horizons 1year des

8/14/2019 Horizons 1Year DES

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A Prospective, Randomized Comparison ofA Prospective, Randomized Comparison of

Paclitaxel-eluting TAXUS Stents vs. BarePaclitaxel-eluting TAXUS Stents vs. Bare

Metal Stents During Primary Angioplasty inMetal Stents During Primary Angioplasty in

Acute Myocardial InfarctionAcute Myocardial Infarction

One Year Results One Year Results

Gregg W. Stone MDGregg W. Stone MDFor the HORIZONS-AMI InvestigatorsFor the HORIZONS-AMI Investigators


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Background

No consensus exists regarding the safety andNo consensus exists regarding the safety and

efficacy of drug-eluting stents in pts with STEMIefficacy of drug-eluting stents in pts with STEMIundergoing primary PCIundergoing primary PCI

TLR and restenosis rates tend to be lower inTLR and restenosis rates tend to be lower in

STEMI vs. elective PCI patients because of lessSTEMI vs. elective PCI patients because of lessplaque burden and non viable myocardiumplaque burden and non viable myocardium

The safety of implanting DES in ruptured plaquesThe safety of implanting DES in ruptured plaques

with thrombus has been questionedwith thrombus has been questioned

Outcomes from registry studies of DES vs. BMS inOutcomes from registry studies of DES vs. BMS in

STEMI have been conflicting, and no large-scaleSTEMI have been conflicting, and no large-scale

randomized trials have been performedrandomized trials have been performed


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HHarmonizingarmonizing OOutcomes withutcomes with RRevascularevascularizizatiationon andand SStents intents in AMIAMI

3602 pts with STEMI with symptom onset 12 hours3602 pts with STEMI with symptom onset 12 hours

Emergent angiography, followed by triage toEmergent angiography, followed by triage to

Primary PCIPrimary PCICABGCABG Medical RxMedical Rx

UFH + GP IIb/IIIa inhibitorUFH + GP IIb/IIIa inhibitor

(abciximab or eptifibatide)(abciximab or eptifibatide)

Bivalirudin monotherapyBivalirudin monotherapy

( provisional GP IIb/IIIa)( provisional GP IIb/IIIa)

Aspirin, thienopyridineAspirin, thienopyridineR

1:1

3000 pts eligible for stent randomization3000 pts eligible for stent randomization R

3:1

Bare metal EXPRESS stentBare metal EXPRESS stentPaclitaxel-eluting TAXUS stentPaclitaxel-eluting TAXUS stent

Clinical FU at 30 days, 6 months, 1 year, and thenyearly through 5 years; angio FU at 13 months


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Stent Randomization HypothesesStent Randomization Hypotheses

In patients with STEMI undergoing primary PCI,In patients with STEMI undergoing primary PCI,the use of paclitaxel-eluting TAXUS stents ratherthe use of paclitaxel-eluting TAXUS stents rather

than bare metal EXPRESS stents will be:than bare metal EXPRESS stents will be:

Efficacious, as evidenced by reduced rates ofEfficacious, as evidenced by reduced rates of

ischemia-driven target lesion revascularizationischemia-driven target lesion revascularization

at 1-year and angiographic binary restenosisat 1-year and angiographic binary restenosis

at 13 months; andat 13 months; and

Safe, with non-inferior rates of the compositeSafe, with non-inferior rates of the compositemeasure of death, reinfarction, stent thrombosismeasure of death, reinfarction, stent thrombosis

or stroke at 1-yearor stroke at 1-year


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Clinical Inclusion Criteria

STEMI >20 mins and


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Principal Clinical Exclusion CriteriaPrincipal Clinical Exclusion Criteria Contraindication to any of the study medications

Prior administration of thrombolytic therapy, bivalirudin,Prior administration of thrombolytic therapy, bivalirudin,GP IIb/IIIa inhibitors, LMWH or fondaparinux for the presentGP IIb/IIIa inhibitors, LMWH or fondaparinux for the present

admissionadmission (prior UFH allowed)(prior UFH allowed)

