Drug-Eluting and Bare Metal Stenting for Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction in Acute Myocardial Infarction in MassachusettsMassachusetts

Laura Mauri, Treacy S. Silbaugh, Robert E. Wolf, Katya Laura Mauri, Treacy S. Silbaugh, Robert E. Wolf, Katya Zelevinsky, Ann Lovett, Manu Varma, and Zelevinsky, Ann Lovett, Manu Varma, and Sharon-Lise T. NormandSharon-Lise T. Normand

Brigham and Women’s Hospital, Harvard Medical School, Brigham and Women’s Hospital, Harvard Medical School, Harvard School of Public Health all in Boston, MassachusettsHarvard School of Public Health all in Boston, Massachusetts

March 30, 2008March 30, 2008American College of Cardiology, ChicagoAmerican College of Cardiology, Chicago

Disclosure Information

Drug-Eluting and Bare Metal Stenting for Acute Myocardial Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction in MassachusettsInfarction in Massachusetts

The following relationships exist related to this presentation:

L Mauri Honoraria: Abbott, Boston Scientific, Cordis, MedtronicModest Level

T Silbaugh, R Wolf, K Zelevinsky, A Lovett, and SL Normand: Salary and research funding from Massachusetts Department of Public Health

M Varma No disclosures

Drug-Eluting and Bare Metal Stenting for Acute Drug-Eluting and Bare Metal Stenting for Acute Myocardial InfarctionMyocardial Infarction

We wish to thank Paul Dreyer, Ph.D. of the Massachusetts We wish to thank Paul Dreyer, Ph.D. of the Massachusetts Department of Public Health and the members of the Department of Public Health and the members of the Mass-DAC PCI Data Adjudication CommitteeMass-DAC PCI Data Adjudication Committee

Josh Krasnow, M.D.Josh Krasnow, M.D.Anthony Marks, M.D.Anthony Marks, M.D.Theo E. Meyer, M.D., Ph.D.Theo E. Meyer, M.D., Ph.D.Kathy Minahan, R.N.Kathy Minahan, R.N.Zoran Nedelijkovic, M.D.Zoran Nedelijkovic, M.D.Barbara Oxley, R.N.Barbara Oxley, R.N.Thomas C. Piemonte, M.D.Thomas C. Piemonte, M.D.Kenneth Rosenfield, M.D.Kenneth Rosenfield, M.D.Pinak B. Shah, M.D.Pinak B. Shah, M.D.Samuel J. Shubrooks Jr., M.D.Samuel J. Shubrooks Jr., M.D.James Waters, M.D.James Waters, M.D.Bonnie Weiner, M.D. Bonnie Weiner, M.D.

Kurt Barringhaus, M.D.Kurt Barringhaus, M.D.Clifford J. Berger, M.D.Clifford J. Berger, M.D.David Cohen, M.D.David Cohen, M.D.Angela Corey, R.N.Angela Corey, R.N.Jean Crossman, R.N.Jean Crossman, R.N.Daniel Fisher, M.D.Daniel Fisher, M.D.Joe Garasic, M.D.Joe Garasic, M.D.Jean-Pierre Geagea, M.D.Jean-Pierre Geagea, M.D.Gregory Giugliano, M.D.Gregory Giugliano, M.D.Kalon Ho, M.D.Kalon Ho, M.D.Alice Jacobs, M.D.Alice Jacobs, M.D.James Kirshenbaum, M.D.James Kirshenbaum, M.D.

Drug-Eluting and Bare Metal Stenting for Acute Drug-Eluting and Bare Metal Stenting for Acute Myocardial InfarctionMyocardial InfarctionBackgroundBackground

Acute myocardial infarction represents a large Acute myocardial infarction represents a large proportion of stenting procedures, and is the clinical proportion of stenting procedures, and is the clinical syndrome with the greatest documented benefit for PCIsyndrome with the greatest documented benefit for PCI

Yet patients with acute myocardial infarction (AMI) have Yet patients with acute myocardial infarction (AMI) have not been included in the major randomized trials not been included in the major randomized trials comparing drug eluting stents (DES) to bare metal stents comparing drug eluting stents (DES) to bare metal stents (BMS)(BMS)

And specific studies of AMI have been limited in size and And specific studies of AMI have been limited in size and study duration to detect adverse clinical events. study duration to detect adverse clinical events.

