All Comers DES Trials Industry View Rick Kuntz

Study Purpose • Pre Market: Proof of principle with a focus on impact of

Historical Perspective DES Pivotal Trials Baseline Characteristics DES Arms ENDEAVOR II N = 598

Historical Perspective DES Pivotal Trials Clinical Outcomes at 12 Months ENDEAVOR II 1 N

Historical Perspective DES Pivotal Trials Clinical Outcomes at 5 Years ENDEAVOR II 1 N

RESOLUTE Global Clinical Program In Follow Up / Enrolling RESOLUTE 1, 2, 3 RESOLUTE

Resolute Clinical Program • Both All Comers populations – R-AC: 100% monitored RCT •

RESOLUTE All Comers Patient Eligibility Inclusion Criteria Coronary artery disease • Stable angina •

RESOLUTE All Comers Baseline Characteristics Resolute ZES (N = 1140) Xience V EES (N

RESOLUTE International Patient Eligibility Inclusion Criteria Coronary artery disease • Stable angina • Silent

RESOLUTE International Baseline Characteristics (N = 2349) Age (yr) 63. 5 ± 11. 2

RESOLUTE International Comparison with RESOLUTE All Comers at 12 Months Age Male Diabetics ACS

RESOLUTE International Comparison with RESOLUTE All Comers at 12 Months RESOLUTE All Comers Resolute

Pre Approval versus All Comers Outcomes Different results due to patient populations included or

Conclusion • Meaningful clinical trials that both achieve approval and advance the understanding on

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Study Purpose • Pre Market: Proof of principle with a focus on impact of product on clinical outcomes, minimize the impact of potential confounding variables. Challenging to enroll rapidly due to extensive exclusion criteria • Post Market (all comers): Provides surveillance opportunity with a focus on understanding actual use indications, results in new reference populations, and improvements in statistical confidence in rates of known endpoints. Limitations on determining new outcomes due to multiplicity concerns however does provide useful evidence for current practice • The all comers format is valuable but needs improved scalability to remain feasible and efficient.

Historical Perspective DES Pivotal Trials Baseline Characteristics DES Arms ENDEAVOR II N = 598 SIRIUS N = 533 TAXUS IV N=662 SPIRIT III N = 669 RVD (mm) 2. 74 2. 78 2. 75 2. 77 Lesion Length (mm) 14. 0 14. 4 13. 4 14. 7 Stent: Lesion Length 1. 84 1. 40 1. 58 1. 6 B 2/C Lesions (%) 78. 4 58. 6 50. 8 n/a Diabetes Mellitus (%) 18. 2 25. 0 24. 4 29. 6 LAD (%) 43 44 40 41 Plavix/Ticlid LOT (m) 3 3 6 6 mo yes no no no Inclusion 2. 25 vessels Extensive exclusion criteria: AMI, LM, SVG, bifurcation lesions etc

Historical Perspective DES Pivotal Trials Clinical Outcomes at 12 Months ENDEAVOR II 1 N = 598 SIRIUS 2 N = 533 TAXUS IV 3 SPIRIT III 4 N=662 N = 669 TVF* 10. 0 9. 8 9. 7** 8. 6 MACE* 8. 8 8. 3 11. 2 6. 0 ID TLR 5. 9 4. 3 3. 4 CD/TVMI 1. 0 4. 3 (D/MI) n/a 3. 4 (CD/MI 3. 7 (D/MI) TVMI 2. 7 3. 0 (all MI) 3. 6 (all MI) 2. 8 ARC Def/Prob ST 0. 7 0. 4 0. 8 Cardiac Death 1. 0 0. 6 1. 4 0. 8 Death 1. 4 1. 3 2. 4 1. 2 * Endpoint definitions differ between trials **at 9 mths 1 3 Fajadet J, et al. Euro. Intervention. 2010; 6: 562 -7. 2 Weisz G, et al. JACC. 2009; 53: 1488 -97. Ellis S, et al. JACC. 2009; 2: 1248 -59. 4 Stone G, et al. JANA. 2008; 299(16): 1903 -13.

Historical Perspective DES Pivotal Trials Clinical Outcomes at 5 Years ENDEAVOR II 1 N = 598 SIRIUS 2 N = 533 TVF* 15. 4 22. 5 n/a MACE* 15. 4 20. 3 24. 0 n/a ID TLR 7. 5 9. 4 9. 1 n/a CD/TVMI 6. 6 13. 9 (D/MI) n/a TVMI 3. 8 6. 2 (all MI) 7. 2 (all MI) n/a ARC Def/Prob ST 0. 9 1. 2 2. 2 n/a 3. 1 4. 4 n/a 6. 2 8. 4 10. 0 n/a Cardiac Death TAXUS IV 3 SPIRIT III 4 N=662 N = 669 * Endpoint definitions differ between trials 1 3 Fajadet J, et al. Euro. Intervention. 2010; 6: 562 -7. 2 Weisz G, et al. JACC. 2009; 53: 1488 -97. Ellis S, et al. JACC. 2009; 2: 1248 -59. 4 Stone G, et al. JANA. 2008; 299(16): 1903 -13.