Current use of coumadin

History of bleeding diathesis or known coagulopathyHistory of bleeding diathesis or known coagulopathy(including HIT), or will refuse blood transfusions(including HIT), or will refuse blood transfusions

History of intracerebral mass, aneurysm, AVM, orHistory of intracerebral mass, aneurysm, AVM, or

hemorrhagic stroke; stroke or TIA within 6 months or anyhemorrhagic stroke; stroke or TIA within 6 months or any

permanent neurologic deficit; GI or GU bleed within 2permanent neurologic deficit; GI or GU bleed within 2

months, or major surgery within 6 weeks; recent or knownmonths, or major surgery within 6 weeks; recent or known

platelet count


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Angiographic Inclusion Criteria The presence of least 1 acute infarct arteryThe presence of least 1 acute infarct artery

target vessel* in which:target vessel* in which:

a) ALL significant lesions are eligible for stentinga) ALL significant lesions are eligible for stenting

with study stents, andwith study stents, and

b) ALL such lesions have a visually estimatedb) ALL such lesions have a visually estimatedreference diameter 2.25 mm and 4.0 mmreference diameter 2.25 mm and 4.0 mm

Expected ability to deliver the stent(s) to allExpected ability to deliver the stent(s) to all

culprit lesionsculprit lesions (absence of excessive proximal(absence of excessive proximal

tortuosity or severe calcification)tortuosity or severe calcification)

Expected ability to fully expand the stent(s) at allExpected ability to fully expand the stent(s) at all

culprit lesionsculprit lesions (absence of marked calcification)(absence of marked calcification)

*Arteries containing multiple lesions may be randomized if all lesions are study stent eligible; multiple*Arteries containing multiple lesions may be randomized if all lesions are study stent eligible; multiplevessels may be randomized if all lesions in each vessel are study stent eligiblevessels may be randomized if all lesions in each vessel are study stent eligible


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Angiographic Exclusion CriteriaAngiographic Exclusion Criteria

Bifurcation lesion definitely requiring implantationBifurcation lesion definitely requiring implantation

ofofstents in both the main vessel + side branchstents in both the main vessel + side branch

Infarct related artery is anInfarct related artery is an unprotected left mainunprotected left main

>100 mm>100 mm of study stent length anticipatedof study stent length anticipated

Infarction due toInfarction due to stent thrombosisstent thrombosis, or infarct lesion, or infarct lesion

at the site of a previously implanted stentat the site of a previously implanted stent

High likelihood ofHigh likelihood ofCABG within 30 daysCABG within 30 days anticipatedanticipated


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2 Primary Stent Endpoints (at 12 Months)2 Primary Stent Endpoints (at 12 Months)

1) Ischemia-driven TLR*1) Ischemia-driven TLR*

2) Composite Safety MACE =2) Composite Safety MACE = AllAllcause death, reinfarction, stent thrombosis (ARCcause death, reinfarction, stent thrombosis (ARC

definite or probable)**, or strokedefinite or probable)**, or stroke

andand

* Related to randomized stent lesions (whether study or non study* Related to randomized stent lesions (whether study or non study

stents were implanted);stents were implanted);

Major Secondary Endpoint (at 13 Months)Major Secondary Endpoint (at 13 Months)

Binary angiographic restenosisBinary angiographic restenosis

** In randomized stent lesions with** In randomized stent lesions with1 stent implanted (whether study or non study stents)1 stent implanted (whether study or non study stents)


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Statistical MethodologyStatistical Methodology

Second randomization stratificationSecond randomization stratification

i.i. Results from the first randomizationResults from the first randomization

ii.ii. Presence of medically treated diabetes mellitusPresence of medically treated diabetes mellitus

iii.iii. Presence of any lesion >26 mm in lengthPresence of any lesion >26 mm in length

(requiring overlapping stents by protocol)(requiring overlapping stents by protocol)

iv.iv. U.S. vs. non-U.S. siteU.S. vs. non-U.S. site

Primary analysis conducted in the ITT cohortPrimary analysis conducted in the ITT cohort

using Kaplan-Meier methodology, with theusing Kaplan-Meier methodology, with thegroups compared by log-rankgroups compared by log-rank

