6.4 Carcinogenicity, Genotoxicity, and Reproductive Toxicology ............5 Table 9.6.7 HORIZONS AMI Secondary Endpoints by Gender ........16 6.5 Pregnancy ....................................................................................................5 Table 9.6.8 HORIZONS AMI Clinical Endpoints, All TAXUS 2012-06 6.6 Lactation ........................................................................................................5 Express® Male and Female Patients at 30 Days, 1 Year, 2 Years 90776901-01 < EN > and 3 Years (Stent ITT Population) ........................................................16 7 OVERVIEW OF CLINICAL STUDIES ....................................................................5 9.7 Pooled Results of the TAXUS SR stent versus BMS (TAXUS I, II-SR, 7.1 TAXUS Clinical Trials ...................................................................................5 IV, and V de novo) .............................................................................................16 ® 2™ Table 7.1 TAXUS Slow-Release Formulation Trials ..............................6 Table 9.7.1 TAXUS SR ITT Patients Disposition Table (N=2793; TAXUS Express 7.2 ARRIVE Clinical Registry .............................................................................6 TAXUS I, II-SR, IV, and V de novo) .........................................................16 8 ADVERSE EVENTS ................................................................................................6 Figure 9.7.1 Efficacy – Target Vessel Revascularization (TVR) in and 8.1 Observed Adverse Events ..........................................................................6 TAXUS pooled analysis (TAXUS I, II-SR, IV, V de novo; N=2793) .....17 Table 8.1 TAXUS V (ISR and de novo), IV, II, and I Major Adverse Figure 9.7.2 Safety – Mortality in TAXUS pooled analysis (TAXUS I, ® 2™ Cardiac Events (MACE) from Post-Procedure to Latest Follow-Up .6 II-SR, IV, V de novo; N=2793) ...................................................................17 TAXUS Express Table 8.2 HORIZONS AMI Major Adverse Cardiac Events (MACE) Figure 9.7.3 Safety – Myocardial Infarction (MI) in TAXUS pooled from Post-Procedure to Latest Follow-Up .............................................7 analysis (TAXUS I, II-SR, IV, V de novo; N=2793) ................................18 ™ 8.2 Potential Adverse Events ..........................................................................7 9.7.1 Stent thrombosis in TAXUS SR pooled analysis (TAXUS I, II-SR, IV, Atom and V de novo; N=2793)...................................................................................18 9 CLINICAL STUDIES ...............................................................................................7 MONORAIL® 9.1. Results of the TAXUS IV Pivotal Clinical Trial ........................................7 Figure 9.7.4 Stent thrombosis Rates for the TAXUS vs. BMS pooled analysis (TAXUS I, II-SR, IV, V de novo; N=2793) vs. BMS by Table 9.1.1 TAXUS IV Clinical Results ......................................................8 Protocol and ARC Definitions .................................................................19 OVER-THE-WIRE Figure 9.1.1 TAXUS IV Freedom from TVR to 5 Years, Event-Free 9.7.2 Diabetic Patients in TAXUS SR pooled analysis (TAXUS I, II-SR, IV, Survival ± 1.5 SE, Safety Population, All Patients (N=1294) ................8 and V de novo; N=715).....................................................................................19 Paclitaxel-Eluting Coronary Stent System Table 9.1.2 TAXUS IV 9-Month Angiographic and IVUS Results........8 Table 9.7.2 Pooled TAXUS SR Clinical Results for Medically Table 9.1.3 TAXUS IV Protocol Defined Stent Thrombosis* through Treated Diabetic Patients (TAXUS I, II-SR, IV, and V de novo) .........19 TABLE OF CONTENTS 5 Years Safety Population (N=1294) ........................................................8 9.8 ARRIVE Clinical Registry ...........................................................................19 WARNING ...................................................................................................................2 9.2 Results of the TAXUS II SR Supporting Clinical Trial ............................8 2 Figure 9.8.1 Lesion complexity in ARRIVE 1 and 2 combined 2 1 TAXUS EXPRESS AND TAXUS EXPRESS ATOM™ PACLITAXEL- Table 9.2.1 TAXUS® II Clinical Results ...................................................9 (N=7492) ......................................................................................................20 ELUTING CORONARY STENT SYSTEM ................................................................2 Figure 9.2.1 TAXUS II Freedom from TVR to 5 Years, Event-Free 9.8.1 ARRIVE 1 ...................................................................................................20 