Presentation on theme: "The TAXUS™ Paclitaxel-Eluting Stent Program. The safety and effectiveness of the TAXUS ™ Express 2 ™ Stent has not been established in patients with coronary."— Presentation transcript:
The safety and effectiveness of the TAXUS ™ Express 2 ™ Stent has not been established in patients with coronary artery reference vessel diameters less than 2.5 mm or in lesions longer than 28 mm or in patients with diabetes
Table of Contents Drug-eluting stent overview Drug-eluting stent benefits In your opinion … Part 1 –Consistently low revascularization rates In your opinion … Part 2 –Excellent safety with desirable healing In your opinion … Part 3 –Ability to treat various patients and lesions What does the future hold?
Drug-Eluting Stent Overview From Bare Metal to Drug-Eluting Stents Key Bare Metal Stent Characteristics Key Drug-Eluting Stent Characteristics Healing Restenosis Reduction Deliverability and Conformability Binary restenosisDramatic TLR/TVR reduction Consistent performance throughout the target lesion Predictable results across all patient subsets Various lesion access Excellent conformability Minimize incomplete apposition Deliverability Desirable late loss Complete endothelialization Wide margin of safety Large lumens
Drug-Eluting Stent Benefits Reduced angiographic restenosis Reduced clinical restenosis Comparable safety compared to bare-metal stents Improved patient outcomes Positive trends in various lesion subsets Positive trends in various patient populations
In your opinion... Which patients should receive drug-eluting stents? What factors are critical to consider when trying to minimize repeat revascularizations? What are the most important components of a drug-eluting stent and why?
TAXUS IV Clinical Trial TLR Overall at 9 Months RR=0.27 [0.16-0.43] P<0.0001 P=0.48 RR=0.39 [0.26-0.59] P<0.0001 Event % *= Express® Control Stent. **= TAXUS™ Express® Stent
RR=0.29 [0.19-0.43] P<0.0001 P=0.74 RR=0.41 [0.29-0.57] P<0.0001 Event % TAXUS IV Clinical Trial TLR Overall at 12 Months *= Express® Control Stent. **= TAXUS™ Express® Stent
TAXUS IV Clinical Trial TLR/TVR Overall at 9 Months P<0.0001 P=0.0008P=0.005P=0.0001 Event % *= Express® Control Stent. **= TAXUS™ Express® Stent
P<0.0001 P=0.0003P=0.0120P<0.0001 Event % TAXUS IV Clinical Trial TLR/TVR Overall at 12 Months *= Express® Control Stent. **= TAXUS™ Express® Stent
Impact of Diabetes Mellitus TAXUS IV Clinical Trial TLR at 9 Months P=0.004 P=0.32 P<0.0001 N=489N=507N=109N=104N=54N=51 *= Express® Control Stent. **= TAXUS™ Express® Stent
P<0.0001 P=0.12 N=489N=507 N=109N=104N=54N=51 P=0.0063 Impact of Diabetes Mellitus TAXUS IV Clinical Trial TLR at 12 Months *= Express® Control Stent. **= TAXUS™ Express® Stent
P<0.0001 P=0.057 P=0.0004 RVD (mm) N=214N=206 N=241N=257N=195N=197 Impact of Vessel Diameter (QCA) TAXUS IV Clinical Trial TLR at 9 Months *= Express® Control Stent. **= TAXUS™ Express® Stent
Impact of RVD (visual assessment) TAXUS IV Clinical Trial TLR at 9 Months P<0.0001 P=0.0001 N=154N=150N=498N=511 *= Express® Control Stent. **= TAXUS™ Express® Stent
Impact of Stent Diameter TAXUS IV Clinical Trial TLR at 9 Months P=0.0001 P=0.002 P=0.0002 Stent diameter (mm) N=133N=131N=304N=323 N=206 N=197 *= Express® Control Stent. **= TAXUS™ Express® Stent
P=0.01 P=0.0009 P=0.0001 Lesion length (mm) N=226N=214 N=325N=351 N=97N=91 Impact of Lesion Length (QCA) TAXUS IV Clinical Trial TLR at 9 Months *= Express® Control Stent. **= TAXUS™ Express® Stent
Impact of Total Stent Length TAXUS IV Clinical Trial TLR at 9 Months P=0.002 P<0.0001 P=0.0004 Stent length (mm) N=382N=372 N=127 N=126 N=134N=153 *= Express® Control Stent. **= TAXUS™ Express® Stent