1-sided1-sided =0.025 for NI; 2-sided=0.025 for NI; 2-sided =0.05 for Sup=0.05 for Sup


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Power AnalysisPower Analysis

Assumed event ratesAssumed event rates

One YearOne Year TestTest EXPRESSEXPRESS TAXUSTAXUS PowerPower

Ischemic TLRIschemic TLR SuperioritySuperiority 9.0%9.0% 5.0%5.0% -- 95%95%

CompositeCompositeSafety MACESafety MACE

NoninferiorityNoninferiority 7.5%7.5% 7.5%7.5% 3.0%3.0% 80%80%

With 2,850 pts randomized 3:1*With 2,850 pts randomized 3:1*

Assumed event ratesAssumed event rates

13 Months13 Months TestTest EXPRESSEXPRESS TAXUSTAXUS PowerPower

RestenosisRestenosis SuperioritySuperiority 26.0%26.0% 15.6%15.6% -- 96%96%

With angiographic FU in 1,125 randomized pts (analyzable)With angiographic FU in 1,125 randomized pts (analyzable)

* Assumed 5% withdrew or lost to FU at 1 year 3000 randomized* Assumed 5% withdrew or lost to FU at 1 year 3000 randomized


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Study OrganizationStudy Organization

Sponsor:Sponsor: The Cardiovascular Research FoundationThe Cardiovascular Research Foundation

Grant Support:Grant Support: Boston Scientific CorporationBoston Scientific Corporation (unrestricted)(unrestricted)

The Medicines CompanyThe Medicines Company

Principal Investigator:Principal Investigator: Gregg W. Stone MDGregg W. Stone MD

Steering Committee:Steering Committee: Gregg W. Stone (Chair), Bruce R. Brodie, DavidGregg W. Stone (Chair), Bruce R. Brodie, David

A. Cox, Cindy L. Grines, Barry D. RutherfordA. Cox, Cindy L. Grines, Barry D. Rutherford

European SteeringEuropean Steering H Bonnier, A Colombo, Eulogio Garcia,H Bonnier, A Colombo, Eulogio Garcia,

Committee:Committee: E Grube, G Guagliumi, A Kastrati,E Grube, G Guagliumi, A Kastrati,

P Serruys, H SuryapranataP Serruys, H Suryapranata

Additional CountryAdditional Country Y Almagor, A Banning, J Belardi, D Dudek,Y Almagor, A Banning, J Belardi, D Dudek,

Leaders:Leaders: L Grinfeld, K Huber, D Nilsen, G Olivecrona,L Grinfeld, K Huber, D Nilsen, G Olivecrona,

L RasmussenL Rasmussen

PharmacologyPharmacology Deepak Bhatt, George Dangas, Fred Feit,Deepak Bhatt, George Dangas, Fred Feit,

Committee:Committee: Magnus OhmanMagnus Ohman


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Study OrganizationStudy Organization Data Management:Data Management: CRF, Roxana Mehran (Director),CRF, Roxana Mehran (Director),

Lynn Vandertie, Louise GamboneLynn Vandertie, Louise Gambone

(Ops), Allison Kellock (Programming),(Ops), Allison Kellock (Programming),

Helen Parise (Stats)Helen Parise (Stats)

Clinical Events Committee:Clinical Events Committee: CRF, S. Chiu Wong (Chair)CRF, S. Chiu Wong (Chair)

Site and Data Monitoring:Site and Data Monitoring: J. Tyson and Associates (USA),J. Tyson and Associates (USA),

Premier (Europe), Tango (S.A.)Premier (Europe), Tango (S.A.)

