USCV5642.114.0 September 2008 1 of 25 The safety and effectiveness of the TAXUS Express2 Stent...

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The safety and effectiveness of the TAXUS Express2 Stent System have not been established in the following patient populations: patients with vessel thrombus at the lesion site; patients with coronary artery lesions longer than 28 mm or requiring more than one TAXUS stent; lesions located in the unprotected left main coronary artery, or lesions located at a bifurcation/trifurcation; patients with moderate or severe calcification in the lesion or a chronic total occlusion; or patients with multi-vessel disease or patients with diabetes

Studying the roles of CABG and PCI using DES in the contemporary management of Left Main* and/or Three-Vessel Disease** Patients

SYNTAX (SYNergy between PCI with TAXUS# and cardiac surgery)

#TAXUS® Express® Stent* Isolated or in conjunction with 1, 2, 3VD and ** revascularization for all 3 vascular territories

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Patient ProfilingPatient Profiling

Local Heart team (surgeon & interventional cardiologist) will assess each patient in regards to:

Patient’s operative risk (EuroSCORE & Parsonnet score)

Coronary lesion complexity (Newly developed SYNTAX score)

– The goal of the SYNTAX score is to provide a tool to assist physicians in their revascularization strategies for patients with high risk lesions

Sianos et al, EuroIntervention 2005;1:219-227Valgimigli et al, Am J Cardiol 2007;99:1072-1081Serruys et al, EuroIntervention 2007;3:450-459

BARI classification of coronary segmentsLeaman score, Circ 1981;63:285-299Lesions classification ACC/AHA , Circ 2001;103:3019-3041 Bifurcation classification, CCI 2000;49:274-283CTO classification, J Am Coll Cardiol 1997;30:649-656

Dominance

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SYNTAX Primary EndpointSYNTAX Primary EndpointRandomized TrialRandomized Trial

The Primary Clinical Endpoint is the 12 Month Major Cardiovascular or Cerebrovascular Event

Rate (MACCE *)MACCE is defined as:• All cause Death• Cerebrovascular Event (Stroke)• Documented Myocardial Infarction• Any Repeat Revascularization (PCI and/or CABG)

All events CEC Adjudicated

*ARC MACCE definition Circ 2007; 115:2344-2351

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71% enrolled (N=3,075)

All Pts with de novo 3VD and/or LM disease (N=4,337)

Treatment preference (9.4%) Referring MD or pts. refused

informed consent (7.0%) Inclusion/exclusion (4.7%) Withdrew before consent (4.3%) Other (1.8%) Medical treatment (1.2%)

23 US Sites62 EU Sites +

SYNTAX Trial Design

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TAXUSn=903

PCIn=198

CABGn=1077

CABGn=897

no f/un=428

5yr f/un=649

PCIall captured w/

follow up

CABG2500

750 w/ f/uvsvs

Total enrollment N=3075

Stratification: LM and Diabetes

Two Registry ArmsRandomized Armsn=1800


Heart Team (surgeon & interventionalist)

PCIN=198

CABGN=1077

Amenable for only one treatment approach

TAXUS*

N=903 CABG

N=897vsvs

Amenable for bothtreatment options


LM33.7%

3VD66.3%

LM34.6%

3VD65.4%


SYNTAX Trial Design

* TAXUS® Express® Stent

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71% enrolled (N=3,075)

All Pts with de novo 3VD and/or LM disease (n=4,337)

Treatment preference (9.4%) Referring MD or pts. refused

informed consent (7.0%) Inclusion/exclusion (4.7%) Withdrew before consent (4.3%) Other (1.8%) Medical treatment (1.2%)TAXUS

n=903PCI

n=198CABG

n=1077CABGn=897

no f/un=428

5yr f/un=649

PCIall captured w/

follow up

CABG2500

750 w/ f/uvsvs

Total enrollment N=3075




Heart Team (surgeon & interventionalist)

