1. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2012 Medtronic, Inc. All rights reserved. 10078140DOC_1A 10/2012 Individual and Regional Variations in Dual Antiplatelet Therapy Dose and Duration in a Large, Randomized International Trial Comparing Two Drug-eluting Stents: Results From PROTECT Laura Mauri MD, MSc Brigham and Women’s Hospital, Boston, MA On behalf of P.G. Steg, A. Matteau, E. Camenzind, E. Boersma, P. Vranckx, P.W. Serruys, W.W. O'Neill, R. Yeh, W. Wijns, and the PROTECT Trial Investigators TCT 2012

2. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2012 Medtronic, Inc. All rights reserved. 10078140DOC_1A 10/2012 Background Twelve months’ duration of dual antiplatelet therapy (DAPT) after implantation of a drug-eluting stent (DES) is recommended to decrease risk of stent thrombosis (ST).Twelve months’ duration of dual antiplatelet therapy (DAPT) after implantation of a drug-eluting stent (DES) is recommended to decrease risk of stent thrombosis (ST). Controversies surround the optimal duration of DAPT for reducing risk of thrombosis and whether DAPT should be individualized according to stent type or lesion or patient subsets is unknown.Controversies surround the optimal duration of DAPT for reducing risk of thrombosis and whether DAPT should be individualized according to stent type or lesion or patient subsets is unknown. The PROTECT TrialThe PROTECT Trial is a prospective, multicenter, randomized trial conducted at 196 sites in 36 countries worldwide. Patients with up to 4 coronary lesions amenable for stenting were randomized to receive E-ZES or C-SES. The primary endpoint was ARC definite or probable ST at 3 years, and was recently presented.

3. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2012 Medtronic, Inc. All rights reserved. 10078140DOC_1A 10/2012 Primary Endpoint: Composite of ARC Definite / Probable Stent Thrombosis at 3 years Principle Secondary Endpoints at 3 years: 1.Total Death / Large MI 2.Total Death / Non-Fatal MI 3.Cardiac Death / Large MI 4.Cardiac Death / Non-Fatal MI Endeavor ZES n = 4400 Study Design Largest RCT & First Trial Powered for Comparing ST with DES Initialization Committee: E. Camenzind, G. Steg and W. Wijns Cypher SES n = 4400 Cypher SES n = 4400 6mo4yr3yr30mo18mo24mo12mo Clinical endpoints 5yr30d Real-world patients Single and multiple coronary artery lesions No limitations on number of lesions / vessels N = 8800 1:1 Randomization 196 sites world wide in 5 continents Camenzind E, et al. Am Heart J. 2009;158:902-9

4. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2012 Medtronic, Inc. All rights reserved. 10078140DOC_1A 10/2012 World-Wide Enrolment 8709 Patients from 196 Sites Camenzind E, et al. Am Heart J. 2009;158:902-9 South America 50 pts / 3 sites South America 50 pts / 3 sites US & Canada 230 pts / 19 sites US & Canada 230 pts / 19 sites Europe Western – 3444 pts / 60 sites Central – 1576 pts / 33 sites Southern – 683 pts / 24 sites Eastern – 392 pts / 9 sites Northern – 264 pts / 6 sites Europe Western – 3444 pts / 60 sites Central – 1576 pts / 33 sites Southern – 683 pts / 24 sites Eastern – 392 pts / 9 sites Northern – 264 pts / 6 sites Asia 1245 pts / 19 sites Asia 1245 pts / 19 sites Middle East 326 pts / 7 sites Middle East 326 pts / 7 sites Australia & New Zealand 499 pts / 16 sites Australia & New Zealand 499 pts / 16 sites

5. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2012 Medtronic, Inc. All rights reserved. 10078140DOC_1A 10/2012 Definite / Probable Stent Thrombosis to 3 Yrs Time After Initial Procedure (Years) Cumulative Incidence of ARC Definite / Probable ST 0% 013 5% 2% 2 Patients Entered E-ZES4357434742224119 C-SES4352434442114100 P = 0.224 1% Endeavor ZES (N = 4357) Cypher SES (N = 4352) Primary Endpoint 1.42% 1.79% 3% 4%

6. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2012 Medtronic, Inc. All rights reserved. 10078140DOC_1A 10/2012 DAPT Status at Time of ST Event Number of Definite / Probable ST Events at 3 Years (n) ON DAPT OFF DAPT 61 75 31% ST events with E-ZES were off DAPT, 53% of SES events were off DAPT

7. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2012 Medtronic, Inc. All rights reserved. 10078140DOC_1A 10/2012 Methods of Current Analysis In the PROTECT trial, DAPT with clopidogrel and aspirin were prescribed at least for 3 months and at physician discretion for 12 months or longer. Planned and actual duration of DAPT, utilization of aspirin (ASA) and clopidogrel by region, and aspirin dose ( 300mg) were collected. Individual countries as well as geographical regions were compared: A secondary analysis examined variability between countries with respect to aspirin dosage at time of discharge, in particular ASA 300mg. GeographyCountriesN AmericasArgentina, Canada, Dominican Republic and USA280 Asia PacificAustralia, China, Hong Kong, India, Malaysia, New Zealand, Singapore, South Korea and Taiwan 1744 Eastern Europe and Middle East Czech Rep, Hungary, Israel, Latvia, Poland, Romania and Saudi Arabia 718 Western EuropeAustria, Belgium, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and United Kingdom 5967

8. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2012 Medtronic, Inc. All rights reserved. 10078140DOC_1A 10/2012 Aspirin Dosage by Region 96/280110/1744328/718 2515/ 5967 13/280 1425/ 1744 380/718 3402/ 5967 165/280192/17444/7184/5967 % of Patients Aspirin Dosage More Usage of High Dose ASA in Americas

9. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2012 Medtronic, Inc. All rights reserved. 10078140DOC_1A 10/2012 Usage of Clopidogrel by Country Country< 1 Month>1 – 6 Month> 6 – 12 Month> 12 – 24 Month> 24 – 36 Month Argentina0.0% (0/6) 33.3% (2/6)66.7% (4/6) Australia1.2% (5/414)0.7% (3/414)6.3% (26/414)30.2% (125/414)61.6% (255/414) Austria0.7% (1/144)2.1% (3/144)7.6% (11/144)54.2% (78/144)35.4% (51/144) Belgium2.6% (7/265)7.9% (21/265)21.1% (56/265)32.1% (85/265)36.2% (96/265) Canada3.8% (2/52)0.0% (0/52)5.8% (3/52)42.3% (22/52)48.1% (25/52) China (PRC)0.4% (1/252)0.8% (2/252)4.0% (10/252)63.9% (161/252)31.0% (78/252) Czech Republic10.5% (2/19)15.8% (3/19)47.4% (9/19)26.3% (5/19)0.0% (0/19) Dominican Republic2.3% (1/44)0.0% (0/44) 11.4% (5/44)86.4% (38/44) Finland6.9% (2/29)0.0% (0/29)13.8% (4/29)55.2% (16/29)24.1% (7/29) France1.1% (10/952)3.5% (33/952)7.9% (75/952)30.4% (289/952)57.2% (545/952) Germany2.4% (33/1369)4.3% (59/1369)21.8% (298/1369)56.5% (773/1369)15.0% (206/1369) Greece0.0% (0/55) 1.8% (1/55)27.3% (15/55)70.9% (39/55) Hong Kong3.4% (2/59)1.7% (1/59)15.3% (9/59)66.1% (39/59)13.6% (8/59) Hungary1.9% (2/107)0.0% (0/107) 12.1% (13/107)86.0% (92/107) India1.0% (5/506)1.2% (6/506)1.6% (8/506)6.3% (32/506)89.9% (455/506) Ireland3.0% (1/33) 0.0% (0/33)66.7% (22/33)27.3% (9/33) Israel1.6% (1/64)3.1% (2/64)12.5% (8/64)40.6% (26/64)42.2% (27/64) Italy5.7% (7/123)0.8% (1/123)1.6% (2/123)48.8% (60/123)43.1% (53/123) Korea (South)0.8% (2/254)1.6% (4/254)3.9% (10/254)16.1% (41/254)77.6% (197/254) Latvia2.4% (3/126)4.8% (6/126)50.0% (63/126)33.3% (42/126)9.5% (12/126) Luxembourg0.0% (0/1) 100.0% (1/1) Malaysia5.4% (4/74)2.7% (2/74)8.1% (6/74)33.8% (25/74)50.0% (37/74) Netherlands3.4% (18/535)3.0% (16/535)20.7% (111/535)62.1% (332/535)10.8% (58/535) New Zealand1.2% (1/85)24.7% (21/85)42.4% (36/85)23.5% (20/85)8.2% (7/85) Norway2.9% (1/34)0.0% (0/34)55.9% (19/34)32.4% (11/34)8.8% (3/34) Poland0.0% (0/86)2.3% (2/86)27.9% (24/86)54.7% (47/86)15.1% (13/86) Portugal2.8% (5/177)1.1% (2/177)4.5% (8/177)32.2% (57/177)59.3% (105/177) Romania13.0% (7/54)0.0% (0/54)1.9% (1/54)44.4% (24/54)40.7% (22/54) Saudi Arabia1.5% (4/262)1.9% (5/262) 6.5% (17/262)88.2% (231/262) Singapore0.0% (0/34)2.9% (1/34)8.8% (3/34)82.4% (28/34)5.9% (2/34) Spain1.5% (5/328)0.9% (3/328)8.8% (29/328)52.4% (172/328)36.3% (119/328) Sweden2.0% (4/201) 6.0% (12/201)79.6% (160/201)10.4% (21/201) Switzerland3.2% (2/63)0.0% (0/63)3.2% (2/63)73.0% (46/63)20.6% (13/63) Taiwan0.0% (0/66)6.1% (4/66)43.9% (29/66)24.2% (16/66)25.8% (17/66) United Kingdom1.7% (29/1658)1.9% (31/1658)11.1% (184/1658)74.7% (1239/1658)10.6% (175/1658) United States of America6.2% (11/178)4.5% (8/178)6.7% (12/178)28.1% (50/178)54.5% (97/178)

10. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2012 Medtronic, Inc. All rights reserved. 10078140DOC_1A 10/2012 DAPT Usage to 3 Years Adherence to DAPT (%) Time After Initial Procedure (Months) After 1 Year: Different Practices W. Europe 36121 19.3 47.2 50.6 54.8 246 Americas (N=280) Eastern Europe & Middle East (N=718) Western Europe (N=5967) Asia Pacific (N=1744)

11. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2012 Medtronic, Inc. All rights reserved. 10078140DOC_1A 10/2012 3Yr Definite / Probable ST – Multivariate Analysis Predictors of Stent Thrombosis ITT PopulationOdds RatioP Americas N=280 Asia Pacific N=1744 E.Europe & M.East N=718 Western Europe N=5967 Diabetes1.84 (1.27, 2.67)0.00140.728.842.225.0 Small vessel (RVD ≤ 2.75 mm) 1.66 (1.14, 2.41)0.00847.933.233.642.6 Renal insufficiency2.21 (1.09, 4.48)0.0283.73.03.22.9 History of MI1.61 (1.08, 2.38)0.01817.519.338.219.0 Current smoker1.87 (1.28, 2.73)0.00120.723.928.825.1 Number of stents1.28 (1.11, 1.47)0.0011.5 ± 1.01.5 ± 0.81.6 ± 1.21.7 ± 1.0 Treatment arm was not a predictor in ITT population, even after adjusting number of stents or other variables. None of the interactions between treatment arm and any of the subgroups are significant.

12. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2012 Medtronic, Inc. All rights reserved. 10078140DOC_1A 10/2012 Conclusions (1) 8709 patients were enrolled in PROTECT from 36 different countries.8709 patients were enrolled in PROTECT from 36 different countries. Practice patterns regarding aspirin dose and duration of dual antiplatelet therapy vary markedly across geographic regions within this global randomized trial.Practice patterns regarding aspirin dose and duration of dual antiplatelet therapy vary markedly across geographic regions within this global randomized trial. Use of DAPT beyond 12 months was less common in Western Europe than in other geographies.Use of DAPT beyond 12 months was less common in Western Europe than in other geographies.

13. For OMA distribution only. Trademarks may be registered and are the property of their respective owners. © 2012 Medtronic, Inc. All rights reserved. 10078140DOC_1A 10/2012 Conclusions (2) Use of high dose ASA (>300mg) was more prevalent in North and South America.Use of high dose ASA (>300mg) was more prevalent in North and South America. Geographic variation in DAPT practice patterns is not entirely explained by patient characteristics.Geographic variation in DAPT practice patterns is not entirely explained by patient characteristics. Variation in practice reflects ongoing uncertainty regarding optimal DAPT duration.Variation in practice reflects ongoing uncertainty regarding optimal DAPT duration.