Bare Metal Stents vs. DrugBare Metal Stents vs. Drug--Eluting Stents for STEMI:Eluting Stents for STEMI:

Is it Settled? Is it Settled?

Ajay J. Ajay J. KirtaneKirtane, MD, SM, MD, SM

Columbia University Medical Center /Columbia University Medical Center /New York Presbyterian HospitalNew York Presbyterian Hospital

Conflict of Interest DisclosureConflict of Interest Disclosure

•• Ajay J. KirtaneAjay J. Kirtane

–– In the last 12 months, I have received In the last 12 months, I have received honoraria/consultancy fees from Abbott honoraria/consultancy fees from Abbott Vascular, Boston Scientific, and Vascular, Boston Scientific, and Medtronic CardioVascularMedtronic CardioVascular

–– OffOff--label use will be discussedlabel use will be discussed

DES vs. BMS in STEMI:Why the Debate?

•• STEMI patients have the highest thrombotic STEMI patients have the highest thrombotic risk (potential for worse safety)risk (potential for worse safety)•• Worsened healing response after stenting?Worsened healing response after stenting?•• Greater potential for malapposition and/or Greater potential for malapposition and/or

underexpansionunderexpansion•• Highest ST rates, meeting patient “under Highest ST rates, meeting patient “under

the gun”the gun”•• STEMI lesions have lower restenosis rates STEMI lesions have lower restenosis rates

(potential for less DES efficacy)(potential for less DES efficacy)•• Less plaque, ISR less manifestLess plaque, ISR less manifest

Distinction between AMI andDistinction between AMI andNonNon--AMI LesionsAMI Lesions

Culprit siteCulprit site

Neointima

NC

Rupture siteNeointima

NC

Fibroatheroma culprit site (control)

AMI lesionAMI lesionPost stentPost stent

Stable lesionStable lesionPost stentPost stent

Delayed Arterial Healing with DES in AMI

Persistent fibrin deposition and uncovered struts in AMI compared to stable lesions treated with DES

Nakazawa and Virmani et al. Circulation 2008

AMIwith rupture

(n=17)

Stable with FA(n=18)

p valueAMI vs. Stable

Neointimal thickness, Neointimal thickness, mmmm

0.04(0.02, 0.09)

0.11(0.07, 0.21)

0.008

Strut with fibrin Strut with fibrin deposition, %deposition, % 63 ± 28 36 ± 27 0.008

Strut with Strut with inflammation, %inflammation, % 35 (27, 49) 17 (7, 25) 0.003

Uncovered strut, %Uncovered strut, % 49 (16, 96) 9 (0, 39) 0.01

Pathologic Assessment at Culprit SitePathologic Assessment at Culprit Site(AMI vs. Stable patients)(AMI vs. Stable patients)

Nakazawa and Virmani et al., Circulation 2008

HORIZONSHORIZONS--AMI IVUS SubstudyAMI IVUS Substudy

Post-Stent Follow-up

PES

BMS

• PES reduced net volume obstruction compared to BMS

• PES was associated with more late malapposition compared to BMS (29.6% vs. 7.9%, p<0.001)

402 patients, 446 lesions with serial IVUS data

Maehara A et al, Circulation 2009

Stent ThrombosisPatient, Procedure, DevicePatient, Procedure, Device

StentStentThrombosisThrombosisProcedure

• Lesion pre/post• Stent Expansion• Flow/Runoff

Patient Factors• Higher Risk (Syndrome, Comorbidities)• Adjunctive therapies• AP Adherence and/or Responsiveness

Device•• Polymer Polymer • Drug• Surface

HR (95% CI)HR (95% CI) P valueP value

LateLate

STEMISTEMI 5.5 (3.55.5 (3.5––7.6)7.6) <0.0001 <0.0001

LADLAD 3.0 (2.03.0 (2.0––4.4)4.4) <0.0001 <0.0001

Stent length (per mmStent length (per mm­­)) 1.07 (1.051.07 (1.05––1.09)1.09) <0.0001<0.0001

The Spanish ESTROFA RegistryThe Spanish ESTROFA Registry23,500 pts treated w/DES at 20 Spanish hospitals from 200223,500 pts treated w/DES at 20 Spanish hospitals from 2002––06; 63% 06; 63%

PES, 37% SES. Dual antiplatelet Rx for PES, 37% SES. Dual antiplatelet Rx for 8 8 ±± 3 months. 3 months. 1.3% ST rate at median FU 22 (11, 32) mos ; 2.0% ST at 3 yrs1.3% ST rate at median FU 22 (11, 32) mos ; 2.0% ST at 3 yrs