Drug-Eluting and Bare Metal Stenting for Acute Drug-Eluting and Bare Metal Stenting for Acute Myocardial InfarctionMyocardial Infarction ObjectivesObjectives

– To evaluate whether the use of DES is To evaluate whether the use of DES is associated with increased rates of death or MI associated with increased rates of death or MI compared with BMS in patients with acute compared with BMS in patients with acute myocardial infarctionmyocardial infarction

– To evaluate whether the use of DES is To evaluate whether the use of DES is associated with reduction in revascularization associated with reduction in revascularization compared with BMS in patients with acute compared with BMS in patients with acute myocardial infarctionmyocardial infarction

Drug-Eluting and Bare Metal Stenting for Acute Drug-Eluting and Bare Metal Stenting for Acute Myocardial InfarctionMyocardial Infarction Methods:Methods:

All PCI for NSTEMI or STEMI in Massachusetts non-All PCI for NSTEMI or STEMI in Massachusetts non-federal hospitals April 2003 – Sept. 30, 2004federal hospitals April 2003 – Sept. 30, 2004Clinical and procedural factors collected prospectively Clinical and procedural factors collected prospectively using ACC NCDR instrument and reported to Mass-DAC using ACC NCDR instrument and reported to Mass-DAC (State Dept of Public Health database)(State Dept of Public Health database)Mortality from hospital record, MA Registry of Vital Mortality from hospital record, MA Registry of Vital Records & Statistics, & Social Security websiteRecords & Statistics, & Social Security websiteMyocardial infarction and revascularization from Mass-Myocardial infarction and revascularization from Mass-DAC PCI and CABG data merged with hospital discharge DAC PCI and CABG data merged with hospital discharge datadataNon-Massachusetts residents excludedNon-Massachusetts residents excluded

Drug-Eluting and Bare Metal Stenting for Acute Drug-Eluting and Bare Metal Stenting for Acute Myocardial InfarctionMyocardial Infarction MethodsMethods

Patients assigned to DES or BMS groups based Patients assigned to DES or BMS groups based on treatment at index procedure on treatment at index procedure Patients treated with both types were excludedPatients treated with both types were excludedPropensity score matching Propensity score matching – Logistic regression to predict DES treatment Logistic regression to predict DES treatment

by up to 63 patient, procedural, hospital by up to 63 patient, procedural, hospital variablesvariables

– 1:1 caliper matching of DES to BMS patients 1:1 caliper matching of DES to BMS patients Primary outcomes: Matched risk differences for Primary outcomes: Matched risk differences for mortality, myocardial infarction and mortality, myocardial infarction and revascularization rates at 2 yearsrevascularization rates at 2 yearsPaired t-test, 2-sided alpha 0.05Paired t-test, 2-sided alpha 0.05

Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction

N=21,019 PCI Patients in N=21,019 PCI Patients in MassachusettsMassachusetts

April 1, 2003- September 30, 2004April 1, 2003- September 30, 2004Complete 2 year follow-upComplete 2 year follow-up

N=21,019 PCI Patients in N=21,019 PCI Patients in MassachusettsMassachusetts

April 1, 2003- September 30, 2004April 1, 2003- September 30, 2004Complete 2 year follow-upComplete 2 year follow-up

575 non-residents excluded575 non-residents excluded575 non-residents excluded575 non-residents excluded

183 administrative files not linkable183 administrative files not linkable183 administrative files not linkable183 administrative files not linkable

N=8,454 MI Patients N=8,454 MI Patients (40%) N=8,454 MI Patients N=8,454 MI Patients (40%)

N=4,016 N=4,016 DES Only PatientsDES Only Patients

N=4,016 N=4,016 DES Only PatientsDES Only Patients

N=3,200 N=3,200 BMS Only PatientsBMS Only Patients

N=3,200 N=3,200 BMS Only PatientsBMS Only Patients

480 patients with both 480 patients with both stent types excludedstent types excluded

480 patients with both 480 patients with both stent types excludedstent types excluded

N=7,696 PatientsN=7,696 Patients N=7,696 PatientsN=7,696 Patients

12,565 non-MI PCI patients12,565 non-MI PCI patients12,565 non-MI PCI patients12,565 non-MI PCI patients