RESOLUTE Global Clinical Program In Follow Up / Enrolling RESOLUTE 1, 2, 3 RESOLUTE AC 4 RESOLUTE Intl RESOLUTE US Non-RCT First-in-Human (Resolute=139) 4 yr 1: 1 RCT vs. Xience DES (Resolute=1150; Xience V=1150) 1 yr Open Label Real World (Resolute=2200) 1 yr 2. 25 – 3. 5 mm Non-RCT vs. Hx Control (Resolute=1241) 6 mo 2. 25 – 3. 5 mm Angio/IVUS Non-RCT vs. Hx Control (R=100) 6 mo 4. 0 mm Angio Non-RCT vs. Hx Control (Resolute=58) 6 mo 38 mm sub-study Non-RCT vs. PG (Resolute=110 -175) RESOLUTE Japan SVS RESOLUTE Asia 2. 5 – 3. 5 mm Non-RCT (Resolute=100) vs. Hx Control enroll 6 mo 2. 25 Non-RCT vs. Performance Goal (Resolute≈60) enroll plan Open Label Real World (Resolute= 249 -411) enroll 1 Meredith IT, et al. Euro. Intervention. 2010; 5: 692 -7 IT, et al. J Am Coll Cardiol Intv. 2009; 2: 977 -85 3 Meredith IT, et al. Euro. Intervention. 2007; 3: 50 -53 4 Serruys PW, et al. N Engl J Med. 2010; 363: 136 -46 2 Meredith CAUTION: Resolute DES is an investigational product. Limited by Federal (United States) law to investigational use. For OMA distribution only © 2011 Medtronic, Inc. All rights reserved. 10013259 DOC 2/2011

Resolute Clinical Program • Both All Comers populations – R-AC: 100% monitored RCT • Small # of site in on geography – R-Int: 25% monitored register • Large # of sites in many countries CAUTION: Resolute DES is an investigational product. Limited by Federal (United States) law to investigational use. For OMA distribution only © 2011 Medtronic, Inc. All rights reserved. 10013259 DOC 2/2011

RESOLUTE All Comers Patient Eligibility Inclusion Criteria Coronary artery disease • Stable angina • Silent ischemia • Acute coronary syndrome including UA, NSTEMI and STEMI Lesion characteristics • Number of lesions : no limitation • Number of vessels : no limitation • Lesion length : no limitation Written informed consent Exclusion Criteria Known intolerance to Aspirin, clopidogrel, heparin, cobalt alloy, everolimus, zotarolimus, contrast material, polymer coating Planned, elective surgery within 6 months of PCI Unless dual anti-platelet therapy could be maintained Pregnancy Participation in another trial Serruys PW, et al. , N Engl J Med. 2010; 363(2): 136 -46 CAUTION: Resolute DES is an investigational product. Limited by Federal (United States) law to investigational use. For OMA distribution only © 2011 Medtronic, Inc. All rights reserved. 10013259 DOC 2/2011

RESOLUTE All Comers Baseline Characteristics Resolute ZES (N = 1140) Xience V EES (N = 1152) P value Age (yr) 64. 4 ± 10. 9 64. 2 ± 10. 8 0. 70 Men (%) 76. 7 77. 2 0. 80 Diabetes mellitus (%) 23. 5 23. 4 1. 00 8. 4 7. 1 0. 28 ACS (%) 48. 3 47. 7 0. 80 AMI (within 12 hr) (%) 15. 4 17. 8 0. 13 AMI (within 72 hr) (%) 28. 9 28. 8 0. 96 Multivessel disease (%) 58. 4 59. 2 0. 73 Small vessel (RVD ≤ 2. 75 mm) 67. 8 67. 4 0. 88 Long lesion (length >18 mm) 18. 2 21. 2 0. 11 Bifurcation/trifurcation (%) 16. 9 17. 7 0. 62 Total occlusion (%) 16. 3 17. 2 0. 61 In-stent restenosis (%) 8. 1 8. 0 0. 94 Complex Patients 1 (%) 67. 0 65. 6 0. 51 IDDM 1 Complex patient definition: bifurcation, bypass grafts, ISR, AMI <72 hr, LVEF <30%, unprotected LM, >2 vessels stented, renal insufficiency or failure (creatinine >140 µmol/L), lesion length >27 mm, >1 lesion per vessel, lesion with thrombus or TO (preprocedure TIMI = 0). Serruys PW, Silber S, et al. , N Engl J Med. 2010; 363(2): 136 -46 CAUTION: Resolute DES is an investigational product. Limited by Federal (United States) law to investigational use. For OMA distribution only © 2011 Medtronic, Inc. All rights reserved. 10013259 DOC 2/2011