PCIN=198

CABGN=1077

Amenable for only one treatment approach

TAXUS*

N=903 CABG

N=897vsvs

Amenable for bothtreatment options


LM33.7%

3VD66.3%

LM34.6%

3VD65.4%

DM 28.5%

Non DM71.5%

NonDM71.8%

DM28.2%


SYNTAX Trial Design


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Patient Characteristics (l)Patient Characteristics (l)Randomized Cohort

CABGN=897

TAXUS*N=903 P value

Age, mean ± SD (y) 65.0 ± 9.8 65.2 ± 9.7 0.55

Male, % 78.9 76.4 0.20

BMI, mean ± SD 27.9 ± 4.5 28.1 ± 4.8 0.37

Diabetes, % 28.5 28.2 0.89

Hypertension, % 77.0 74.0 0.14

Hyperlipidemia, % 77.2 78.7 0.44

Current smoker, % 22.0 18.5 0.06

Prior MI, % 33.8 31.9 0.39

Unstable angina, % 28.0 28.9 0.67

Additive EuroSCORE, mean ± SD 3.8 ± 2.7 3.8 ± 2.6 0.78

Total Parsonnet score , mean ± SD 8.4 ± 6.8 8.5 ± 7.0 0.76* TAXUS® Express® Stent

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Patient Characteristics (lI)Randomized Cohort

Patient-basedCABG

N=897TAXUS*N=903 P value

Total SYNTAX Score 29.1 ±11.4 28.4 ±11.5 0.19

Diffuse disease or small vessels, % 10.7 11.3 0.69

No. lesions, mean ± SD 4.4 ±1.8 4.3 ±1.8 0.44

3VD only, % 66.3 65.4 0.70

Left main, any, % 33.7 34.6 0.70

Left Main only 3.1 3.8 0.46

Left Main + 1 vessel 5.1 5.4 0.78



Total occlusion, % 22.2 24.2 0.33

Bifurcation, % 73.3 72.4 0.67

Trifurcation, % 10.6 10.7 0.92* TAXUS® Express® Stent

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Procedural CharacteristicsPCI Randomized Cohort


Staged procedure, % 14.1

Lesions treated/pt, mean ± SD 3.6 ± 1.6

No. stents implanted, mean ± SD 4.6 2.3

Total length implanted, mm ± SD 86.1 47.9

Range, mm 8 – 324

Long stenting (>100 mm), % 33.2

TAXUS*N=903Patient-based

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Procedure-related CABG

N=897

Off-pump surgery, % 15.0

Graft revascularization, %

Complete arterial revascularization

18.9

At least one arterial graft 97.3

Double LIMA/RIMA 27.6

LIMA+venous 78.1

Arterial graft to LAD 95.6

Radial Artery 14.1

Venous graft only 2.6

Grafts per patient, mean ± SD 2.8 0.7

Distal anastomosis/pt, mean ± SD 3.2 0.9

Procedural CharacteristicsProcedural CharacteristicsCABG Randomized CohortCABG Randomized Cohort

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Event Rate ± 1.5 SEITT population#Fisher Exact Test

P=0.37#

All-cause Death to 12 Months All-cause Death to 12 Months

4.3%3.5%

0 6 12

10

20

0

Months Since Allocation

Cu

mu

lati

ve E

ven

t R

ate

(%

)

TAXUS* (N=903)CABG (N=897)


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Cerebrovascular Events to 12 Months Cerebrovascular Events to 12 Months

0.6%2.2%

0 6 12

10

20

0


Cu

mu

lati

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ven

t R

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(%

) P=0.003#




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Myocardial Infarction to 12 Months Myocardial Infarction to 12 Months

3.2%4.8%

0 6 12

10

20

0


Cu

mu

lati

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ven

t R

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(%

) P=0.11#




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Death/CVA/ MI to 12 Months

P=0.98#

0 6 12

10

20

0


Cu

mu

lati

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ven

t R

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(%

)

