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USCV5642.114.0 September 2008 1 of 25 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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USCV5642.114.0 September 2008 2 of 25 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
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USCV5642.114.0 September 2008 3 of 25 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 Patient 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;1:219-227 Valgimigli et al, Am J Cardiol 2007;99:1072-1081 Serruys et al, EuroIntervention 2007;3:450-459 BARI classification of coronary segments Leaman score, Circ 1981;63:285-299 Lesions classification ACC/AHA, Circ 2001;103:3019- 3041 Bifurcation classification, CCI 2000;49:274-283 CTO classification, J Am Coll Cardiol 1997;30:649-656 No. & Location of lesion LeftMain Tortuosity 3 Vessel Thrombus Bifurcation CTO Calcification SYNTAXSCORE Dominance
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USCV5642.114.0 September 2008 4 of 25 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 SYNTAX Primary Endpoint Randomized 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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USCV5642.114.0 September 2008 5 of 25 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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USCV5642.114.0 September 2008 6 of 25 TAXUS n=903 PCI n=198 CABG n=1077 CABG n=897 no f/u n=428 5yr f/u n=649 PCI all captured w/ follow up CABG 2500 750 w/ f/u vs Total enrollment N=3075 Stratification: LM and Diabetes Two Registry Arms Randomized Arms n=1800 Two Registry Arms Randomized Arms n=1800 Heart Team (surgeon & interventionalist) PCI N=198 CABG N=1077 Amenable for only one treatment approach TAXUS * N=903 CABG N=897 vs Amenable for both treatment options Stratification: LM and Diabetes LM 33.7% 3VD 66.3% LM 34.6% 3VD 65.4% 23 US Sites62 EU Sites + SYNTAX Trial Design * TAXUS ® Express ® Stent
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USCV5642.114.0 September 2008 7 of 25 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=903 PCI n=198 CABG n=1077 CABG n=897 no f/u n=428 5yr f/u n=649 PCI all captured w/ follow up CABG 2500 750 w/ f/u vs Total enrollment N=3075 Stratification: LM and Diabetes Two Registry Arms Randomized Arms n=1800 Two Registry Arms Randomized Arms n=1800 Heart Team (surgeon & interventionalist) PCI N=198 CABG N=1077 Amenable for only one treatment approach TAXUS * N=903 CABG N=897 vs Amenable for both treatment options Stratification: LM and Diabetes LM 33.7% 3VD 66.3% LM 34.6% 3VD 65.4% DM 28.5% Non DM 71.5% NonDM 71.8% DM 28.2% 23 US Sites62 EU Sites + SYNTAX Trial Design * TAXUS ® Express ® Stent
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USCV5642.114.0 September 2008 8 of 25 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 Patient Characteristics (l) Patient Characteristics (l) Randomized Cohort CABG N=897 TAXUS* N=903 P value Age, mean ± SD (y)65.0 ± 9.8 65.2 ± 9.7 0.55 Male, %78.976.40.20 BMI, mean ± SD27.9 ± 4.5 28.1 ± 4.8 0.37 Diabetes, %28.528.20.89 Hypertension, %77.074.00.14 Hyperlipidemia, %77.278.70.44 Current smoker, %22.018.50.06 Prior MI, %33.831.90.39 Unstable angina, %28.028.90.67 Additive EuroSCORE, mean ± SD3.8 ± 2.7 3.8 ± 2.6 0.78 Total Parsonnet score, mean ± SD8.4 ± 6.8 8.5 ± 7.0 0.76 * TAXUS ® Express ® Stent
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USCV5642.114.0 September 2008 9 of 25 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 Patient Characteristics (lI) Randomized Cohort Patient-based CABG N=897 TAXUS* N=903 P value Total SYNTAX Score29.1 ±11.4 28.4 ±11.5 0.19 Diffuse disease or small vessels, %10.711.30.69 No. lesions, mean ± SD4.4 ±1.8 4.3 ±1.8 0.44 3VD only, %66.365.40.70 Left main, any, %33.734.60.70 Left Main only3.13.80.46 Left Main + 1 vessel5.15.40.78 Left Main + 2 vessel12.011.50.72 Left Main + 3 vessel13.513.90.78 Total occlusion, %22.224.20.33 Bifurcation, %73.372.40.67 Trifurcation, %10.610.70.92 * TAXUS ® Express ® Stent
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USCV5642.114.0 September 2008 10 of 25 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 Procedural Characteristics PCI Randomized Cohort * TAXUS ® Express ® Stent Staged procedure, %14.1 Lesions treated/pt, mean ± SD3.6 ± 1.6 No. stents implanted, mean ± SD4.6 2.3 Total length implanted, mm ± SD86.1 47.9 Range, mm8 – 324 Long stenting (>100 mm), %33.2 TAXUS* N=903 Patient-based
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USCV5642.114.0 September 2008 11 of 25 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 Procedure-related CABG N=897 Off-pump surgery, %15.0 Graft revascularization, % Complete arterial revascularization18.9 At least one arterial graft97.3 Double LIMA/RIMA27.6 LIMA+venous78.1 Arterial graft to LAD95.6 Radial Artery14.1 Venous graft only2.6 Grafts per patient, mean ± SD2.8 0.7 Distal anastomosis/pt, mean ± SD3.2 0.9 Procedural Characteristics CABG Randomized Cohort
