Download - A Prospective, Randomized Comparison of Paclitaxel-eluting TAXUS Stents vs. Bare Metal Stents During Primary Angioplasty in Acute Myocardial Infarction.

A Prospective, Randomized Comparison of A Prospective, Randomized Comparison of Paclitaxel-eluting TAXUS Stents vs. Bare Paclitaxel-eluting TAXUS Stents vs. Bare

Metal Stents During Primary Angioplasty in Metal 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

A Prospective, Randomized Comparison of A Prospective, Randomized Comparison of Paclitaxel-eluting TAXUS Stents vs. Bare Paclitaxel-eluting TAXUS Stents vs. Bare

Metal Stents During Primary Angioplasty in Metal 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

Background No consensus exists regarding the safety and efficacy of drug-No consensus exists regarding the safety and efficacy of drug-

eluting stents in pts with STEMI undergoing primary PCIeluting stents in pts with STEMI undergoing primary PCI

– TLR and restenosis rates tend to be lower in STEMI vs. TLR and restenosis rates tend to be lower in STEMI vs. elective PCI patients because of less plaque burden and non elective PCI patients because of less plaque burden and non viable myocardiumviable myocardium

– The safety of implanting DES in ruptured plaques with The safety of implanting DES in ruptured plaques with thrombus has been questionedthrombus has been questioned

Outcomes from registry studies of DES vs. BMS in STEMI have Outcomes from registry studies of DES vs. BMS in STEMI have been conflicting, and no large-scale randomized trials have been conflicting, and no large-scale randomized trials have been performedbeen performed

HHarmonizing armonizing OOutcomes with utcomes with RRevascularevascularizizatiationon and and SStents in tents in AMIAMI

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

Emergent angiography, followed by triage to…Emergent 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, thienopyridine R 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

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

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 rather the 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 of Efficacious, as evidenced by reduced rates of ischemia-driven target lesion revascularization ischemia-driven target lesion revascularization at 1-year and angiographic binary restenosis at 1-year and angiographic binary restenosis at 13 months; and at 13 months; and

– Safe, with non-inferior rates of the composite Safe, with non-inferior rates of the composite measure of death, reinfarction, stent thrombosis measure of death, reinfarction, stent thrombosis or stroke at 1-yearor stroke at 1-year

Clinical Inclusion Criteria STEMI >20 mins and <12 hours in duration

– ST-segment elevation of 1 mm in 2 contiguous leads; or

– Presumably new left bundle branch block; or

– True posterior MI with ST depression of 1 mm in 2 contiguous anterior leads

– Patients with cardiogenic shock, left main disease, etc., were not excluded

Age ≥18 years

Written, informed consent

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

Prior administration of thrombolytic therapy, bivalirudin, GP IIb/IIIa Prior administration of thrombolytic therapy, bivalirudin, GP IIb/IIIa inhibitors, LMWH or fondaparinux for the present admission inhibitors, LMWH or fondaparinux for the present admission (prior UFH (prior UFH allowed)allowed)

Current use of coumadin

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

History of intracerebral mass, aneurysm, AVM, or hemorrhagic stroke; History of intracerebral mass, aneurysm, AVM, or hemorrhagic stroke; stroke or TIA within 6 months or any permanent neurologic deficit; GI or stroke or TIA within 6 months or any permanent neurologic deficit; GI or GU bleed within 2 months, or major surgery within 6 weeks; recent or GU bleed within 2 months, or major surgery within 6 weeks; recent or known platelet count <100,000 cells/mmknown platelet count <100,000 cells/mm33 or hgb <10 g/dL or hgb <10 g/dL

Planned elective surgical procedure that would necessitate interruption of Planned elective surgical procedure that would necessitate interruption of thienopyridines during the first 6 months post enrollment thienopyridines during the first 6 months post enrollment

Angiographic Inclusion Criteria The presence of least 1 acute infarct artery target vessel* in The presence of least 1 acute infarct artery target vessel* in

which:which:

– a) ALL significant lesions are eligible for stenting a) ALL significant lesions are eligible for stenting with study with study stents, andstents, and

– b) ALL such lesions have a visually estimated b) ALL such lesions have a visually estimated reference reference diameter ≥2.25 mm and ≤4.0 mmdiameter ≥2.25 mm and ≤4.0 mm

Expected ability to deliver the stent(s) to all culprit lesions Expected ability to deliver the stent(s) to all culprit lesions (absence of excessive proximal tortuosity or severe (absence of excessive proximal tortuosity or severe calcification)calcification)