Multivariate Predictors of Stent Thrombosis (n=14,120)Multivariate Predictors of Stent Thrombosis (n=14,120)

de la Torre Hernandez JM et al. de la Torre Hernandez JM et al. JACCJACC 2008;51:9862008;51:986--9090

Impact of Thrombus Burden with DES in AMIImpact of Thrombus Burden with DES in AMI792 STEMI Patients with DES

Follow-Up (months)

Large Thrombus Burden

Small Thrombus Burden

Total Population

12

8.2%

3.2%

1.3%

9

6

3

0

0 1 3 6 9 12 15 18 21 24

Sianos G et al, J Am Coll Cardiol 2007; 50:573-83

Rate of IRA-STSmall Large

Final TIMI 3 94.9% 83.6%*

TMPG-3 53.2% 35.4%*

No-reflow 0.5% 4.0%*

Distal Embol. 3.5% 17.3%*

*P<0.001

Stent Thrombosis at 5 yearsStent Thrombosis at 5 yearsARC definite, probable, possibleARC definite, probable, possible

0 200 400 600 800 1000 1200 1400 1600 1800 2000

Days after Randomization

40

30

20

10

0

Pro

bab

ility of A

RC

Sten

t Th

rom

bo

sis (%)

Tirofiban-SES Abciximab-BMS

Hazard Ratio 1.13[95% CI: 0.44-2.9]; p=0.78

8%8%7%7%

J Am Coll Cardiol in pressJ Am Coll Cardiol in press

TwoTwo--Year Stent ThrombosisYear Stent Thrombosis(ARC Definite or Probable)(ARC Definite or Probable)

p= 0.99p= 0.99

HR [95%CI]=HR [95%CI]=1.00 [0.66, 1.51]1.00 [0.66, 1.51]

4.1%4.1%4.1%4.1%

Sten

t Thr

ombo

sis

(%)

Sten

t Thr

ombo

sis

(%)

00

11

22

33

44

55

66 TAXUS DES (n=2257)TAXUS DES (n=2257)EXPRESS BMS (n=749)EXPRESS BMS (n=749)

00 33 66 99 1212 1515 1818 2121 2424

22382238 21082108 20612061 19981998 16611661744744 696696 681681 661661 547547

Number at riskNumber at riskTAXUS DESTAXUS DESEXPRESS BMSEXPRESS BMS

MonthsMonths

0.0 2.0 4.0 6.0 8.0

CYPHER (n=251)

BMS (n=250)

Early (0 to 30 days) Very Late (> 1yr)

11(4.4%)

Stent Thrombosis (%)

12(4.8%)

9(3.6%)

6(2.4%)

3(1.2%)

5 (2.0%)

TYPHOON: ARC Definite/Probable Stent TYPHOON: ARC Definite/Probable Stent Thrombosis at 4 YearsThrombosis at 4 Years

P = 0.83

PES N=310

BMS N=309

HR (95% CI) P

Definite ST30 days – 1 year 1 (0.3%) 0 (0.0%)

1 year – 5 years 7 (2.5%) 2 (0.7%)

Total 8 (2.9%) 2 (0.8%) 3.95 (0.81 – 18.61) 0.06

Definite or Probable ST30 days – 1 year 2 (0.7%) 0 (0.0%)

1 year – 5 years 7 (2.5%) 3 (1.1%)

Total 9 (3.2%) 3 (1.1%) 2.97 (0.80 – 12.97) 0.09

5-Year LST and VLST

Incidences were estimated from the Kaplan-Meier curves

Vink, ACC/I2 2010

Impact of premature thienopyridine discontinuation: The PREMIER registry

500 pts with AMI undergoing primary PCI with DES at 19 U.S. medical centers, alive and well at 30 days

Spertus JA et al. Circulation 2006;113:2803Spertus JA et al. Circulation 2006;113:2803--9.9.Spertus JA et al. Circulation 2006;113:2803Spertus JA et al. Circulation 2006;113:2803--9.9.

