PROMUSTM Stent

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SYNTAX - Top 30 Enrolling Centers I
Austria
Czech Rep
Norway
France
Germany
Hungary
Italy
2
SYNTAX - Top 30 Enrolling Centers II
Italy
Latvia
Netherlands
Poland
Sweden
UK
US
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SYNTAX

• Heart team meeting
• - surgeon(s) and interventional cardiologist(s)
  assess each patient
• Operative risk
• (EuroSCORE Parsonnet score)
• Coronary lesion complexity (SYNTAX score)

Dominance
BARI classification of coronary segments Leaman
score, Circ 198163285-299 Lesions
classification ACC/AHA , Circ 20011033019-3041
Bifurcation classification, CCI
200049274-283 CTO classification, J Am Coll
Cardiol 199730649-656
Sianos et al, EuroIntervention 20051219-227 Valg
imigli et al, Am J Cardiol 2007991072-1081 Serru
ys et al, EuroIntervention 20073450-459
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SYNTAX Trial- Eligible Patients
De novo disease

• Limited Exclusion Criteria
• Previous interventions (PCI or CABG)
• Acute MI with CPKgt2x
• Concomitant cardiac surgery

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SYNTAX Trial Design

23 US Sites
62 EU Sites
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SYNTAX Trial Design

23 US Sites
62 EU Sites
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SYNTAX Trial Design

23 US Sites
62 EU Sites
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Randomised Patient Flow (ITT)
Total randomized N1800
CABG 897 (49.8)
TAXUS903 (50.2)
Withdrawn 47 Lost to FU 13
7 5
40 8
12 mo Follow upN1740 (96.7)
TAXUS891 (98.7)
CABG849 (94.6)
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Patient Characteristics (l)Randomised Cohort
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Patient Characteristics (lI)Randomised Cohort
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Baseline Characteristics in DES PatientsSYNTAX
Trial Versus 2 Large, Multicenter MVD Registries
Creatinine gt220µmol/liter for NY State,
gt200µmol/liter for the SYNTAX trial
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Procedural CharacteristicsPCI Randomised Cohort
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Procedural CharacteristicsCABG Randomised Cohort
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Procedural CharacteristicsRandomised Cohort