Expected ability to fully expand the stent(s) at all culprit Expected ability to fully expand the stent(s) at all culprit lesions lesions (absence of marked calcification)(absence of marked calcification)

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

Angiographic Exclusion CriteriaAngiographic Exclusion Criteria

Bifurcation lesion definitely requiring implantation of Bifurcation lesion definitely requiring implantation of stents stents in both the main vessel + side branchin both the main vessel + side branch

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

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

Infarction due to Infarction due to stent thrombosisstent thrombosis, or infarct lesion at the site , or infarct lesion at the site of a previously implanted stentof a previously implanted stent

High likelihood of High likelihood of CABG within 30 days CABG within 30 days anticipatedanticipated

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 = All cause death, reinfarction, stent thrombosis All cause death, reinfarction, stent thrombosis

(ARC definite or probable)**, or stroke (ARC definite or probable)**, or stroke

andand

* Related to randomized stent lesions (whether study or non * Related to randomized stent lesions (whether study or non study stents were implanted); study stents were implanted);

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

Binary angiographic restenosisBinary angiographic restenosis

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

Statistical MethodologyStatistical Methodology Second randomization stratification Second randomization stratification

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

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

iii.iii. Presence of any lesion >26 mm in length Presence 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 cohort Primary analysis conducted in the ITT cohort using Kaplan-Meier methodology, with the using Kaplan-Meier methodology, with the groups compared by log-rankgroups compared by log-rank

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

Power AnalysisPower Analysis

Assumed event ratesAssumed event rates

One YearOne Year TestTest EXPRESS EXPRESS TAXUSTAXUS PowerPower

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

Composite Composite Safety 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 EXPRESS EXPRESS 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

Study OrganizationStudy Organization Sponsor:Sponsor: The Cardiovascular Research FoundationThe Cardiovascular Research Foundation

Grant Support:Grant Support: Boston Scientific Corporation Boston 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, David Gregg 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

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

Lynn Vandertie, Louise Gambone Lynn Vandertie, Louise Gambone (Ops), Allison Kellock (Ops), Allison Kellock

(Programming), (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 Bernhard Gersh (Chair), David Faxon, Faxon, Spencer King, Stuart Pocock, David Spencer King, Stuart Pocock, David

WilliamsWilliams

The Cardiovascular Research The Cardiovascular Research Foundation (CRF) HORIZONS-AMI TeamFoundation (CRF) HORIZONS-AMI Team

Sponsored by CRFSponsored by CRF

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

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. Wöehrle, 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

TAXUS DESN=2257

EXPRESS BMSN=749RandomizedRandomized

1 year FU1 year FUN=2186(96.9%)

N=715(95.5%)

• • • • • • Withdrew • • •Withdrew • • •

• • • • • • Lost to FU • • •Lost to FU • • •1818

535377

2727

R 3:1

HHarmonizing armonizing OOutcomes with utcomes with RRevascularevascularizizatiationon and and SStents in tents in AMIAMI

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

Primary Medical Rx 193Primary CABG 62Deferred PCI 2Index 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 stented pts were randomized

Baseline Characteristics (i)Baseline Characteristics (i)TAXUSTAXUS

(N=2257)(N=2257)EXPRESSEXPRESS(N=749)(N=749)

Age (years)Age (years) 59.9 [52.4, 59.9 [52.4, 69.4]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

**

Baseline Characteristics (ii)Baseline Characteristics (ii)TAXUSTAXUS


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%

Study DrugsStudy DrugsTAXUSTAXUS


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%

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, SVG

40.1%, 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<0.0001*P=0.002; **P<0.0001

******

Quantitative Coronary AngiographyQuantitative Coronary AngiographyTAXUSTAXUS

(L=2642, V=2353)(L=2642, V=2353)EXPRESSEXPRESS

(L=857, V=771)(L=857, V=771)

Pre RVD (mm)Pre RVD (mm) 2.89 ± 0.512.89 ± 0.51 2.90 ± 0.502.90 ± 0.50

Pre MLD (mm)Pre MLD (mm) 0.35 ± 0.450.35 ± 0.45 0.35 ± 0.450.35 ± 0.45

Pre %DSPre %DS 87.6 ± 15.487.6 ± 15.4 87.4 ± 15.487.4 ± 15.4

Pre lesion length (mm)Pre lesion length (mm) 17.5 ± 10.117.5 ± 10.1 16.2 ± 8.816.2 ± 8.8

