,

262,700 patients

CMS Matched vs Not MatchedPatient Clinical Characteristics

Total (387,849)

CMS-Matched (290,438)

CMS-Not-Matched (97,411)

Age 74.3 ± 6.5 74.6 ± 6.5 73.6 ± 6.3

Female 41.3% 42.4% 38.2%

Caucasian 88.8% 90.3% 84.5%

Diabetes

– Non-insulin 23.1% 22.9% 23.7%

– Insulin 9.5% 9.6% 9.1%

Prior Renal Failure

– Non-dialysis 4.9% 5.0% 4.4%

– Dialysis 1.6% 1.6% 1.4%

Hypertension * 80.3% 80.3% 80.4%

Prior PCI 28.1% 27.9% 28.4%

Prior CABG 22.8% 23.2% 21.8%

CMS Match vs Not Matched Patient Clinical Characteristics

Total (387,849)

CMS Matched (290,438)

CMS Not-Matched (97,411)

Status

– Urgent 15.2% 15.6% 14.0%

– STEMI 11.2% 11.6% 10.0%

Number of Diseased Vessels

– One 41.7% 41.3% 43.0%

– Two 31.4% 31.5% 31.1%

– Three

DES

22.9% 23.2% 22.1%

– Some Cypher 46.1% 46.2% 46.0%

– Some Taxus 55.5% 55.4% 55.8%

– Some Off-label 70.6% 70.2% 71.9%

Unmeasured Confounder: Post-PCI Clopidogrel Use

Used published Duke data for clopidogrel use and survival benefit to correct HR for death:

Prevalence DES use = 50%, BMS use = 20% @ 12 mo Clopidogrel benefit: 50% death @ 12 mo in DES, BMS

HR death corrects from 0.75 to 0.90

W/o clopidogrel use HR = 0.75

With use @ 50%, 20%

cHR = 0.90

BMS family of curves: 0 to 50% use

JAMA 2007 297:159Biometrics 1998 54:948

Comparability with OtherRegistry Data – Mortality

Historic Control

Contemporary Control

Hannan

Malenka

Groeneveld (medicare)

Lagerqvist

Stone

Spaulding

Anstrom

Marzocci

Ajani

Tu*

Shishehbor

Austin (off label)

Groeneveld (medicare)

.5 .6 .75 1 1.25 1.5 2

Favors DES

Favors BMS