Per protocol Complete revascularisation is
defined as the treatment of any lesion with
more than 50 diameter stenosis in vessels ? 1.5
mm diameter as estimated on the diagnostic
angiogram during the local Heart Team
conference. Completeness of revascularization
was assessed post procedure by the operator
(Surgeon or Interventional Cardiologist)
Allocation to procedure For PCI patients,
includes time for staged procedure
15
SYNTAX - All-cause mortality to 12 Months
P0.37
4.3
3.5
ITT Fisher Exact Test
16
SYNTAX - Cerebrovascular Events to 12 Months
P0.003
2.2
0.6
ITT Fisher Exact Test
17
SYNTAX - Myocardial Infarction to 12 Months
P0.11
4.8
3.2
ITT Fisher Exact Test
18
SYNTAX - Death/CVA/MI to 12 Months
P0.98
7.6
7.7
ITT Fisher Exact Test
19
SYNTAX - Symptomatic Graft Occlusion Stent
Thrombosis at 12 Months
TAXUS (N903)
CABG (N897)
P0.89
Patients ()
3.3
3.4
n27
n28
CABG
TAXUS
ITT population
20
SYNTAX - Repeat Revascularisation to 12 Months
Plt0.0001
13.7
5.9
ITT Fisher Exact Test
21
SYNTAX - MACCE to 12 Months
P0.0015
17.8
12.1
ITT Fisher Exact Test
22
SYNTAX - 12 Month Clinical Event Rates
CABG (N897)
TAXUS (N903)
All Death
P0.37
3.5
4.3
CVA
P0.003
2.2
0.6
MI
P0.11
3.2
4.8
Death/MI/CVA
P0.98
7.7
7.6
Revascularisation
Plt0.0001
5.9
13.7
Patients ()
ITT, Kaplan-Meier Rates Fisher Exact Test
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Primary Endpoint 12 Month MACCE
Non-inferiority analysis
Pre-specified Margin 6.6
95 CI 8.3
5.5
0
5
10
15
20
Difference in MACCE
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Stent Number and Length Higher in the SYNTAX Trial
Multivessel disease 96.2
3-vessel disease 90.8 Avg. stents per
patient 4.6 2.3 Avg. stented length 86.1
mm
Patients ()
Total Number of Stents Implanted per Patient
3VDLM/3VDLM/2VDLM/1VD
25
Average Number of Stents Implanted per Patient
SYNTAX Trial
Average number of stents implanted in SYNTAX is
higher than any other contemporary DES versus
CABG study
4.62.3
SYNTAX
26
Average Total Stented Length
SYNTAX Trial
86.147.9
Average total stent length (mm)
SYNTAX
27
Linear Increase in MACCE by Number of Stentsin
the SYNTAX Trial
12m MACCE in TAXUS Arm
1
2
3
4
5
6
7
8
Number of Stents Implanted
28
(No Transcript)
29
SYNTAX - Outcome according to Diabetic Status
P0.96
P0.0025
P0.08
P0.97
Death/CVA/MI
MACCE
MACCE
Death/CVA/MI
Non-Diabetic N1348
Diabetes (Medical Treatment) N452
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SYNTAX - Left Main Subgroup MACCE Rates at 12
Months
Patients ()
All LMN705
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SYNTAX - Left Main and Three Vessel Disease
Subgroup MACCE Rates at 12 Months
CABG
TAXUS
Patients ()
All LMN705
LM1VDN138
LM2VDN218
LM3VD N258
3VD ( w/o LM) N1095
LM IsolatedN91
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Contemporary studies of DES versus CABG1-Year
Mortality in CABG Arm
Multivessel
Left Main
Patients ()
Multivessel and/or Left Main
SYNTAX Trial (n897)
Yang2008(n390)
ARTS I(n602)
Lee, 2007(n103)
Javaid 2008(n505)
Sanmartin 2007(n245)
Palmerini 2006(n154)
Lee 2006(n123)
Chieffo 2006(n142)
33
Contemporary studies of DES versus CABG1-Year
TVR (PCI or CABG) in CABG Arm
Multivessel
Left Main
Multivessel and/or Left Main
Patients ()
SYNTAX Trial (n897)
Lee 2007(n103)
Sanmartin 2007(n245)
Palmerini 2006(n154)
Lee 2006(n123)
Chieffo 2006(n142)
ARTS I(n602)
Yang2008(n390)
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Contemporary studies of DES versus CABG1-Year
Stroke Rates in CABG Arm
Multivessel
Left Main
Multivessel and/or Left Main
Patients ()
SYNTAX Trial (n897)
Lee 2007(n103)
Javaid 2008(n505)
Sanmartin 2007(n245)
Chieffo 2006(n142)
ARTS I(n602)
Yang2008(n390)
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Contemporary studies of DES versus CABG1-Year
MAC(C)E Rates in CABG Arm
definitions vary across studies
Multivessel
Left Main
Multivessel and/or Left Main
Patients ()
SYNTAX Trial (n897)
Lee2007(n103)
Javaid 2008(n505)
Sanmartin 2007(n245)
Lee 2006(n123)
ARTS I(n602)
Yang2008(n390)
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Average Stent Number and Length in ARRIVE
Registry(N7,492 patients)