Pre TIMI 0/1, 2, 3Pre TIMI 0/1, 2, 3 60.6%, 13.6%, 25.7%60.6%, 13.6%, 25.7% 57.4%, 15.2%, 27.4% 57.4%, 15.2%, 27.4%

Post RVD (mm)Post RVD (mm) 2.93 ± 0.512.93 ± 0.51 2.95 ± 0.502.95 ± 0.50

Post MLD (mm)*Post MLD (mm)* 2.36 ± 0.552.36 ± 0.55 2.37 ± 0.522.37 ± 0.52

Post %DS*Post %DS* 19.9 ± 11.619.9 ± 11.6 19.5 ± 11.119.5 ± 11.1

Acute gain (mm)**Acute gain (mm)** 2.04 ± 0.642.04 ± 0.64 2.05 ± 0.622.05 ± 0.62

Post TIMI 0/1, 2, 3Post TIMI 0/1, 2, 3 1.7%, 10.7%, 87.6%1.7%, 10.7%, 87.6% 0.9%, 9.3%, 89.8% 0.9%, 9.3%, 89.8%

*Analysis segment, all lesions, whether stented or not; **stented lesions only; *Analysis segment, all lesions, whether stented or not; **stented lesions only; ††P=0.006P=0.006

††

Aspirin and Thienopyridine UseAspirin and Thienopyridine UseA

nti

pla

tele

t ag

ent

use

(%

)A

nti

pla

tele

t ag

ent

use

(%

)

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<0.001P<0.001

P<0.001P<0.001

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

TL

R (

%)

Isch

emic

TL

R (

%)

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)

Isch

emic

TV

R (

%)

0

1

2

3

4

5

6

7

8

9

10

Time in Months

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

22572257 21192119 20782078 20452045 18481848749749 695695 669669 650650 598598


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

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

Saf

ety

MA

CE

(%

)S

afet

y M

AC

E (

%)

00

11

22

33

44

55

66

77

88

99

1010


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

22572257 21152115 20862086 20572057 18561856749749 697697 683683 672672 619619



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

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

Mo

rtal

ity

(%)

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 19491949749749 716716 712712 702702 648648




3.5%3.5%

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

P=0.98

One-Year Death or ReinfarctionOne-Year Death or Reinfarction

Dea

th o

r M

I (%

)

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 18821882749749 703703 689689 678678 625625



EXPRESS BMS (n=749)EXPRESS BMS (n=749) 7.0%6.8%

HR [95%CI] =0.97 [0.70,1.32]

P=0.83

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

22382238 21222122 20982098 20782078 18841884744744 701701 694694 683683 629629


Ste

nt

Th

rom

bo

sis

(%)

Ste

nt

Th

rom

bo

sis

(%)

00

11

22

33

44


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


EXPRESS BMS (n=744)EXPRESS BMS (n=744) 3.4%3.1%

HR [95%CI] =0.92 [0.58,1.45]

P=0.72

Stent Thrombosis Rates*Stent Thrombosis Rates*TAXUSTAXUS


Hazard ratioHazard ratio[95%CI][95%CI]

P P 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

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

(N=2257)(N=2257)EXPRESSEXPRESS(N=749)(N=749) HR [95%CI]HR [95%CI] P P

ValueValue

Safety MACE**Safety MACE** 8.1%8.1% 8.0%8.0% 1.02 1.02 [0.76,1.36][0.76,1.36] 0.920.92

Death, all-causeDeath, all-cause 3.5%3.5% 3.5%3.5% 0.99 0.99 [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% 0.81 0.81 [0.54,1.21][0.54,1.21] 0.310.31

- Q-wave- Q-wave 2.0%2.0% 1.9%1.9% 1.07 1.07 [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% 0.68 0.68 [0.39,1.17][0.39,1.17] 0.160.16

Stent thrombosisStent thrombosis†† 3.1%3.1% 3.4%3.4% 0.92 0.92 [0.58,1.45][0.58,1.45] 0.720.72

- ARC definite- ARC definite 2.6%2.6% 3.0%3.0% 0.86 0.86 [0.53,1.41][0.53,1.41] 0.550.55

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

StrokeStroke 1.0%1.0% 0.7%0.7% 1.52 1.52 [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

Angiographic Follow-upAngiographic Follow-up

TAXUS DESN=1348

EXPRESS BMSN=452

RandomizedRandomized

EligibleEligible N=1308 N=441

1800 consecutive eligible pts assigned 1800 consecutive eligible pts assigned to 13 month angiographic FU*to 13 month angiographic FU*