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USCV5642.114.0 September 2008 12 of 25 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 Event Rate ± 1.5 SE ITT population # Fisher Exact Test P=0.37 # All-cause Death to 12 Months 4.3% 3.5% 0612 10 20 0 Months Since Allocation Cumulative Event Rate (%) TAXUS* (N=903) CABG (N=897) * TAXUS ® Express ® Stent
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USCV5642.114.0 September 2008 13 of 25 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 Cerebrovascular Events to 12 Months 0.6% 2.2% 0612 10 20 0 Months Since Allocation Cumulative Event Rate (%) P=0.003 # Event Rate ± 1.5 SE ITT population #Fisher Exact Test * TAXUS ® Express ® Stent TAXUS* (N=903) CABG (N=897)
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USCV5642.114.0 September 2008 14 of 25 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 Myocardial Infarction to 12 Months 3.2% 4.8% 0612 10 20 0 Months Since Allocation Cumulative Event Rate (%) P=0.11 # Event Rate ± 1.5 SE ITT population # Fisher Exact Test * TAXUS ® Express ® Stent TAXUS* (N=903) CABG (N=897)
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USCV5642.114.0 September 2008 15 of 25 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 Death/CVA/ MI to 12 Months P=0.98 # 0612 10 20 0 Months Since Allocation Cumulative Event Rate (%) 7.7% 7.6% Event Rate ± 1.5 SE ITT population # Fisher Exact Test * TAXUS ® Express ® Stent TAXUS* (N=903) CABG (N=897)
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USCV5642.114.0 September 2008 16 of 25 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 Symptomatic Graft Occlusion & Stent Thrombosis at 12 Months3.33.4 P=0.89 CABGTAXUS Patients (%) N=27N=28 TAXUS* (N=903) CABG (N=897) ITT population * TAXUS ® Express ® Stent
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USCV5642.114.0 September 2008 17 of 25 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 Repeat Revascularization to 12 Months 5.9% 13.7% 0612 10 20 0 Months Since Allocation Cumulative Event Rate (%) P<0.0001 # Repeat Revasc CABG Group PCI Group PCI4.7%11.4% CABG1.3%2.8% Event Rate ± 1.5 SE ITT population # Fisher Exact Test * TAXUS ® Express ® Stent TAXUS* (N=903) CABG (N=897)
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USCV5642.114.0 September 2008 18 of 25 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 MACCE to 12 Months P=0.0015 # 0612 10 20 0 Months Since Allocation Cumulative Event Rate (%) 12.1% 17.8% Event Rate ± 1.5 SE ITT population # Fisher Exact Test * TAXUS ® Express ® Stent TAXUS* (N=903) CABG (N=897)
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USCV5642.114.0 September 2008 19 of 25 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 Primary Endpoint:12 Month MACCE Non-inferiority Analysis Non-inferiority comparison was not met for the primary endpoint, further comparisons for the LM and 3VD subgroups are observational only and hypothesis generating 05%10%15% Pre-specified Margin = 6.6% Difference in MACCE 20% +95% CI = 8.3% 5.5%
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USCV5642.114.0 September 2008 20 of 25 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 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%) CABGTAXUS* Patients (%) All LM N=705 Comparisons for the LM and 3VD subgroups are observational only and hypothesis generating * TAXUS ® Express ® Stent
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USCV5642.114.0 September 2008 21 of 25 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 Left Main and Three Vessel Disease Subgroup MACCE Rates at 12 Months CABGTAXUS* Patients (%) All LM N=705 LM+1VD N=138 LM isolated N=91 LM+2VD N=218 LM+3VD N=258 Comparisons for the LM and 3VD subgroups are observational only and hypothesis generating 3VD (All) N=1095 * TAXUS ® Express ® Stent
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USCV5642.114.0 September 2008 22 of 25 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 Medically Treated Diabetes and Non-Diabetic All-Cause Death/CVA/MI and MACCE at 12 Months ITT population * TAXUS ® Express ® Stent Diabetes (Medical Treatment) N=452 Non-Diabetic N=1348 TAXUS* CABG Death/CVA/MI MACCE Death/CVA/MI MACCE P=0.96 P=0.0025 P=0.08 P=0.97
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USCV5642.114.0 September 2008 23 of 25 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 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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USCV5642.114.0 September 2008 24 of 25 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 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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USCV5642.114.0 September 2008 25 of 25 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 Express 2 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 3.75 mm. Patients with coronary artery lesions longer than 28 mm or requiring more than one TAXUS stent Patients 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
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