7.7% 7.6%




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Symptomatic Graft Occlusion & Stent Thrombosis at 12 Months

3.33.33.43.4

P=0.89

CABGCABG TAXUSTAXUS

Pati

en

ts (

%)

N=27N=27 N=28N=28


ITT population* TAXUS® Express® Stent

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Repeat Revascularization to 12 MonthsRepeat Revascularization to 12 Months

5.9%

13.7%

0 6 12

10

20

0


Cu

mu

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(%

) P<0.0001#

Repeat Revasc

CABG Group

PCI Group

PCI 4.7% 11.4%

CABG 1.3% 2.8%




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MACCE to 12 Months

P=0.0015#

0 6 12

10

20

0


Cu

mu

lati

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t R

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(%

)

12.1%

17.8%




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Primary Endpoint:12 Month MACCE Non-inferiority Analysis

Non-inferiority comparison was not met for the primary Non-inferiority comparison was not met for the primary endpoint, further comparisons for the LM and 3VD subgroups endpoint, further comparisons for the LM and 3VD subgroups are observational only and hypothesis generating are observational only and hypothesis generating

0 5% 10% 15%

Pre-specified Margin = 6.6%Pre-specified Margin = 6.6%

Difference in MACCEDifference in MACCE20%

+95% CI = 8.3%5.5%

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Left Main Subgroup MACCE Rates at 12 Months

Left Main Isolated

Left Main + 3VD

Left Main + 2VD

Left Main + 1VD

N=258(37%)

N=218(31%)

N=138(20%)

N=91(13%

)

CABG TAXUS*

Pati

en

ts (

%)

All LMN=705

Comparisons for the LM and 3VD subgroups are observational only and hypothesis generating * TAXUS® Express® Stent

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Left Main and Three Vessel Disease Subgroup MACCE Rates at 12 Months

CABG TAXUS*

Pati

en

ts (

%)

All LMN=705

LM+1VDN=138

LM isolatedN=91

LM+2VDN=218

LM+3VDN=258

Comparisons for the LM and 3VD subgroups are observational only and hypothesis generating

3VD (All)N=1095


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Medically Treated Diabetes and Non-DiabeticMedically Treated Diabetes and Non-DiabeticAll-Cause Death/CVA/MI and MACCE at 12 MonthsAll-Cause Death/CVA/MI and MACCE at 12 Months

ITT population * TAXUS® Express® Stent

Diabetes (Medical Treatment)N=452

Non-DiabeticN=1348

TAXUS*CABG

Death/CVA/MI MACCE Death/CVA/MI MACCE

P=0.96 P=0.0025 P=0.08P=0.97

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Conclusions: I

The SYNTAX randomized trial is a unique comparison of the utility of contemporary CABG and PCI with drug-eluting TAXUS® Express® stents in the most challenging groups of patients, those with Left Main* and/or Three Vessel** coronary disease

The trial attempted an ‘all-comers’ strategy with the minimum of exclusion criteria

The complexity of the patients recruited into the SYNTAX trial are unique in the field to date

* Isolated or in conjunction with 1, 2, 3VD and ** revascularization for all 3 vascular territories

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Conclusions: II

Non-inferiority comparison was not met for the primary endpoint

In the randomized SYNTAX cohort, there were comparable overall safety outcomes (Death, CVA, MI,) in CABG and PCI patients at 12 months (7.7 vs. 7.6%).

• There was a significantly higher rate of revascularization in the PCI group (13.7 vs. 5.9 %), and a significantly higher rate of CVA in the CABG group (2.2 vs. 0.6%).

• Overall MACCE in the PCI group was higher (17.8 vs. 12.1%) due to an excess of redo revascularization compared with CABG.

• Per protocol rates of symptomatic graft occlusion and stent thrombosis were similar.

