Jeffrey J. Popma, MD Director, Cardiac Catheterization Laboratory St. Elizabeth Medical Center Research Associate Harvar

2. The Endeavor DES System Key Points Each of the Endeavor stent’s design elements contributes to its unique performance. The overall effect of the Endeavor DES’ design is to allow rapid and complete healing of the endothelium. The Endeavor DES system consists of four components1 [Medtronic website/p 1] The proven Driver® coronary stent platform An advanced stent delivery system A biocompatible polymer that mimics red blood cell chemistry A drug—zotarolimus—that is a potent, lipophilic, antiproliferative agent that elutes completely from the stent and maintains effective tissue concentrations through 28 days Reference 1. Medtronic, Inc. Different by design. Available at: www.endeavorstent.com/wt/tertiary/en_endeavorsprint_differentbydesign.html. Accessed January 25, 2008. Key Points Each of the Endeavor stent’s design elements contributes to its unique performance. The overall effect of the Endeavor DES’ design is to allow rapid and complete healing of the endothelium. The Endeavor DES system consists of four components1 [Medtronic website/p 1] The proven Driver® coronary stent platform An advanced stent delivery system A biocompatible polymer that mimics red blood cell chemistry A drug—zotarolimus—that is a potent, lipophilic, antiproliferative agent that elutes completely from the stent and maintains effective tissue concentrations through 28 days Reference 1. Medtronic, Inc. Different by design. Available at: www.endeavorstent.com/wt/tertiary/en_endeavorsprint_differentbydesign.html. Accessed January 25, 2008.

3. Polymer Safety

5. Medtronic Polymer TechnologiesPC and BioLinx Polymers Hydrophilic Surface

6. Polymer Safety

9. Polymer Safety

13. It is A Debate – So Be Bold “Using the Endeavor Stent in Non Complex Lesions Will Result in Lower Rates of TLR AND Lower Rates of Death and MI Than a Bare Metal Stent three years after the procedure” It Cannot Get Better Than This

14. Log Rank P value 0.0002Log Rank P value 0.0002

15. In the Beginning – Efficacy Was The Only Concern

16. TCT:2006: Independent CRF patient-level meta-analysis Freedom From (Protocol) Stent Thrombosis

17. SIRIUS – Clinical Events @ 5 yrs This is the Sample Column Chart slide. To create this particular slide, copy and paste the sample in the Slide Sorter view as follows: Select View / Slide Sorter Highlight the Sample Column Chart page and select Edit / Copy Place the courser where you want the new slide to be and select Edit / Paste Double-click on the pasted-in slide to return to Slide view To access the column chart, right/click on the chart and select chart object / open from the menu. This will open the chart in Microsoft Graph. You can make any changes to the chart and spreadsheet here. When you are finished making your changes, select File / Exit and return to… from the menu bar. THIS METHOD IS PREFERRED TO DOUBLE-CLICKING THE GRAPH AND OPENING IT IN POWERPOINT. Double-clicking the graph can sometimes reformat the sizes, colors, animations and fonts in your graph. This is the Sample Column Chart slide. To create this particular slide, copy and paste the sample in the Slide Sorter view as follows: Select View / Slide Sorter Highlight the Sample Column Chart page and select Edit / Copy Place the courser where you want the new slide to be and select Edit / Paste Double-click on the pasted-in slide to return to Slide view To access the column chart, right/click on the chart and select chart object / open from the menu. This will open the chart in Microsoft Graph. You can make any changes to the chart and spreadsheet here. When you are finished making your changes, select File / Exit and return to… from the menu bar. THIS METHOD IS PREFERRED TO DOUBLE-CLICKING THE GRAPH AND OPENING IT IN POWERPOINT. Double-clicking the graph can sometimes reformat the sizes, colors, animations and fonts in your graph.

22. Key Point The ENDEAVOR clinical trial program is a large and robust program that evaluated the efficacy and safety of Endeavor DES in patients with single de novo native coronary artery lesions. This slide summarizes the ENDEAVOR clinical program, which evaluated the safety and efficacy of Endeavor DES in patients with single de novo native coronary artery lesion. The ENDEAVOR II trial compared Endeavor DES with BMS, while ENDEAVOR III and IV trials assessed the stent versus currently approved DES, Taxus and Cypher. The ENDEAVOR II and IV trials were designed with the primary endpoint of total vessel failure, assessed by quantitative coronary angiography (QCA) and by IVUS in a subset of patients. The primary endpoint in ENDEAVOR III was in-segment late lumen loss, assessed by QCA at 8 months. All three trials required at least 3 months of dual antiplatelet therapy, the duration of which was extended to at least 6 months in ENDEAVOR IV. Key Point The ENDEAVOR clinical trial program is a large and robust program that evaluated the efficacy and safety of Endeavor DES in patients with single de novo native coronary artery lesions. This slide summarizes the ENDEAVOR clinical program, which evaluated the safety and efficacy of Endeavor DES in patients with single de novo native coronary artery lesion. The ENDEAVOR II trial compared Endeavor DES with BMS, while ENDEAVOR III and IV trials assessed the stent versus currently approved DES, Taxus and Cypher. The ENDEAVOR II and IV trials were designed with the primary endpoint of total vessel failure, assessed by quantitative coronary angiography (QCA) and by IVUS in a subset of patients. The primary endpoint in ENDEAVOR III was in-segment late lumen loss, assessed by QCA at 8 months. All three trials required at least 3 months of dual antiplatelet therapy, the duration of which was extended to at least 6 months in ENDEAVOR IV.

