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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
Number at riskNumber at risk
TAXUS DESTAXUS DES
EXPRESS BMSEXPRESS BMS
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
TAXUS DES (n=2257)TAXUS DES (n=2257)
EXPRESS BMS (n=749)EXPRESS BMS (n=749)
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
Time in MonthsTime in Months
00 11 22 33 44 55 66 77 88 99 1010 1111 1212
22572257 21152115 20862086 20572057 18561856
749749 697697 683683 672672 619619
Number at riskNumber at risk
TAXUS DESTAXUS DES
EXPRESS BMSEXPRESS BMS
TAXUS DES (n=2257)TAXUS DES (n=2257)
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
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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
Number at riskNumber at risk
TAXUS DESTAXUS DES
EXPRESS BMSEXPRESS BMS
TAXUS DES (n=2257)TAXUS DES (n=2257)
EXPRESS BMS (n=749)EXPRESS BMS (n=749)
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
Number at riskNumber at risk
TAXUS DESTAXUS DES
EXPRESS BMSEXPRESS BMS
Cardiac
Mortality(%
)
Cardiac
Mortality(%
)
00
11
22
33
44
55
Time in MonthsTime in Months
00 11 22 33 44 55 66 77 88 99 1010 1111 1212
TAXUS DES (n=2257)TAXUS DES (n=2257)
EXPRESS BMS (n=749)EXPRESS BMS (n=749)
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
Number at riskNumber at risk
TAXUS DESTAXUS DES
EXPRESS BMSEXPRESS BMS
TAXUS DES (n=2257)TAXUS DES (n=2257)
EXPRESS BMS (n=749)EXPRESS BMS (n=749)
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
Number at riskNumber at risk
TAXUS DESTAXUS DES
EXPRESS BMSEXPRESS BMS
StentThrombosis(%
)
StentThrombosis(%
)
00
11
22
33
44
Time in MonthsTime in Months
00 11 22 33 44 55 66 77 88 99 1010 1111 1212
TAXUS DES (n=2238)TAXUS DES (n=2238)
EXPRESS BMS (n=744)EXPRESS BMS (n=744)
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=2238)(N=2238)EXPRESSEXPRESS
(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 definite- ARC definite 0.9%0.9% 0.7%0.7% 1.25 [0.47,3.35]1.25 [0.47,3.35] 0.650.65
- 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 definite- ARC definite 2.6%2.6% 3.0%3.0% 0.86 [0.53,1.41]0.86 [0.53,1.41] 0.550.55
- 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=2257)(N=2257)EXPRESSEXPRESS
(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