Angiographic Core Lab:Angiographic Core Lab: CRF, Alexandra Lansky (Director),CRF, Alexandra Lansky (Director),

Ecaterina Cristea (Ops)Ecaterina Cristea (Ops)

ECG Core Lab:ECG Core Lab: CRF, James Reiffel (Director)CRF, James Reiffel (Director)

IVUS Core lab:IVUS Core lab: CRF, Akiko Maehara (Director)CRF, Akiko Maehara (Director)

DSMB:DSMB: Bernhard Gersh (Chair), David Faxon,Bernhard Gersh (Chair), David Faxon,

Spencer King, Stuart Pocock, DavidSpencer King, Stuart Pocock, David

WilliamsWilliams


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The Cardiovascular ResearchThe Cardiovascular Research

Foundation (CRF) HORIZONS-AMI TeamFoundation (CRF) HORIZONS-AMI Team

Sponsored by CRFSponsored by CRF


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Horizons Enrollment - CentersHorizons Enrollment - Centers

USA (57)

(1) Spain(1) Spain

(6) UK(6) UK

(2) Norway(2) Norway

Poland (9)Poland (9)

Germany (16)Germany (16)

Austria (5)Austria (5)

(3) Netherlands(3) Netherlands

Italy (2)Italy (2)

Argentina (12)Argentina (12)

Israel (10)Israel (10)

3,602 pts randomized at 123 centers in 11 countries

between March 25th, 2005 and May 7th, 2007


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Top 20 Enrolling SitesTop 20 Enrolling Sites

1. B. Witzenbichler, Germany

2. G. Guagliumi, Italy

3. J. Peruga, Poland

4. B. Brodie, USA

5. R. Kornowski,Israel

6. F. Hartmann, Germany

7. M. Moeckel, Germany

8. A. Ochala, Poland

9. W. Ruzyllo, Poland

10. V. Guetta, Israel

11. H. Suryapranata, Netherlands

12. K. Huber, Austria

13. J. Wehrle, Germany

14. C. Metzger, USA

15. M. Desaga, Germany

16. K. Zmudka, Poland

17. J. Kochman, Poland

18. D. Nilsen, Norway

19. D. Dudek, Poland

20. A. Finkelstein, Israel


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TAXUS DES

N=2257

EXPRESS BMS

N=749RandomizedRandomized

1 year FU1 year FUN=2186

(96.9%)

N=715

(95.5%)

Withdrew Withdrew

Lost to FU Lost to FU

1818

5353

77

2727

R

3:1

HHarmonizingarmonizing OOutcomes withutcomes with RRevascularevascularizizatiationon andand SStents intents in AMIAMI

3006 pts eligible for stent rand.3006 pts eligible for stent rand.

Primary Medical Rx 193

Primary CABG 62

Deferred PCI 2

Index PCI, not eligible

- PTCA only 119

- Stented 220

UFH + GPI (n=1802)

Bivalirudin (n=1800)

R

1:13602 pts with STEMI3602 pts with STEMI

93.1% of all stentedpts were randomized


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Baseline Characteristics (i)Baseline Characteristics (i)

TAXUSTAXUS

(N=2257)(N=2257)

EXPRESSEXPRESS

(N=749)(N=749)

Age (years)Age (years) 59.9 [52.4, 69.4]59.9 [52.4, 69.4] 59.3 [51.8, 69.2]59.3 [51.8, 69.2]

MaleMale 77.0%77.0% 76.0%76.0%

DiabetesDiabetes 16.1%16.1% 15.2%15.2%HypertensionHypertension 51.2%51.2% 51.9%51.9%

HyperlipidemiaHyperlipidemia 42.2%42.2% 41.1%41.1%

Current smokingCurrent smoking 46.3%46.3% 51.9%51.9%

Prior MIPrior MI 9.1%9.1% 10.9%10.9%

Prior PCIPrior PCI 9.5%9.5% 7.7%7.7%

Prior CABGPrior CABG 2.2%2.2% 1.9%1.9%

*P=0.009*P=0.009

**


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Baseline Characteristics (ii)Baseline Characteristics (ii)

TAXUSTAXUS

(N=2257)(N=2257)

EXPRESSEXPRESS

(N=749)(N=749)

Weight (kg)Weight (kg) 80 [71, 90]80 [71, 90] 80 [71, 90]80 [71, 90]