• The goal of the SYNTAX score is provide a tool to assist physicians in their revascularization strategies for patients with high risk lesions

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Indications The TAXUS Express2 Paclitaxel-Eluting Coronary Stent System is indicated for improving luminal diameter for the treatment of de novo lesions ≤ 28 mm in length in native coronary arteries ≥ 2.5 to ≤ 3.75 mm in diameter.

Contraindications Use of the TAXUS Express2 Paclitaxel-Eluting Coronary Stent System is contraindicated in patients with: Known hypersensitivity to paclitaxel or structurally-related compounds. Known hypersensitivity to the polymer or its individual components (see details in TAXUS Express2 Stent System DFU). Coronary Artery Stenting is contraindicated for use in: Patients who can not receive recommended anti-platelet and/or anticoagulant therapy. Patients judged to have a lesion that prevents complete inflation of an angioplasty balloon or proper placement of the stent or delivery device.

Warnings To maintain sterility, the inner package should not be opened or damaged prior to use. The use of this product carries the risks associated with coronary artery stenting, including subacute thrombosis, vascular complications, and/or bleeding events. Patients with known hypersensitivity to 316L stainless steel may suffer an allergic reaction to this implant. This product should not be used in patients who are not likely to comply with recommended antiplatelet therapy.

Potential Adverse Effects Potential adverse events (in alphabetical order) which may be associated with the use of a coronary stent in native coronary arteries include but are not limited to: Aneurysm, Arrhythmias, Bleeding complications, Death, Distal Emboli, Emergent CABG, Myocardial Infarction, Myocardial Ischemia, Occlusion, Stent Delivery Failures, Target Lesion Revascularization, Thrombosis, Vascular complications, Vessel Dissection. Potential adverse events not captured above that may be unique to the paclitaxel drug coating: Alopecia, Allergic reaction to the drug or the polymer, Anemia, Blood product transfusion, Gastrointestinal symptoms, Hematologic dyscrasia, Hepatic enzyme changes, Histologic changes in vessel wall, including inflammation, cellular damage or necrosis, Myalgia/Arthralgia, Peripheral neuropathy. The safety and effectiveness of the TAXUS™ Express® Stent have not been established in the cerebral, carotid, or peripheral vasculature or the following patient populations: Patients with vessel thrombus at the lesion site. Patients with coronary artery reference vessel diameters < 2.5 or > 3.75 mm. Patients with coronary artery lesions longer than 28 mm or requiring more than one TAXUS stentPatients with lesions located in the saphenous vein grafts, in the unprotected left main coronary artery, ostial lesions, or lesions located at a bifurcation. Patients with diffuse disease or poor flow distal to the identified lesions. Patients with tortuous vessels (>60 degrees) in the region of the obstruction or proximal to the lesion. Patients with a recent acute myocardial infarction where there is evidence of thrombus or poor flow. Patients with in-stent restenosis. Patients with moderate or severe calcification in the lesion or a chronic total occlusion. Patients with multi-vessel disease.Prior to use, please see the complete "Directions for Use" at www. Taxus-stent.com for more information on Indications, Contraindications, Warnings, Precautions, Adverse Events and Operator's Instructions.

Cautions Federal law restricts this product to sale by or on the order of a physician. Trademark TAXUS, PROMUS and Express² are trademarks and Express is a registered trademark of Boston Scientific Corporation or its affiliates. Cypher is a trademark of Cordis Corporation. Endeavor is a trademark of Medtronic Vascular, Inc. Plavix is a trademark of Sanofi-Aventis. CoStar is a trademark of Conor MedSystems, Inc.PROMUS Stent is a private-labeled XIENCE V Everolimus Eluting Coronary Stent System manufactured by Abbott and distributed by Boston Scientific Corporation. XIENCE is a trademark of Abbott Laboratories group of companies. NIR is a trademark of Medinol, Jerusalem, Israel.

TAXUS® Express® Stent System Abbreviated Statement

USCV5642.114.0 September 2008 1 of 25 The safety and effectiveness of the TAXUS Express2 Stent...

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