TLR (%) Lesion Length (mm) Control TAXUS™ Stent Lesion Length Response (tertile analysis) TAXUS IV Clinical Trial TLR at 9 Months > 3.0 2.5-3.0 < 2.5 RVD (mm)
TAXUS IV Clinical Trial Restenosis at 9 Months RR=0.23 [0.13, 0.38] P<0.0001 RR=0.30 [0.19, 0.46] P<0.0001 Restenosis (%) *= Express® Control Stent. **= TAXUS™ Express® Stent
TAXUS IV Clinical Trial Restenosis Impact of Vessel Diameter (QCA) P<0.0001 P=0.10 P=0.0001 RVD (mm) N=78N=98N=97N=105N=92N=88 In-Segment Restenosis (%) *= Express® Control Stent. **= TAXUS™ Express® Stent
N=49N=57 TAXUS IV Clinical Trial Restenosis Impact of Stent Diameter P=0.0002 P=0.13 P<0.0001 Stent diameter (mm) N=125N=143N=93N=91 In-Segment Restenosis (%) *= Express® Control Stent. **= TAXUS™ Express® Stent
Reduced In-Stent Binary Restenosis No Edge Effect in TAXUS IV Clinical Trial % of patients 26.6 7.9 Intent-to-treat, angiographic subset (n=732) 3.4 2.7 24.4 5.5 1.9 0.7 P=0.81 P=0.27 P<0.001 *= Express® Control Stent. **= TAXUS™ Express® Stent
9-Month % Diameter Stenosis Improved In-Stent and at Both Edges in TAXUS IV Clinical Trial % Diameter Stenosis 39.8 26.3 P<0.0001 Intent-to-treat, angiographic subset (n=732) 16.1 13.2 37.2 17.4 11.8 7.6 P=0.0167 P<0.0001 P=0.0001 *= Express® Control Stent. **= TAXUS™ Express® Stent
0.0 1.0 2.0 3.0 0-3mm3-6mm6-9mm 9-12mm 12-15mm Neointimal hyperplasia area [mm 2 ] P=ns TAXUS II Clinical Trial Uniform Suppression of Neointima at 6 Months IVUS analysis of TAXUS II clinical trial patients showed uniform neointimal suppression throughout the entire stent 0-3mm3-6mm6-9mm 9-12mm 12-15mm TAXUS™ Stent** Control* proximal distalproximal distal *= Express® Control Stent. **= TAXUS™ Express® Stent
Neointimal area (mm 2 ) 0 1 2 3 4 proximal distalproximal distal Control* TAXUS™ Stent** IVUS analysis of TAXUS IV clinical trial patients showed uniform neointimal suppression throughout the entire stent TAXUS IV Clinical Trial Uniform Suppression of Neointima at 9 Months P=ns 0-3mm3-6mm6-9mm 9-12mm 12-15mm 0-3mm3-6mm6-9mm 9-12mm 12-15mm *= Express® Control Stent. **= TAXUS™ Express® Stent
The multifunctional effects of a drug may contribute to reducing restenosis Polymeric coatings may provide uniform drug delivery across the stent High degrees of lipophilicity may increase vascular absorption in the tissue surrounding the stent Minimal overhang may potentially reduce trauma at the edges Restenosis Reduction Formula for Fighting Restenosis Multifunctional Effects Uniform Drug Delivery Rapid Drug Absorption Balloon Overhang Several drug-eluting stent characteristics may contribute to restenosis reduction.
Microtubule Network: Paclitaxel promotes the formation of stable microtubules, thereby inhibiting multiple cellular functions Note: Image Courtesy of Dr. Vladimir Rodionov Restenosis Reduction Multifunctional Activity The TAXUS TM Stent elutes paclitaxel, a multifunctional microtubular inhibitor. Paclitaxel is believed to have multifunctional effects which reduce: –Inflammation –Proliferation and migration of smooth muscle cells –Extra-cellular matrix secretion
Restenosis Reduction Paclitaxel and Taxol are Different *Based on Implantation of a Single 3.5mm X 16mm TAXUS™ Express 2™ Stent with Total Loaded Dose of 108 g. Dose in g/kg Calculated Using Average Body Surface Area of 1.7m 2 and 70kg Body Weight. Note: Taxol is a registered trademark of Bristol Meyers Squibb.
Paclitaxel Wide Safety Window Paclitaxel’s broad safety window inhibits smooth muscle cell proliferation & migration while allowing the vessel to heal.