Table 1.1 TAXUS Express2 and TAXUS Express2 Atom Stent System Survival ± 1.5 SE, Intent-to-Treat Population, All Patients (N=267) ...9 Table 9.8.1 ARRIVE 1 - Baseline Demographics and Procedural Product Description ....................................................................................2 9.3 Results of the TAXUS I Feasibility Clinical Trial ......................................9 Characteristics ..........................................................................................20 1.1 Device Component Description ...............................................................2 Table 9.3.1 TAXUS I Clinical Results ........................................................9 Table 9.8.2 ARRIVE 1 Principal Safety Results Summary to 2 years 1.2 Drug Component Description ...................................................................2 Figure 9.3.1 TAXUS I Freedom from TVR to 5 Years, Event-Free (N=2487) ......................................................................................................20 1.2.1 Paclitaxel ...................................................................................................2 Survival ± 1.5 SE, Safety population (N=61) ...........................................9 Table 9.8.3 Stent Thrombosis by Time Interval in ARRIVE 1 Figure 1.1 The Chemical Structure of Paclitaxel ..................................2 9.4 TAXUS V – De Novo Expansion Clinical Trial..........................................9 (N=2487) ......................................................................................................20 1.2.2 Translute Polymer Carrier .......................................................................2 Table 9.4.1 TAXUS V de novo Baseline Characteristics ....................10 9.8.2 ARRIVE 2 ...................................................................................................20 Figure 1.2 The Chemical Structure of Translute Polymer Carrier ......2 Table 9.4.2 TAXUS V de novo Clinical Results .....................................10 Table 9.8.4 ARRIVE 2 - Baseline Demographics and Procedural 1.2.3 Product Matrix and Paclitaxel Content ...............................................2 Figure 9.4.1 TAXUS V Freedom from TVR to 5 Years, Event-Free Characteristics ..........................................................................................21 Table 1.2 TAXUS Express2 Stent System Product Matrix and Survival ± 1.5 SE, Safety Population, All Patients (N=1146) ..............10 Table 9.8.5 ARRIVE 2 Principal Safety Results Summary to 2 Years Paclitaxel Content .......................................................................................2 Table 9.4.3 TAXUS V de novo Workhorse Subgroup (N=5005) ......................................................................................................21 2 INTENDED USE/INDICATIONS FOR USE..........................................................3 (one implanted 2.5 mm, 3.0 mm, or 3.5 mm diameter study stent) Table 9.8.6 Stent Thrombosis by Time Interval in ARRIVE 2 Clinical Results ..........................................................................................11 (N=5005) ......................................................................................................21 3 CONTRAINDICATIONS.........................................................................................3 Table 9.4.4 TAXUS V de novo 2.25 mm Diameter Stent Clinical 9.9 Subgroup analysis of the ARRIVE registries ........................................21 4 WARNINGS ............................................................................................................3 Results .........................................................................................................11 Table 9.9.1 Subgroup Outcomes in Pooled ARRIVE 1 and 2 (0-1 5 PRECAUTIONS .......................................................................................................3 Table 9.4.5 Patients with Lesion Length > 26 mm by Visual year) .............................................................................................................21 5.1 General Precautions ...................................................................................3 Estimate and ≥ 2 Planned Stents Clinical Results ..............................11 Table 9.9.2 Subgroup Outcomes in Pooled ARRIVE 1 and 2 (1-2 5.2 Pre-and Post-Procedure Antiplatelet Regimen ....................................3 Table 9.4.6 TAXUS V de novo Large Vessel Sub-Group (4.0 mm years) ...........................................................................................................22 5.2.1 Oral Antiplatelet Therapy ........................................................................3 diameter stent)