Killip class 2-4Killip class 2-4 8.8%8.8% 8.0%8.0%

Anterior MIAnterior MI 42.2%42.2% 44.7%44.7%

LVEF (%), siteLVEF (%), site 50 [44, 59]50 [44, 59] 50 [43, 58]50 [43, 58]

Symptoms PCI, hrsSymptoms PCI, hrs 3.7 [2.7, 5.5]3.7 [2.7, 5.5] 3.8 [2.7, 5.8]3.8 [2.7, 5.8]

Femoral a. accessFemoral a. access 93.6%93.6% 92.9%92.9%

Venous accessVenous access 8.5%8.5% 8.0%8.0%

Closure deviceClosure device 30.1%30.1% 28.8%28.8%

Aspiration catheterAspiration catheter 11.4%11.4% 10.7%10.7%


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Study DrugsStudy DrugsTAXUSTAXUS

(N=2257)(N=2257)EXPRESSEXPRESS

(N=749)(N=749)

Aspirin at homeAspirin at home 22.7%22.7% 20.5%20.5%

Aspirin load pre PCIAspirin load pre PCI 97.0%97.0% 97.2%97.2%

Thienopyridine at homeThienopyridine at home 2.1%2.1% 2.5%2.5%

Thienopyridine loading doseThienopyridine loading dose 98.9%98.9% 98.3%98.3%

- clopidogrel 300 mg- clopidogrel 300 mg 34.2%34.2% 35.5%35.5%

- clopidogrel 600 mg- clopidogrel 600 mg 63.3%63.3% 61.3%61.3%

- clopidogrel other- clopidogrel other 1.2%1.2% 1.3%1.3%

- ticlopidine- ticlopidine 0.5%0.5% 0.3%0.3%

UFH pre randomizationUFH pre randomization 65.2%65.2% 65.8%65.8%

UFH as the procedural antithrombinUFH as the procedural antithrombin 49.8%49.8% 50.1%50.1%

Bivalirudin administeredBivalirudin administered 50.7%50.7% 50.9%50.9%

GP IIb/IIIa inhibitor administeredGP IIb/IIIa inhibitor administered 52.0%52.0% 51.5%51.5%


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Procedural Data (Site Reported)Procedural Data (Site Reported)TAXUSTAXUS

(N=2257, L=2495)(N=2257, L=2495)EXPRESSEXPRESS

(N=749, L=815)(N=749, L=815)

N lesions treatedN lesions treated 1.1 0.41.1 0.4 1.1 0.41.1 0.4

- 2 lesions treated- 2 lesions treated 11.1%11.1% 9.0%9.0%

- 2 vessels treated- 2 vessels treated 4.5%4.5% 3.1%3.1%

Direct stenting attemptedDirect stenting attempted 30.4%30.4% 33.7%33.7%

Stent target lesion:Stent target lesion:

LAD, LCX, RCA, LM, SVGLAD, LCX, RCA, LM, SVG40.1%, 14.6%,40.1%, 14.6%,

45.1%, 0.3%, 0.3%45.1%, 0.3%, 0.3%42.4%, 15.9%,42.4%, 15.9%,

41.3%, 0.4%, 0.4%41.3%, 0.4%, 0.4%

N stents implantedN stents implanted 1.5 0.91.5 0.9 1.4 0.71.4 0.7

Total stent length**Total stent length** 30.8 17.830.8 17.8 27.3 14.927.3 14.9

Max balloon dia. (mm)Max balloon dia. (mm) 3.00 [2.75, 3.50]3.00 [2.75, 3.50] 3.00 [2.90, 3.50]3.00 [2.90, 3.50]

Max pressure (atm.)Max pressure (atm.) 14.0 [12.0, 16.0]14.0 [12.0, 16.0] 14.0 [12.0, 16.0]14.0 [12.0, 16.0]

*P=0.002; **P


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Aspirin and Thienopyridine UseAspirin and Thienopyridine Use

Antiplateletagentuse

(%)

Antiplateletagentuse

(%)

Regular* aspirin use (%)Regular* aspirin use (%) Regular* thieno. use (%)Regular* thieno. use (%)