23. ENDEAVOR Clinical Program Key Points The percentage of patients who remain on dual antiplatelet therapy declines across time. At day 0 of follow-up, nearly all patients (>97%) were taking dual antiplatelet therapy. The percentage of patients who remained on dual antiplatelet therapy declined across time; by 9-month follow-up, 56% of patients enrolled in the ENDEAVOR II Continued Access (CA) registry were taking dual antiplatelet therapy. In contrast, the percentage of patients who remained on dual antiplatelet therapy in ENDEAVOR II, III, and IV ranged from 65% to 92%.1 Reference Medtronic, Inc. Data on file. Key Points The percentage of patients who remain on dual antiplatelet therapy declines across time. At day 0 of follow-up, nearly all patients (>97%) were taking dual antiplatelet therapy. The percentage of patients who remained on dual antiplatelet therapy declined across time; by 9-month follow-up, 56% of patients enrolled in the ENDEAVOR II Continued Access (CA) registry were taking dual antiplatelet therapy. In contrast, the percentage of patients who remained on dual antiplatelet therapy in ENDEAVOR II, III, and IV ranged from 65% to 92%.1 Reference Medtronic, Inc. Data on file.

24. Endeavor Reduces Restenosis in Non Complex Lesions Compared with Bare Metal Stents Endeavor Provides Equivalent Clinical Outcomes in Non Complex Lesions Compared with TAXUS Universal Agreement

25. EII: Simple Lesion Length Subset AnalysisTarget Lesion Revascularization to 270 Days

26. Key Points In the ENDEAVOR IV Trial, which had both angiographic and nonangiographic cohorts, the rate of TLR is lower in the clinical cohort. The “oculostenotic” reflex—the instinct to treat a vessel that shows any visible stenosis during invasive follow-up—may drive these higher rates of TLR in the angiographic cohorts versus the clinical cohorts. Among patients who underwent angiographic follow-up (141 Endeavor DES and 133 Taxus DES patients), 8.5% and 3.0% of those who received the Endeavor DES and Taxus DES, respectively, subsequently underwent TLR (P = .070).1 [Leon 2007/slide 40] In contrast, among patients who underwent only clinical follow up (608 Endeavor DES and 608 Taxus DES patients), 3.6% and 3.3% of those who received the Endeavor DES and Taxus DES, respectively, subsequently underwent revascularization (P = .875).1 [Leon 2007/slide 40] Reference 1. Leon MB. Endeavor IV: a randomized comparison of a zotarolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease. Presented at: Annual Meeting of Transcatheter Cardiovascular Therapeutics; October 20-25, 2007; Washington, DC.Key Points In the ENDEAVOR IV Trial, which had both angiographic and nonangiographic cohorts, the rate of TLR is lower in the clinical cohort. The “oculostenotic” reflex—the instinct to treat a vessel that shows any visible stenosis during invasive follow-up—may drive these higher rates of TLR in the angiographic cohorts versus the clinical cohorts. Among patients who underwent angiographic follow-up (141 Endeavor DES and 133 Taxus DES patients), 8.5% and 3.0% of those who received the Endeavor DES and Taxus DES, respectively, subsequently underwent TLR (P = .070).1 [Leon 2007/slide 40] In contrast, among patients who underwent only clinical follow up (608 Endeavor DES and 608 Taxus DES patients), 3.6% and 3.3% of those who received the Endeavor DES and Taxus DES, respectively, subsequently underwent revascularization (P = .875).1 [Leon 2007/slide 40] Reference 1. Leon MB. Endeavor IV: a randomized comparison of a zotarolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease. Presented at: Annual Meeting of Transcatheter Cardiovascular Therapeutics; October 20-25, 2007; Washington, DC.

30. Log Rank P value 0.053Log Rank P value 0.053

31. Log Rank P value 0.07Log Rank P value 0.07

33. The Endeavor Stent Reduces Restenosis by >50% Compared with Bare Metal Stents and Comparably to the TAXUS Stent in non complex lesions ? Less Early Death MI Endeavor Has Comparable (or Lower) Rates of Very Late Stent Thrombosis as a Bare Metal Stent ? Equivalent Death - MI It is A Debate But the Answer is Clear

34. Log Rank P value 0.0002Log Rank P value 0.0002