28% PES28% PES28% PES28% PES 72% SES72% SES72% SES72% SES

Drug-Eluting and Bare Metal Stenting for Acute Drug-Eluting and Bare Metal Stenting for Acute Myocardial InfarctionMyocardial InfarctionPatient Characteristics before MatchPatient Characteristics before Match

DESDES(n = 4016)(n = 4016)

BMSBMS(n =3200)(n =3200)

p p valuevalue

Age – yrsAge – yrs 63.6 ±13.463.6 ±13.4 64.3 ±13.964.3 ±13.9 0.040.04

Female (%)Female (%) 33.0 33.0 33.0 33.0 0.910.91

Diabetes Mellitus (%)Diabetes Mellitus (%) 25.625.6 22.622.6 0.0040.004

Hyperlipidemia (%)Hyperlipidemia (%) 66.766.7 62.262.2 <0.001<0.001

Hypertension (%)Hypertension (%) 69.069.0 65.165.1 <0.001<0.001

Current Smoker (%)Current Smoker (%) 29.029.0 31.331.3 0.030.03

Prior PCI (%)Prior PCI (%) 14.014.0 12.812.8 0.130.13

Prior MI (%)Prior MI (%) 22.322.3 23.323.3 0.330.33

Prior CABG (%)Prior CABG (%) 8.38.3 9.89.8 0.0040.004

Drug-Eluting and Bare Metal Stenting for Acute Drug-Eluting and Bare Metal Stenting for Acute Myocardial InfarctionMyocardial InfarctionPatient Characteristics before MatchPatient Characteristics before Match

DESDES(n = 4016)(n = 4016)

BMSBMS(n =3200)(n =3200)

p p valuevalue

Congestive Heart Failure Congestive Heart Failure (%)(%) 9.49.4 10.510.5 0.110.11

Chronic Lung Disease Chronic Lung Disease (%)(%) 11.111.1 12.012.0 0.240.24

History of Neoplasm History of Neoplasm (%)(%) 2.22.2 3.03.0 0.020.02

History of GI Bleeding History of GI Bleeding (%)(%) 2.42.4 3.23.2 0.050.05

Chronic Renal Insufficiency (%)Chronic Renal Insufficiency (%) 6.16.1 6.76.7 0.300.30

Dialysis (%)Dialysis (%) 1.61.6 1.31.3 0.210.21

Clopidogrel Pretreatment (%)*Clopidogrel Pretreatment (%)* 34.934.9 32.332.3 0.020.02

GPIIb/IIIa Inhibitor Pretreatment (%)GPIIb/IIIa Inhibitor Pretreatment (%) 35.135.1 38.238.2 0.0070.007

*Although dual antiplatelet therapy (DAP) compliance data are not available, during the time period of entry to the study (4/03- 9/04) consensus recommendations were 4/03- 9/04) consensus recommendations were for 1m DAP for BMS and 3-6m for DES.for 1m DAP for BMS and 3-6m for DES.

Drug-Eluting and Bare Metal Stenting for Acute Drug-Eluting and Bare Metal Stenting for Acute Myocardial InfarctionMyocardial InfarctionProcedure Indications before MatchProcedure Indications before Match

DESDES(n = 4016)(n = 4016)

BMSBMS(n =3200)(n =3200)

p p valuevalue

MI typeMI type <0.001<0.001

STEMISTEMI 38.938.9 56.856.8

NSTEMINSTEMI 61.161.1 43.243.2

Procedure statusProcedure status <0.001<0.001

Urgent Urgent (%)(%) 47.547.5 35.435.4

Emergency/Salvage Emergency/Salvage (%)(%) 37.537.5 54.254.2

ThrombectomyThrombectomy 7.87.8 13.813.8 <0.001<0.001

Drug-Eluting and Bare Metal Stenting for Acute Drug-Eluting and Bare Metal Stenting for Acute Myocardial InfarctionMyocardial InfarctionProcedural Characteristics before MatchProcedural Characteristics before Match

DESDES(n = 4016)(n = 4016)

BMSBMS(n =3200)(n =3200)

p p valuevalue

Number of vessels treatedNumber of vessels treated 1.18 ± 0.431.18 ± 0.43 1.10 ± 0.321.10 ± 0.32 <0.001<0.001