*Taken >50% of days since last visit*Taken >50% of days since last visit

99.1%

98.6%

98.5%

98.3% 97.5%

98.3%

97.1%

97.5%99.4%

98.9%

98.7%

97.8%

94.7%

87.5%

73.1%

63.9%P


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22572257 21322132 20982098 20692069 18681868

749749 697697 675675 658658 603603

Number at riskNumber at risk

TAXUS DESTAXUS DES

EXPRESS BMSEXPRESS BMS

Primary Efficacy Endpoint:Primary Efficacy Endpoint: Ischemic TLRIschemic TLR

Ischem

icTLR(%)

Ischem

icTLR(%)

00

11

22

33

44

55

66

77

88

99

1010

Time in MonthsTime in Months

00 11 22 33 44 55 66 77 88 99 1010 1111 1212

7.5%7.5%

4.5%4.5%

Diff [95%CI] =Diff [95%CI] =

-3.0% [-5.1, -0.9]-3.0% [-5.1, -0.9]

HR [95%CI] =HR [95%CI] =

0.59 [0.43, 0.83]0.59 [0.43, 0.83]

P=0.002P=0.002

TAXUS DES (n=2257)TAXUS DES (n=2257)

EXPRESS BMS (n=749)EXPRESS BMS (n=749)


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Ischem

icTVR(%)

0

1

2

3

4

5

6

7

89

10

Time in Months

0 1 2 3 4 5 6 7 8 9 10 11 12

22572257 21192119 20782078 20452045 18481848

749749 695695 669669 650650 598598


TAXUS DESTAXUS DES


8.7%

5.8%

Diff [95%CI] =

-3.0% [-5.2, -0.7]HR [95%CI] =

0.65 [0.48, 0.89]

P=0.006



Secondary Efficacy Endpoint:Secondary Efficacy Endpoint: Ischemic TVRIschemic TVR


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Primary Safety Endpoint:Primary Safety Endpoint: Safety MACE*Safety MACE*

Safety

MACE(%)

Safety

MACE(%)

00

11

22

33

44

55

66

77

8899

1010


00 11 22 33 44 55 66 77 88 99 1010 1111 1212

22572257 21152115 20862086 20572057 18561856

749749 697697 683683 672672 619619


TAXUS DESTAXUS DES




8.1%8.1%8.0%8.0%

Diff [95%CI] =Diff [95%CI] =

0.1% [-2.1, 2.4]0.1% [-2.1, 2.4]

HR [95%CI] =HR [95%CI] =1.02 [0.76, 1.36]1.02 [0.76, 1.36]

PPNINI=0.01=0.01

PPSupSup=0.92=0.92

* Safety MACE = death, reinfarction, stroke, or stent thrombosis* Safety MACE = death, reinfarction, stroke, or stent thrombosis


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One-Year All-Cause MortalityOne-Year All-Cause Mortality

Mortality(%)

0

1

2

3

4

5

Time in Months

0 1 2 3 4 5 6 7 8 9 10 11 12

22572257 21802180 21612161 21472147 19491949

749749 716716 712712 702702 648648


TAXUS DESTAXUS DES




3.5%3.5%

HR [95%CI] =0.99 [0.64,1.55]

P=0.98


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One-Year Cardiac MortalityOne-Year Cardiac Mortality

22572257 21802180 21612161 21472147 19491949

749749 716716 712712 702702 648648


TAXUS DESTAXUS DES


Cardiac

Mortality(%

)

Cardiac

Mortality(%

)

00

11

22

33

44

55


00 11 22 33 44 55 66 77 88 99 1010 1111 1212



2.7%2.4%

HR [95%CI] =

0.90 [0.54,1.50]

P=0.68


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One-Year Death or ReinfarctionOne-Year Death or Reinfarction

Death

orMI(%)