Paclitaxel is a multi-functional drug which appears to: –Inhibit proliferation –Inhibit migration –Inhibit inflammation –Inhibit secretion Healing Paclitaxel Promotes Endothelialization Restenosis Prevents The TAXUS™ paclitaxel-eluting stent appears not to delay endothelialization Complete endothelialization of a paclitaxel-eluting stent in a porcine coronary artery. Endothelial cells are less sensitive than smooth muscle cells to the effects of paclitaxel.
Translute Polymer is intended to control the release of the drug during the critical period of the restenotic cascade Restenosis Reduction Uniform Drug Distribution The Translute TM Polymer provides protection and controlled release of paclitaxel. Translute Polymer is intended to protect the drug during crimping, packaging, distribution, preparation, sterilization, delivery to the lesion, and stent expansion
Restenosis Reduction Lipophilicity Outside the cell Inside the cell Paclitaxel (green) Lipid Bi-Layer Paclitaxel is highly lipophilic which may increase vascular absorption in tissue surrounding the stent.
In controlled clinical studies, use of the TAXUS™ Stent resulted in consistently low revascularization rates across a broad range of patient and lesion types
In your opinion... How do you define “safety” as it relates to drug-eluting stents? Do you believe that late loss is an indication of efficacy, safety or both? How important is late loss? What affects vascular healing after stent implantation?
TAXUS IV Clinical Trial 9-Month MACE and TVF P=0.80P=0.88P<0.0001P=0.0002P=0.0001P<0.0001 Event (%) *= Express® Control Stent. **= TAXUS™ Express® Stent
P=1.00P<0.0001P=0.33P<0.0001 Event (%) TAXUS IV Clinical Trial 12-Month MACE and TVF *= Express® Control Stent. **= TAXUS™ Express® Stent
TAXUS IV Clinical Trial Stent Thrombosis at 12 Months 0.3 0.2 0.3 00.20.40.60.81 Control* (n=652) TAXUS™ Stent** (n=662) In-hospitalDischarge - 30 days 31 days - 6 months12 months P=0.75 Stent thrombosis, % 0.6% (n=4) 0.8% (n=5) Note: There were no additional stent thrombosis between 6 and 9 months in either the TAXUS Stent or Control. *= Express® Control Stent. **= TAXUS™ Express® Stent
Healing Late Loss Late loss provides evidence of healing A drug-eluting stent should not completely eliminate the body’s healing response Neointima indicates healing after drug-eluting stent implantation Consistently low but positive late loss values across studies may indicate healing Image Courtesy of Dr. Robert Schwartz
Healing Late Loss in Bare Metal Stents Late loss in bare metal stents is typically 1.0mm Late loss is thought to be largely comprised of neointima Late loss is nearly always a positive number, indicating the lumen decreases in size MLD post-procedure MLD follow-up 0.50mm Late Loss 1.0mm + Illustrations by Boston Scientific. Images not to scale.
Healing Late Loss in Bare Metal Stents The Express 2™ Stent strut thickness is 0.0052”, which converts to 0.13mm This is well within the amount of late loss of a bare metal stent, suggesting complete stent strut coverage MLD follow up 0.13mm 0.50mm 0.0052”= 0.13mm Illustrations by Boston Scientific. Images not to scale. Lumen Neointima
Healing TAXUS IV Clinical Trial Late Loss to Strut Thickness Relationship The Express 2 ™ Stent strut thickness is 0.0052”, which converts to 0.13mm Based on the TAXUS IV trial late loss values, neointima would be sufficient to completely cover the stent struts. Illustrations by Boston Scientific. Images not to scale. MLD follow up 0.130mm 0.195mm 0.0052”= 0.13mm Lumen Neointima
Healing Paclitaxel Selective Impact Low but positive late loss provides evidence that vessel healing has occurred. Paclitaxel allows healing to occur within the vessel, as evidenced by low but positive late loss. Late loss =~0.30mm 0.15 mm 0.30 mm Paclitaxel IC50 (nM) Note: Image courtesy of Dr. Robert Schwartz; In vitro cell culture study performed by Dr. Luszher Endothelial cells are less sensitive than smooth muscle cells to the effects of Paclitaxel.