Number of lesions treatedNumber of lesions treated 1.41 ± 0.701.41 ± 0.70 1.31 ± 0.601.31 ± 0.60 <0.001<0.001

Left anterior descending Left anterior descending (%)(%) 43.743.7 37.037.0 <0.001<0.001

Circumflex Circumflex (%)(%) 32.932.9 26.026.0 <0.001<0.001

Right coronary Right coronary (%)(%) 39.839.8 45.845.8 <0.001<0.001

Left main Left main (%)(%) 1.51.5 1.21.2 0.320.32

Saphenous vein graft Saphenous vein graft (%)(%) 3.73.7 6.16.1 <0.001<0.001

Arterial graft Arterial graft (%)(%) 0.10.1 0.20.2 0.720.72

Drug-Eluting and Bare Metal Stenting for Acute Myocardial Infarction

N=4,016 patients withN=4,016 patients withDES for MIDES for MI

N=4,016 patients withN=4,016 patients withDES for MIDES for MI

N=3,200 patients withN=3,200 patients withBMS for MIBMS for MI

N=3,200 patients withN=3,200 patients withBMS for MIBMS for MI

2,453 (61.1%)2,453 (61.1%)DES for NSTEMIDES for NSTEMI2,453 (61.1%)2,453 (61.1%)

DES for NSTEMIDES for NSTEMI

1,563 (38.9%)1,563 (38.9%) DES for STEMIDES for STEMI1,563 (38.9%)1,563 (38.9%) DES for STEMIDES for STEMI

1,382 (43.2%)1,382 (43.2%) BMS for NSTEMIBMS for NSTEMI

1,382 (43.2%)1,382 (43.2%) BMS for NSTEMIBMS for NSTEMI

1,818 (56.8%)1,818 (56.8%) BMS for STEMIBMS for STEMI1,818 (56.8%)1,818 (56.8%)

BMS for STEMIBMS for STEMI

Propensity score matched pairs

2629 MI2629 MI2629 MI2629 MI

1,221 NSTEMI1,221 NSTEMI1,221 NSTEMI1,221 NSTEMI

1,302 STEMI1,302 STEMI1,302 STEMI1,302 STEMI

1,221 NSTEMI1,221 NSTEMI1,221 NSTEMI1,221 NSTEMI

1,302 STEMI1,302 STEMI1,302 STEMI1,302 STEMI

2629 MI2629 MI2629 MI2629 MI

matched pairs

matched pairs

Drug-Eluting and Bare Metal Stenting for Acute Drug-Eluting and Bare Metal Stenting for Acute Myocardial InfarctionMyocardial InfarctionPatient Characteristics after MatchPatient Characteristics after Match

DESDES(n = 2629)(n = 2629)

BMSBMS(n =2629)(n =2629) % SD% SD

Age – yrsAge – yrs 64.764.7 64.264.2 0.00.0

Female (%)Female (%) 33.733.7 33.433.4 0.80.8

Diabetes Mellitus (%)Diabetes Mellitus (%) 22.422.4 22.922.9 -1.3-1.3

Hyperlipidemia (%)Hyperlipidemia (%) 62.162.1 63.663.6 -3.2-3.2

Hypertension (%)Hypertension (%) 66.166.1 66.766.7 -1.3-1.3

Current Smoker (%)Current Smoker (%) 31.031.0 30.830.8 0.30.3

Prior PCI (%)Prior PCI (%) 12.612.6 12.812.8 -0.9-0.9

Prior MI (%)Prior MI (%) 24.024.0 23.023.0 2.42.4

Prior CABG (%)Prior CABG (%) 9.09.0 8.88.8 0.50.5

*%SD = Percent Standardized DifferenceValues <10% reflect well-matched characteristics

Drug-Eluting and Bare Metal Stenting for Acute Drug-Eluting and Bare Metal Stenting for Acute Myocardial InfarctionMyocardial InfarctionPatient Characteristics after MatchPatient Characteristics after Match

DESDES(n = 2629)(n = 2629)

BMSBMS(n =2629)(n =2629) %SD%SD

Congestive Heart Failure (NYHA 3-4)Congestive Heart Failure (NYHA 3-4) 9.29.2 8.38.3 3.13.1