0

1

2

3

4

5

6

7

8

Time in Months

0 1 2 3 4 5 6 7 8 9 10 11 12

22572257 21402140 21102110 20832083 18821882

749749 703703 689689 678678 625625


TAXUS DESTAXUS DES




7.0%6.8%

HR [95%CI] =

0.97 [0.70,1.32]P=0.83


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Stent Thrombosis (ARC Definite or Probable)Stent Thrombosis (ARC Definite or Probable)

22382238 21222122 20982098 20782078 18841884

744744 701701 694694 683683 629629


TAXUS DESTAXUS DES


StentThrombosis(%

)

StentThrombosis(%

)

00

11

22

33

44


00 11 22 33 44 55 66 77 88 99 1010 1111 1212



3.4%3.1%

HR [95%CI] =

0.92 [0.58,1.45]

P=0.72


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Stent Thrombosis Rates*Stent Thrombosis Rates*

TAXUSTAXUS


(N=744)(N=744)Hazard ratioHazard ratio

[95%CI][95%CI]PP

ValueValue

Stent thrombosis, 30 daysStent thrombosis, 30 days 2.3%2.3% 2.7%2.7% 0.87 [0.52,1.46]0.87 [0.52,1.46] 0.600.60

- ARC definite- ARC definite 1.9%1.9% 2.3%2.3% 0.83 [0.47,1.45]0.83 [0.47,1.45] 0.510.51

- ARC probable- ARC probable 0.5%0.5% 0.4%0.4% 1.11 [0.31,4.05]1.11 [0.31,4.05] 0.870.87

Stent thrombosis, >30d 1yStent thrombosis, >30d 1y 1.0%1.0% 0.7%0.7% 1.39 [0.52,3.68]1.39 [0.52,3.68] 0.510.51


- ARC probable- ARC probable 0.1%0.1% 0%0% -- 0.420.42

Stent thrombosis, 1 yearStent thrombosis, 1 year 3.1%3.1% 3.4%3.4% 0.92 [0.58,1.45]0.92 [0.58,1.45] 0.720.72


- ARC probable- ARC probable 0.5%0.5% 0.4%0.4% 1.33 [0.38,4.73]1.33 [0.38,4.73] 0.650.65

*Kaplan-Meier estimates*Kaplan-Meier estimates


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One Year Composite Safety Endpoints*One Year Composite Safety Endpoints*

TAXUSTAXUS


(N=749)(N=749)HR [95%CI]HR [95%CI]

PP

ValueValue

Safety MACE**Safety MACE** 8.1%8.1% 8.0%8.0% 1.021.02 [0.76,1.36][0.76,1.36] 0.920.92

Death, all-causeDeath, all-cause 3.5%3.5% 3.5%3.5% 0.990.99 [0.64,1.55][0.64,1.55] 0.980.98

- Cardiac- Cardiac 2.4%2.4% 2.7%2.7% 0.900.90 [0.54,1.50][0.54,1.50] 0.680.68

- Non cardiac- Non cardiac 1.1%1.1% 0.8%0.8% 1.321.32 [0.54,3.22][0.54,3.22] 0.550.55

ReinfarctionReinfarction 3.7%3.7% 4.5%4.5% 0.810.81 [0.54,1.21][0.54,1.21] 0.310.31

- Q-wave- Q-wave 2.0%2.0% 1.9%1.9% 1.071.07 [0.59,1.94][0.59,1.94] 0.830.83

- Non Q-wave- Non Q-wave 1.8%1.8% 2.7%2.7% 0.680.68 [0.39,1.17][0.39,1.17] 0.160.16

Stent thrombosisStent thrombosis

3.1%3.1% 3.4%3.4% 0.920.92 [0.58,1.45][0.58,1.45] 0.720.72- ARC definite- ARC definite 2.6%2.6% 3.0%3.0% 0.860.86 [0.53,1.41][0.53,1.41] 0.550.55

- ARC probable- ARC probable 0.5%0.5% 0.4%0.4% 1.331.33 [0.38,4.73][0.38,4.73] 0.650.65

StrokeStroke 1.0%1.0% 0.7%0.7% 1.521.52 [0.58,4.00][0.58,4.00] 0.390.39

*Kaplan-Meier estimates; **Primary safety endpoint;*Kaplan-Meier estimates; **Primary safety endpoint; ARC definite or probableARC definite or probable