* Randomized in stent arm; stent procedure successful (DS <10%, TIMI-3 flow, * Randomized in stent arm; stent procedure successful (DS <10%, TIMI-3 flow, ≤NHLBI type A peri-stent dissection); no stent thrombosis or CABG w/i 30 ≤NHLBI type A peri-stent dissection); no stent thrombosis or CABG w/i 30 daysdays

4040 1111• • • • • • Died before angio FU • • • Died before angio FU • • •

N=942(72.0%)

N=307(69.6%)

CompletedCompletedAngio FUAngio FU

366366 134134 • • Angio FU not performed • Angio FU not performed •

• • • • Not received/analyzable • •Not received/analyzable • •

• • • • • • • • Out of window • • • •Out of window • • • •2828

331414

00

N=911 N=293AnalyzedAnalyzed • • • • • • Lesions • • • Lesions • • • 10811081 332332

Follow-up QCAFollow-up QCATAXUSTAXUS

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

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

valuevalue

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 <0.0001<0.0001

FU MLD in-segment (mm)FU MLD in-segment (mm) 2.08 ± 0.692.08 ± 0.69 1.84 ± 0.761.84 ± 0.76 <0.0001<0.0001

FU %DS in-stentFU %DS in-stent 18.8 ± 22.918.8 ± 22.9 32.6 ± 24.932.6 ± 24.9 <0.0001<0.0001

FU %DS in-segmentFU %DS in-segment 28.8 ± 19.628.8 ± 19.6 37.4 ± 22.037.4 ± 22.0 <0.0001<0.0001

AneurysmAneurysm 0.5%0.5% 0.9%0.9% 0.400.40

UlceratedUlcerated 0.5%0.5% 0.6%0.6% 0.670.67

EctasiaEctasia 0.7%0.7% 0.9%0.9% 0.730.73

Binary Analysis Segment Restenosis at 13 MonthsPatient and Lesion Level Analysis*

RR [95%CI] = RR [95%CI] = 0.44 [0.33, 0.57]0.44 [0.33, 0.57]

P<0.0001P<0.0001

* ITT: Includes all stent randomized lesions, whether or not a stent * ITT: Includes all stent randomized lesions, whether or not a stent was implanted, and whether or not non study stents were placedwas implanted, and whether or not non study stents were placed

** Any lesion with restenosis ** Any lesion with restenosis per pt restenosis per pt restenosis

RR [95%CI] = RR [95%CI] = 0.44 [0.33, 0.57]0.44 [0.33, 0.57]

P<0.0001P<0.0001

Major 2 endpoint

Angiographic Late Loss at 13 Month Lesions with Stents Implanted

P<0.0001P<0.0001

P<0.0001P<0.0001

± 0.42

± 0.54

± 0.64

± 0.70

P = 0.18P = 0.18

P = 0.07P = 0.07

± 0.56

± 0.64

± 0.47

± 0.50

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<0.0001P<0.0001

RR [95%CI] = RR [95%CI] = 0.39 [0.29, 0.52]0.39 [0.29, 0.52]

P<0.0001P<0.0001

P = 0.13P = 0.13P = 0.42P = 0.42

LimitationsLimitations

Open label designOpen label design

– Potential bias was mitigated by high protocol Potential bias was mitigated by high protocol procedure compliance and use of blinded procedure compliance and use of blinded clinical event adjudication committees and clinical 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 the The virtually identical rates of MACE in the TAXUS and EXPRESS groups makes it TAXUS and EXPRESS groups makes it unlikely that major safety differences exist unlikely that major safety differences exist favoring either stent type at 1-year favoring either stent type at 1-year

ConclusionsConclusions In this large-scale, prospective, randomized trial of pts In this large-scale, prospective, randomized trial of pts

with STEMI undergoing primary stenting, the with STEMI undergoing primary stenting, the

implantation of paclitaxel-eluting TAXUS stents implantation 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 primary A significant 41% reduction in the 1-year primary

efficacy endpoint of ischemia-driven TLR, and a efficacy endpoint of ischemia-driven TLR, and a

significant 56% reduction in the 13 month major significant 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 safety Non inferior rates of the primary composite safety

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

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

ConclusionsConclusions

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

of paclitaxel-eluting TAXUS stents of paclitaxel-eluting TAXUS stents

compared to bare metal EXPRESS stents compared to bare metal EXPRESS stents

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

ongoing 5 year follow-up of patients ongoing 5 year follow-up of patients

randomized in the HORIZONS-AMI trialrandomized in the HORIZONS-AMI trial