Multivessel disease 36.9
3-vessel stenting 1.2 Avg. stents per
patient 1.6 0.9 Avg. stented length 18.6
mm
Patients ()
Total Number of Stents Implanted per Patient
37
Average Stent Number and Length in OLYMPIA
Registry(N22,345 patients)
Multivessel disease 56.5
3-vessel stenting 1.3 Avg. stents per
patient 1.5 0.8 Avg. stented length 29.9
mm
Patients ()
Total Number of Stents Implanted per Patient
38
Stent Number and Length Higher in the SYNTAX Trial
Multivessel disease 96.2
3-vessel disease 90.8 Avg. stents per
patient 4.6 2.3 Avg. stented length 86.1
mm
Patients ()
Total Number of Stents Implanted per Patient
3VDLM/3VDLM/2VDLM/1VD
39
Average Number of Stents Implanted per Patient
SYNTAX Trial
Average number of stents implanted in SYNTAX is
higher than any other contemporary DES versus
CABG study
4.62.3
SYNTAX
40
Average Total Stented Length
SYNTAX Trial
86.147.9
Average total stent length (mm)
SYNTAX
41
Linear Increase in MACCE by Number of Stentsin
the SYNTAX Trial
12m MACCE in TAXUS Arm
1
2
3
4
5
6
7
8
Number of Stents Implanted
42
1-Year Mortality and Revascularisation Ratesin
TAXUS Stent Studies
Mortality
Revascularisation
Any Repeat Revascularization
Patients ()
Target vessel only
TAXUS SR Meta
ARRIVESimpleUse
ARRIVEMVStenting
SYNTAX Trial
TAXUS SR Meta
ARRIVESimpleUse
ARRIVEMVStenting
SYNTAX Trial
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Contemporary studies of DES versus CABG1-Year
Revascularisation in DES Arm
Multivessel
Left Main
Multivessel and/or Left Main
All Revasc.
Patients ()
35LM
All Revascularization
423VD
913VD
543VD
253VD
(TVR)
(TVR)
(TLR)
(TVR)
(All)
SYNTAX Trial (n903)
Yang2008(n441)
ARTS II(n607)
Hannan2008(n9963)
DELFT 2008(n358)
Sanmartin 2007(n96)
Palmerini 2006(n157)
Lee 2006(n50)
Chieffo 2006(n107)
44
Contemporary studies of DES versus CABG1-Year
Mortality in DES Arm
Multivessel
Left Main
Multivessel and/or Left Main
Patients ()
(cardiac)
Yang2008(n441)
ARTS II(n607)
Lee, 2007(n102)
Hannan 2008(n9963)
Javaid 2008(n95)
DELFT 2008(n358)
Sanmartin 2007(n96)
Palmerini 2006(n157)
Lee 2006(n50)
Chieffo 2006(n107)
SYNTAX Trial (n903)
45
Contemporary studies of DES versus CABG1-Year
Stroke Rates in DES Arm
Multivessel
Left Main
Patients ()
Multivessel and/or Left Main
Yang2008(n441)
ARTS II(n607)
Lee 2007(n102)
Javaid 2008(n95)
Sanmartin 2007(n96)
Chieffo 2006(n107)
SYNTAX Trial (n903)
46
Contemporary studies of DES versus CABG1-Year
MAC(C)E Rates in DES Arm
definitions vary across studies
Multivessel
Left Main
Patients ()
3VD
LM
Yang2008(n441)
ARTS II(n607)
Lee2007(n102)
Javaid 2008(n95)
DELFT 2008(n358)
Sanmartin 2007(n96)
Lee 2006(n50)
SYNTAX Trial
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Atherosclerosis A progressive process
PHASE I Initiation PHASE II
Progression PHASE III Complication
Disease progression
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Atherosclerotic progressionGlagovs remodeling
hypothesis
Progression
Normal vessel
Glagov S, et al. N Engl J Med. 19873161371-1375.
49
What types of lesions cause MI?
Coronary stenosis severity prior to MI
100
100
14
80
80
18
60
68
60
Coronary stenosis ()
40
40
20
20
0
0
All 4studies
Ambrose1988
Little1988
Nobuyoshi1991
Giroud1992
50-70
lt50
gt70
Falk E, et al. Circulation. 199592657-671.
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Atherosclerosis The first sign of CHD is often
sudden death or MI
Men
62 (552/895 men)
Women
45 (305/674 women)
0
20
30
40
50
60
70
10
Patients who experienced an MI ()
Murabito JM, et al. Circulation.
1993882548-2555.
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Breakdown of Current CAD Treatment
US
Europe
CABG is the current gold-standard of care in
patients with left main multivessel disease
CDC MMWR 200756113-118 Eur Heart J
2005261011-1022 J Am Coll Cardiol
2002391096-1103
52

• Isolated LM includes portion of ostial LAD and
  CX. A lesion would have to be 3x RVD away from
  another lesion to count as a separate lesion. So
  if lesion originates in LM and extends to both
  LAD and CX that would be a LM isolated. Only when
  the RVD criteria is met further down vessel, or
  obviously RCA, does it count as 1/2/3.