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Angiographic Follow-upAngiographic Follow-up

TAXUS DES

N=1348

EXPRESS BMS

N=452RandomizedRandomized

EligibleEligible N=1308 N=441

1800 consecutive eligible pts assigned to1800 consecutive eligible pts assigned to

13 month angiographic FU*13 month angiographic FU*

* Randomized in stent arm; stent procedure successful (DS


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Follow-up QCAFollow-up QCATAXUSTAXUS

(L=1081, V=964)(L=1081, V=964)EXPRESSEXPRESS

(L=332, V=302)(L=332, V=302)P valueP value

TIMI flowTIMI flow

- 0/1- 0/1 2.8%2.8% 3.6%3.6% 0.450.45

- 2- 2 7.0%7.0% 5.0%5.0% 0.220.22

- 3- 3 90.2%90.2% 91.4%91.4% 0.550.55

FU RVD (mm)FU RVD (mm) 2.91 0.492.91 0.49 2.90 0.482.90 0.48 0.970.97

FU MLD in-stent (mm)FU MLD in-stent (mm) 2.36 0.752.36 0.75 1.98 0.821.98 0.82


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Binary Analysis Segment Restenosis at 13 Months

Patient and Lesion Level Analysis*

RR [95%CI] =RR [95%CI] =

0.44 [0.33, 0.57]0.44 [0.33, 0.57]

P


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Angiographic Late Loss at 13 MonthLesions with Stents Implanted

P


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Binary Angiographic Restenosis at 13 MonthsLesions with Stents Implanted

RR [95%CI] =RR [95%CI] =

0.42 [0.32, 0.54]0.42 [0.32, 0.54]

P


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LimitationsLimitations

Open label designOpen label design

Potential bias was mitigated by high protocolPotential bias was mitigated by high protocol

procedure compliance and use of blindedprocedure compliance and use of blinded

clinical event adjudication committees andclinical event adjudication committees and

core laboratoriescore laboratories

Underpowered for stent thrombosis and deathUnderpowered for stent thrombosis and death

The virtually identical rates of MACE in theThe virtually identical rates of MACE in the

TAXUS and EXPRESS groups makes itTAXUS and EXPRESS groups makes itunlikely that major safety differences existunlikely that major safety differences exist

favoring either stent type at 1-yearfavoring either stent type at 1-year


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ConclusionsConclusions

In this large-scale, prospective, randomized trial ofIn this large-scale, prospective, randomized trial of

pts with STEMI undergoing primary stenting, thepts with STEMI undergoing primary stenting, theimplantation of paclitaxel-eluting TAXUS stentsimplantation of paclitaxel-eluting TAXUS stents

compared to bare metal EXPRESS stents resulted in:compared to bare metal EXPRESS stents resulted in:

A significant 41% reduction in the 1-year primaryA significant 41% reduction in the 1-year primaryefficacy endpoint of ischemia-driven TLR, and aefficacy endpoint of ischemia-driven TLR, and a

significant 56% reduction in the 13 month majorsignificant 56% reduction in the 13 month major

secondary efficacy endpoint of binary restenosissecondary efficacy endpoint of binary restenosis

Non inferior rates of the primary composite safetyNon inferior rates of the primary composite safety

endpoint of all cause death, reinfarction, stentendpoint of all cause death, reinfarction, stent

thrombosis or stroke at 1-yearthrombosis or stroke at 1-year


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ConclusionsConclusions

The long-term safety and efficacy profileThe long-term safety and efficacy profile

of paclitaxel-eluting TAXUS stentsof paclitaxel-eluting TAXUS stents

compared to bare metal EXPRESS stentscompared to bare metal EXPRESS stents

in STEMI will be determined by thein STEMI will be determined by the

ongoing 5 year follow-up of patientsongoing 5 year follow-up of patientsrandomized in the HORIZONS-AMI trialrandomized in the HORIZONS-AMI trial

horizons 1year des

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