Late loss <0.6 mm weak predictor of TLR Probability for TLR (%) Late Loss (mm) 100 0 50 0.001.002.501.500.502.00 Late loss >0.6mm increasing probability of TLR TAXUS IV Clinical Trial Late loss as a Predictor of TLR Logistic regression combining all patients
TAXUS IV Clinical Trial Late loss as a Predictor of Restenosis Probability for Restenosis (%) Late Loss (mm) 100 0 50 0.001.002.501.500.502.00 Late loss >0.6 increasing probability of restenosis Logistic regression combining all patients
In animal and controlled human clinical studies, the TAXUS™ stent consistently demonstrated excellent safety with desirable healing
In your opinion... What role does the stent platform play in terms of drug-eluting stent safety and efficacy? Why is conformability important with drug-eluting stents? What tradeoffs are you willing to make as it relates to stent designs?
Deliverability and Conformability Excellent deliverability and conformability will continue to be important features with drug-eluting technology… Bare Metal Stents (Desired Features) Drug-Eluting Stents (Desired Features) Deliverability: - access lesions Conformability Deliverability: - access more lesions with longer stents when necessary Conformability: - provide strut apposition to the vessel for uniform coverage and drug absorption
Stent apposition contributes to efficacy and safety The Express 2 Stent platform was designed for excellent deployment with excellent stent to vessel conformability. 9 atm Working Range* 15 atm 1.1:1 18 atm Rated Burst Pressure 14 atm Quarter Size 9 atm Nominal Express 2™ Stent3.0 mm System A broad working range and high RBP combine to provide excellent sizing flexibility. A conformable stent provides uniform strut apposition to the vessel wall.
Importance of Stent Apposition Contact between the vessel wall and the stent strut may be essential for drug absorption. Uniform stent apposition allows for uniform drug absorption and uniform restenosis reduction. Incomplete stent apposition / under-deployment may increase the risk of thrombus formation & SAT’s. Achieving proper stent strut apposition may be a key contributor to both efficacy and safety of drug eluting stents, specifically SATs. Efficacy (Restenosis Reduction) Safety (Healing)
–A recent study noted that “78% of SAT occurs in arteries with stent under - deployment 1,” highlighting the importance of stent deployment and apposition 1 Cheneau, et al. Circulation 2003;108;43-47 Incomplete Apposition Under - deployment and incomplete apposition increase the risk of SAT Safety Sub Acute Thrombosis (SAT)
TAXUS IV Clinical Trial Correlation of Incomplete Apposition and Safety 0% TLR 0% Non-Q-wave MI 0% Stent thrombosis 0% TVR overall 0% Q-wave MI 0% Cardiac death 0% MACE overall Acquired IA (n=3) Persistent IA (n=4) Resolved IA (n=11) The TAXUS™ Stent showed no safety events at 9 months in patients with resolved, persistent or late acquired IA
Excellent deliverability and conformability of the Express ® stent platform makes it easy to treat various patient and lesion types
Drug-Eluting Stent Benefits Summary of Ideal Characteristics DES Polymer StentDrug Deliverability and Conformability Healing TLR and Restenosis Reduction Access to various lesions Strut apposition Sustained TLR and restenosis reduction, within the stent and at the edges Consistent results across patients and lesions Low rates of major adverse events Consistently low and desirable late loss
TAXUS TM Express 2TM Paclitaxel-Eluting Coronary Stent System INDICATIONS The TAXUS™ Express 2 ™ Paclitaxel-Eluting Coronary Stent System is indicated for improving luminal diameter for the treatment of de novo lesions 2.5 to <3.75 mm in diameter. CONTRAINDICATIONS Use of the TAXUS Express 2 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. Coronary Artery Stenting is contraindicated for use in: Patients in whom antiplatelet and/or anticoagulant therapy is contraindicated. Patients judged to have a lesion that prevents complete inflation of an angioplasty balloon or proper placement of the stent or delivery device.
TAXUS TM Express 2TM Paclitaxel-Eluting Coronary Stent System 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. 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.
TAXUS TM Express 2TM Paclitaxel-Eluting Coronary Stent System The safety and effectiveness of the TAXUS Express 2 Paclitaxel-Eluting Coronary Stent System have not been established in the following patient populations: Women who are pregnant or lactating. Men intending to father children. Pediatric patients. Patients with unresolved vessel thrombus at the lesion site. Patients with coronary artery reference vessel diameters 3.75 mm. 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 multiple overlapping stents. Patients with longer than 12 month follow-up.
TAXUS TM Express 2TM Paclitaxel-Eluting Coronary Stent System 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. CAUTION Federal law restricts this product to sale by or on the order of a physician. TRADEMARKS TAXUS and Express 2 are trademarks and Express is a registered trademark of Boston Scientific Corporation or its affiliates.