RESOLUTE International Patient Eligibility Inclusion Criteria Coronary artery disease • Stable angina • Silent ischemia • Acute coronary syndrome including UA, NSTEMI and STEMI Intention to electively implant at least one Resolute stent Exclusion Criteria Pregnancy Inability to comply with follow-up requirements Participation in another trial Lesion characteristics • Number of lesions: no limitation • Number of vessels: no limitation • Lesion length: no limitation Written informed consent Belardi J. TCT 2010 CAUTION: Resolute DES is an investigational product. Limited by Federal (United States) law to investigational use. For OMA distribution only © 2011 Medtronic, Inc. All rights reserved. 10013259 DOC 2/2011

RESOLUTE International Baseline Characteristics (N = 2349) Age (yr) 63. 5 ± 11. 2 Men (%) 77. 8 Diabetes mellitus (%) 30. 5 IDDM 9. 0 ACS (%) 46. 0 AMI (within 12 hr) (%) 9. 7 AMI (within 72 hr) (%) 20. 0 Multi vessels treated (%) 14. 0 Small vessel (RVD ≤ 2. 75 mm) 45. 4 Long lesion (length >18 mm) 46. 1 Bifurcation/trifurcation (%) 21. 8 Chronic Total occlusion (%) 7. 9 In-stent restenosis (%) 8. 1 Complex Patients 1 (%) 67. 5 1 Complex patient definition: bifurcation, bypass grafts, ISR, AMI <72 hr, LVEF <30%, unprotected LM, >2 vessels stented, renal insufficiency or failure (creatinine >140 µmol/L), lesion length >27 mm, >1 lesion per vessel, lesion with thrombus or TO (preprocedure TIMI = 0). Serruys PW, Silber S, et al. , N Engl J Med. 2010; 363(2): 136 -46 CAUTION: Resolute DES is an investigational product. Limited by Federal (United States) law to investigational use. For OMA distribution only © 2011 Medtronic, Inc. All rights reserved. 10013259 DOC 2/2011

RESOLUTE International Comparison with RESOLUTE All Comers at 12 Months Age Male Diabetics ACS (Acute MI (<72 h) or unstable angina) Complex patients R-All Comers R-International 48. 3 % 46. 1 % 67. 0 % 67. 5 % Randomized Resolute arm N = 1140 64. 4 ± 10. 9 y 76. 7 % 23. 5 % Single arm All patients N = 2349 63. 5 ± 11. 2 y 77. 8 % 30. 5 % CAUTION: Resolute DES is an investigational product. Limited by Federal (United States) law to investigational use. For OMA distribution only © 2011 Medtronic, Inc. All rights reserved. 10013259 DOC 2/2011

RESOLUTE International Comparison with RESOLUTE All Comers at 12 Months RESOLUTE All Comers Resolute arm (N = 1140) RESOLUTE International (N = 2349) 8. 7 8. 2 8. 0 Percentage [%] 6. 9 5. 4 3. 9 4. 2 3. 4 4. 2 3. 1 2. 3 1. 6 0. 9 TLF MACE TLR C. Death / TVMI ARC ST Def/Prob 1. 3 C. Death 1. 6 Death Similar outcomes despite design differences: lower adverse event rate in R-Int due to lower peri-procedural MI’s (no measurement of CKMB mandated) CAUTION: Resolute DES is an investigational product. Limited by Federal (United States) law to investigational use. For OMA distribution only © 2011 Medtronic, Inc. All rights reserved. 10013259 DOC 2/2011

Pre Approval versus All Comers Outcomes Different results due to patient populations included or improving technology or better techniques? CAUTION: Resolute DES is an investigational product. Limited by Federal (United States) law to investigational use. For OMA distribution only © 2011 Medtronic, Inc. All rights reserved. 10013259 DOC 2/2011

Conclusion • Meaningful clinical trials that both achieve approval and advance the understanding on use and outcomes for all patients currently treated by PCI are the goals of industry providers • Initial proof-of-principal trials are generally simpler homogenous samples, limited inference to broader reference populations, but have high validity. • All Comers trials have improved ease-of-execution, are scalable and efficient, and extend initial pivotal trial results to create new data on diverse subjects whose actual use indications and results may be contrasted. • All Comers studies provide helpful contrasts and are subject to multiplicity type I error for direct conclusions about individual subsets CAUTION: Resolute DES is an investigational product. Limited by Federal (United States) law to investigational use. For OMA distribution only © 2011 Medtronic, Inc. All rights reserved. 10013259 DOC 2/2011

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