outcomes following coronary stenting: a national study of long term, real-world outcomes of...
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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
13
9
6
21 20
4 3 3 30
5
10
15
20
25
Death MI Revasc Bleeding Stroke
BMS
DES
Events Requiring Rehospitalization
Rat
e /
100
pat
ien
ts
DES and BMS Event Rates:30-month Adjusted
0
5
10
15
20
25
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
e /
100
pat
ien
ts
Landmark Display: Mortality
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0 6 12 18 24 30
Months
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t R
ate
BMS DES
Landmark Display: Mortality
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ate
BMS DES BMS_6 DES_6
Landmark Display: Mortality
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Months
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t R
ate
BMS DES BMS_6 DES_6 BMS_12 DES_12
Landmark Analysis: MI
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nt R
ate
BMS DES BMS_6 DES_6 BMS_12 DES_12
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0 6 12 18 24 30
Months
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
0
5
10
15
20
25
30BMS
DES
Un
ad
jus
ted
ra
tes/
100
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
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