Chronic Lung Disease Chronic Lung Disease (%)(%) 12.912.9 12.012.0 2.92.9

History of Neoplasm History of Neoplasm (%)(%) 2.92.9 2.72.7 1.41.4

History of GI Bleeding History of GI Bleeding (%)(%) 3.23.2 3.23.2 0.20.2

Chronic Renal Insufficiency (%)Chronic Renal Insufficiency (%) 6.66.6 6.56.5 0.30.3

Dialysis (%)Dialysis (%) 1.41.4 1.51.5 -1.0-1.0

Clopidogrel Preadminstered (%)Clopidogrel Preadminstered (%) 29.629.6 31.231.2 -3.5-3.5

GPIIb/IIIa Inhibitor Preadminstered (%)GPIIb/IIIa Inhibitor Preadminstered (%) 38.838.8 37.737.7 2.42.4

*%SD = Percent Standardized DifferenceValues <10% reflect well-matched characteristics

Drug-Eluting and Bare Metal Stenting for Acute Drug-Eluting and Bare Metal Stenting for Acute Myocardial InfarctionMyocardial InfarctionProcedure Indications after MatchProcedure Indications after Match

DESDES(n = 2629)(n = 2629)

BMSBMS(n =2629)(n =2629)

MI typeMI type

STEMISTEMI 55.455.4 50.550.5

NSTEMINSTEMI 44.644.6 49.549.5

Procedure statusProcedure status

Urgent Urgent (%)(%) 37.637.6 40.240.2

Emergency/Salvage Emergency/Salvage (%)(%) 51.851.8 47.847.8

ThrombectomyThrombectomy 9.19.1 8.88.8

Drug-Eluting and Bare Metal Stenting for Acute Drug-Eluting and Bare Metal Stenting for Acute Myocardial InfarctionMyocardial InfarctionProcedural Characteristics after MatchProcedural Characteristics after Match

DESDES(n = 2629)(n = 2629)

BMSBMS(n =2629)(n =2629) %SD%SD

Multilesion treatmentMultilesion treatment

2 lesions2 lesions 20.020.0 21.321.3 -3.3-3.3

3 lesions3 lesions 3.73.7 4.74.7 -4.9-4.9

4 lesions4 lesions 0.70.7 0.80.8 -1.8-1.8

Target vesselTarget vessel

Left circumflexLeft circumflex 26.426.4 28.228.2 -3.9-3.9

Right coronary Right coronary 44.844.8 43.643.6 2.52.5

Left mainLeft main 1.51.5 1.41.4 1.01.0

Saphenous vein graftSaphenous vein graft 5.15.1 5.05.0 0.50.5

Arterial graftArterial graft 0.20.2 0.20.2 0.00.0

*%SD = Percent Standardized DifferenceValues <10% reflect well-matched characteristics

-6% -3% 0% 3% 6%

Drug-Eluting & Bare Metal Stenting in Massachusetts Drug-Eluting & Bare Metal Stenting in Massachusetts Risk Differences in Matched MI Patient Groups at 2 yearsRisk Differences in Matched MI Patient Groups at 2 years

Risk Difference (95% CI), DES v. BMSRisk Difference (95% CI), DES v. BMS

Death Recurrent MI

NSTEMI NSTEMI

MIMI

STEMI STEMI

n=2629 pairs

n=1221 pairs

n=1302 pairs

-6% -3% 0% 3% 6%

FavorsDES

FavorsBMS

-2.7% [-4.5%, 0%] P=0.002

-1.9% [-4.6%, 0.9%] P=0.18

-3.1% [-5.4%, -0.8%] P=0.009

FavorsDES

FavorsBMS

-1.5% [-3.1%, 0.2%]P=0.08

-2.4% [-5.0%, 0.3%]P=0.07

-1.6% [-3.7%, 0.5%]P=0.127

Drug-Eluting & Bare Metal Stenting in Massachusetts Drug-Eluting & Bare Metal Stenting in Massachusetts Risk Differences in Matched MI Patient Groups at 2 yearsRisk Differences in Matched MI Patient Groups at 2 years