68 (13.6%) were no longer taking 68 (13.6%) were no longer taking prescribed thienopyridines at 30 daysprescribed thienopyridines at 30 days

7.5

0.70

2

4

6

8

10

1 Ye

ar M

orta

lity

(%) D/C thienopyridine at 30 days

Taking thienopyridine at 30 days

P<0.0001P<0.0001Propensity Propensity adjusted for adjusted for

reasons to d/c reasons to d/c thien: HR = thien: HR = 9.02 9.02 (1.3(1.3--60.660.6), P=), P=0.020.02

Death/MI Related to Delays in Filling Clopidogrel Prescription after DES

Of 7,402 patients, 16% did not fill a clopidogrel prescription on day of discharge (median delay of 3 days)

Ho et al, Circ Cardiovasc Qual Outcomes 2010Ho et al, Circ Cardiovasc Qual Outcomes 2010Ho et al, Circ Cardiovasc Qual Outcomes 2010Ho et al, Circ Cardiovasc Qual Outcomes 2010

Delay

No Delay

DES in AMI Meta-Analysis

1 10 1000.10.01

Mortality (RCTs)Di Lorenzo et al.STRATEGYPASSIONTYPHOONBASKET-AMISELECTIONSESAMIDiaz de la Llera et al.DEDICATION StentHAAMU-STENTMISSIONHORIZONS-AMI StentMULTISTRATEGY

Overall

Favors DES Favors BMS

Relative Risk (95% CI)

0.89 (0.70 - 1.14)

I2 = 0%

Brar et al. JACC 2009; 53(18)Brar et al. JACC 2009; 53(18)

1 10 1000.10.01

Stent Thrombosis (RCTs)

Di Lorenzo et al.STRATEGYBASKET-AMIPASSIONTYPHOONDEDICATION StentHAAMU-STENTMISSIONSELECTIONDiaz de la Llera et al.HORIZONS-AMI StentMULTISTRATEGY

Overall

Favors DES Favors BMS

Relative Risk (95% CI)

0.97 (0.73 - 1.28)

I2 = 0%

Brar et al. JACC 2009; 53(18)Brar et al. JACC 2009; 53(18)

DES in AMI Meta-Analysis

Massachusetts State RegistryMassachusetts State Registry

Mauri L et al. Mauri L et al. NEJMNEJM 2008;359:13302008;359:1330--4242

22--year mortality (propensity adjusted) in 1298 matched pairs year mortality (propensity adjusted) in 1298 matched pairs (2596 pts) with STEMI at 21 hospitals between 4/03(2596 pts) with STEMI at 21 hospitals between 4/03––9/049/04

11.6%11.6%8.5%8.5%

P=0.008P=0.008

DrugDrug--Eluting StentEluting StentNo. at riskNo. at risk 12981298 12891289 12501250 12271227 12131213Cum. incidence (%)Cum. incidence (%) 0.70.7 3.73.7 5.55.5 6.56.5 8.58.5

BareBare--Metal StentMetal StentNo. at riskNo. at risk 12981298 12921292 12231223 11941194 11731173Cum. incidence (%)Cum. incidence (%) 0.50.5 5.85.8 8.08.0 9.69.6 11.611.6

Days after Initial ProcedureDays after Initial Procedure

Dea

th (a

djus

ted)

(%)

Dea

th (a

djus

ted)

(%)

3030

2020

1010

0000 3030 180180 365365 730730

BMS (n=1298)BMS (n=1298)

DES (n=1298)DES (n=1298)

1% mortality difference at 2 days1% mortality difference at 2 days2.1% mortality2.1% mortality difference at 30 daysdifference at 30 days

DES vs. BMS in STEMI:Case Closed?

•• Despite higher theoretical risks of Despite higher theoretical risks of delayed healing, malapposition, and delayed healing, malapposition, and other potential risks…other potential risks…•• Overall rates of ST and other clinical Overall rates of ST and other clinical

safety outcomes have been similar for safety outcomes have been similar for BMS and DESBMS and DES

•• So what about efficacy?So what about efficacy?

1 10 1000.10.01

Target Vessel Revascularization (RCTs)Di Lorenzo et al.STRATEGYBASKET-AMIPASSIONTYPHOONSELECTIONSESAMIDiaz de la Llera et al.DEDICATION StentHAAMU-STENTMISSIONHORIZONS-AMI StentMULTISTRATEGY

Overall

Favors DES Favors BMS

Relative Risk (95% CI)

0.44 (0.35 - 0.55)

56%REDUCTION

p < 0.001

I2 = 26%

Brar et al. JACC 2009; 53(18)Brar et al. JACC 2009; 53(18)

DES in AMI Meta-Analysis

TYPHOON4-Year Follow-Up of SES vs. BMS for AMI

Conclusion:Conclusion: At 4 years, SES still maintain their initial At 4 years, SES still maintain their initial advantage in terms of revascularization rates over BMS.advantage in terms of revascularization rates over BMS.