Risk Difference (95% CI), DES v. BMSRisk Difference (95% CI), DES v. BMS

Revascularization TVR

-10% -5% 0% 5% 10%

FavorsDES

FavorsBMS

-5.3% [-7.4%, -3.2%]P<0.001

-5.3% [-8.4%, -2.3%]P<0.001

-6.0% [-9.0%, -3.0%]P<0.001

-10% -5% 0% 5% 10%

FavorsDES

FavorsBMS

-3.6% [-5.2%, -2.0%]P<0.001

-2.9% [-5.4%, -0.5%]P=0.02

-3.5% [-5.8%, -1.3%]P=0.002

NSTEMI NSTEMI

MIMI

STEMI STEMI

n=2629 pairs

n=1221 pairs

n=1302 pairs

Drug-Eluting & Bare Metal Stenting in Massachusetts Drug-Eluting & Bare Metal Stenting in Massachusetts 2-Year Outcome in Matched 2-Year Outcome in Matched MIMI Patients PatientsFigure 2

No. at Risk 0 30 180 365 730 DES 2629 2618 2550 2484 2433 BMS 2629 2614 2512 2431 2373

No. at Risk 0 30 180 365 730 DES 2629 2604 2483 2368 2283 BMS 2629 2592 2430 2285 2192

No. at Risk 0 30 180 365 730

DES 2629 2624 2427 2243 2127 BMS 2629 2618 2372 2091 1957

No. at Risk 0 30 180 365 730

DES 2629 2624 2492 2380 2291 BMS 2629 2618 2443 2250 2148

DES BMS

DES BMS

Death MI A. B.

Revascularization TVR C. D. DES BMS

DES BMS

2373237324312431251225122614261426292629BMSBMS2433243324842484255025502618261826292629DESDES

730730365365180180303000No. at Risk

2192219222852285243024302592259226292629BMSBMS2283228323682368248324832604260426292629DESDES

730730365365180180303000No. at Risk

No. at Risk 00 3030 180180 365365 730730

DESDES 26292629 26242624 24272427 22432243 21272127BMSBMS 26292629 26182618 23722372 20912091 19571957

No. at Risk 00 3030 180180 365365 730730DESDES 26292629 26242624 24922492 23802380 22912291BMSBMS 26292629 26182618 24432443 22502250 21482148

Death Recurrent MI

Revasc TVR

BMS

DES

Drug-Eluting and Bare Metal Stenting for MI in Drug-Eluting and Bare Metal Stenting for MI in Massachusetts Massachusetts Sensitivity analysesSensitivity analyses

Match adjusting for time on market yields consistent conclusionsMatch adjusting for time on market yields consistent conclusions

STEMI group exclusion of programs without surgery on site, or STEMI group exclusion of programs without surgery on site, or patients with >24h presentation, yields consistent conclusionspatients with >24h presentation, yields consistent conclusions

No evidence of a 2 day clinical or statistical significant benefit No evidence of a 2 day clinical or statistical significant benefit which is supportive of no residual confoundingwhich is supportive of no residual confounding

• 2 day mortality DES-BMS = -0.5% [-1.0,+0.04]• 2 year mortality DES-BMS = -2.7% [-4.5%, 0%]

Complete 2 year data are available for 7216 unique Complete 2 year data are available for 7216 unique DES or BMS DES or BMS procedures for MI in Massachusetts from April 2003- September procedures for MI in Massachusetts from April 2003- September 2004.2004.

Propensity matched analysis of 5258 patients with MI Propensity matched analysis of 5258 patients with MI demonstrated:demonstrated:

No increase in rates of death, or myocardial infarction associated No increase in rates of death, or myocardial infarction associated with DES as compared to BMS use at 2 years overall and for the with DES as compared to BMS use at 2 years overall and for the subsets of STEMI and NSTEMIsubsets of STEMI and NSTEMI

– Although our aim was to detect a signal of harm, we observed lower 2y mortality Although our aim was to detect a signal of harm, we observed lower 2y mortality in STEMI patients treated with DESin STEMI patients treated with DES

A lower rate of repeat revascularization in patients treated with A lower rate of repeat revascularization in patients treated with DES compared with BMS overall and for both subsets.DES compared with BMS overall and for both subsets.

Drug-Eluting and Bare Metal Stenting in Drug-Eluting and Bare Metal Stenting in Massachusetts Massachusetts ConclusionsConclusions