Spaulding C. Presented at: EuroPCR 2009.May 19-22, 2009.

4-Year Outcomes

Cyphern = 251

BMSn = 250 P Value

TLR (%) 7.2 15.2 0.005

MI (%) 4.8 4.0 0.83

Death (%) 4.0 6.4 0.23

22572257 21322132 20982098 20692069 18681868749749 697697 675675 658658 603603

Number at riskNumber at riskTAXUS DESTAXUS DESEXPRESS BMSEXPRESS BMS

Primary Efficacy Endpoint: Primary Efficacy Endpoint: Ischemic TLRIschemic TLR

Isch

emic

TLR

(%)

Isch

emic

TLR

(%)

00

11

22

33

44

55

66

77

88

99

1010

Time in MonthsTime in Months00 11 22 33 44 55 66 77 88 99 1010 1111 1212

7.5%7.5%

4.5%4.5%

Diff = Diff = --3.0%3.0%HR = HR = 0.590.59P=0.002P=0.002

TAXUS DES (n=2257)TAXUS DES (n=2257)EXPRESS BMS (n=749)EXPRESS BMS (n=749)

Which is more impressive?

1. 41% reduction in ischemic TLR

2. Need to treat 33 patients with DES vs. BMS to prevent one TLR event

Primary Efficacy Endpoint: Primary Efficacy Endpoint: Ischemic TLRIschemic TLR

P<0.001P<0.001

HR [95%CI]=HR [95%CI]=0.58 [0.44, 0.76]0.58 [0.44, 0.76]

6.8%6.8%

11.6%11.6%Is

chem

ic T

LR (%

)Is

chem

ic T

LR (%

)

00

33

66

99

1212

1515 TAXUS DES (n=2257)TAXUS DES (n=2257)EXPRESS BMS (n=749)EXPRESS BMS (n=749)

22572257 21052105 20412041 19491949 16181618749749 677677 654654 611611 507507

00 33 66 99 1212 1515 1818 2121 2424

Number at riskNumber at riskTAXUS DESTAXUS DESEXPRESS BMSEXPRESS BMS

MonthsMonths

Primary Efficacy Endpoint: Primary Efficacy Endpoint: Ischemic TLRIschemic TLR

22572257 21052105 20412041 19491949 16181618749749 677677 654654 611611 507507

P<0.001P<0.001

HR [95%CI]=HR [95%CI]=0.58 [0.44, 0.76]0.58 [0.44, 0.76]

6.8%6.8%

11.6%11.6%Is

chem

ic T

LR (%

)Is

chem

ic T

LR (%

)

00

33

66

99

1212

1515

00 33 66 99 1212 1515 1818 2121 2424

TAXUS DES (n=2257)TAXUS DES (n=2257)EXPRESS BMS (n=749)EXPRESS BMS (n=749)

Number at riskNumber at riskTAXUS DESTAXUS DESEXPRESS BMSEXPRESS BMS

MonthsMonths

p= 0.002p= 0.002

11--yr HR [95%CI]=yr HR [95%CI]=0.60 [0.43, 0.84]0.60 [0.43, 0.84]

13 mo angio FU

11--Year TLR According to BMS Risk ScoreYear TLR According to BMS Risk Score(N=2915)(N=2915)

N=946 (32.5%) N=1520 (52.1%) N=449 (15.4%)

Safety of DES vs. BMS in STEMI:Case Closed?

•• Despite higher theoretical risks of delayed Despite higher theoretical risks of delayed healing, malapposition, and other potential healing, malapposition, and other potential safety risks…safety risks…•• Overall ST and other safety outcomes Overall ST and other safety outcomes

(mortality, MI) have been similar for BMS (mortality, MI) have been similar for BMS and DESand DES

•• Continued longContinued long--term FU and investigation term FU and investigation of newer DES systems is neededof newer DES systems is needed

•• Issues of DAPT adherence are critical in the Issues of DAPT adherence are critical in the clinical settingclinical setting

Efficacy of DES vs. BMS in STEMI:Case Closed?

•• Because of lower absolute event rates Because of lower absolute event rates of TLR, careful attention to absolute of TLR, careful attention to absolute risk reductions (and number needed to risk reductions (and number needed to treat) rather than relative risk treat) rather than relative risk reductions is neededreductions is needed•• An estimation of baseline restenotic An estimation of baseline restenotic

risk should be performed in order to risk should be performed in order to determine the potential benefit of DES determine the potential benefit of DES in an individual patient!!in an individual patient!!