1. For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188271DOC_1A 2/15 Renal Sympathetic Denervation for Treatment of Drug-Resistant Hypertension in an Asian Population: Results from the Global SYMPLICITY Registry in South Korea (GSR Korea) Byeong-Keuk Kim*, Michael Boehm, Felix Mahfoud, Giuseppe Mancia, Sungha Park, Myeong-Ki Hong, Hyo-Soo Kim, Seung-Jung Park, Chang Gyu Park, Ki Bae Seung, Hyeon-Cheol Gwon, Dong-Ju Choi, Tae Hoon Ahn, Chong Jin Kim, Hyuck Moon Kwon, Murray Esler, Yangsoo Jang *Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea

2. For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188271DOC_1A 2/15 Author Disclosures M. Böhm received research support and speaker fees from Medtronic, Inc. and St. Jude Medical. F Mahfoud received speaker honorarium from Medtronic, Inc., St. Jude Medical, and Boston Scientific, and is supported by Deutsche Hochdruckliga and Deutsche Gesellschaft für Kardiologie. G. Mancia is a consultant for Medtronic, Inc. M. Esler received research support, honoraria, and travel support from Medtronic, Inc. All other authors have no conflicts of interest to declare.

3. For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188271DOC_1A 2/15 Abstract Background: Limited clinical reports are available on the response of hypertensive subjects to renal denervation (RDN) in an Asian population. The Global SYMPLICITY Registry (GSR) is a prospective, all-comer, worldwide registry that evaluates the safety and effectiveness of RDN, and includes the Korean registry (GSR Korea). Methods: The aim of the present study was to evaluate 6- and 12-month outcomes after RDN in GSR Korea subjects and to compare their outcomes with those of SYMPLICITY HTN-2, which enrolled a primarily Caucasian population with similar inclusion and exclusion criteria. Results: GSR Korea subjects (N=102) compared with SYMPLICITY HTN-2 subjects (N=89) had lower baseline office SBP (170 ± 15 mm Hg vs. 184 ± 19 mm Hg, respectively, p<0.001), and also lower body mass index, higher estimated glomerular filtration rate, and differences in medications. Subjects in GSR Korea received more radiofrequency ablations during the procedure (15 ± 6 vs. 11 ± 2, p<0.001). Although the 6-month SBP reduction was less in GSR Korea than in HTN-2 there was no difference at 12 months (Figure). In GSR Korea there were no protocol- defined procedure-related adverse events and no chronic adverse events associated with the device.

4. For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188271DOC_1A 2/15 Abstract Conclusions: RDN provided a similar and significant reduction in 12-month SBP of approximately 26 mm Hg in both Asian and Caucasian populations with a favorable safety profile

5. For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188271DOC_1A 2/15 Background Previous studies on renal denervation (RDN) have primarily included Caucasian patients, and reports detailing the response to RDN in Asian patients is limited. Asian patients have on average a smaller body habitus, a lower body mass index (BMI), and different associations between BMI, body fat percentage, and health risks compared to Caucasian populations. It is unclear whether the pathophysiology of resistant hypertension could be different in Asian patients and whether any differences might affect the role of sympathetic tone and consequently RDN results in these patients. The aim of the present analysis was to evaluate 6- and 12-month outcomes after RDN in patients from the Korea substudy treated in the Global SYMPLICITY Registry (GSR) and to compare them to Caucasian patients. While our original analysis compared to Caucasian patients from HTN-2, the current analysis is more robust using a larger sample size of Caucasian patients from GSR who had similar in- and exclusion criteria.

6. For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188271DOC_1A 2/15 Global Symplicity Registry Clinical Trial Design Primary objective: assess peri-procedural and long-term safety of RDN in a real world population Min. 10% randomly assigned to 100% monitoring Key GSR inclusion criteria: any candidate for renal denervation by the Symplicity™ catheter Key GSR-Korea inclusion criteria: office systolic BP ≥160 mmHg (or ≥150 mmHg for diabetes mellitus type-2) while receiving ≥3 antihypertensive medications Key GSR-Korea exclusion criteria: prior renal artery intervention, main renal artery diameter <4mm or length <20mm, hemodynamically or anatomically significant renal artery abnormalities 5000 consecutive “real-world” patients treated with Symplicity™ renal denervation system for uncontrolled hypertension and/or conditions associated with sympathetic nervous system activation 1 Limited to resistant hypertension only Böhm,M, et al. Hypertension. 2015; online ahead of print. doi: 10.1161/HYPERTENSIONAHA.114.05010 GREAT Registry N=1000 Korea Registry 1 N=102 South Africa Registry 1 N=400 Canada & Mexico 1 Rest of GSR N≈3500 Prospective, open-label, single-arm, all-comer observational registry 6M3Y2Y1Y Follow-up 3M4Y5Y 1000 GSR Patients NCT01534299

7. For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188271DOC_1A 2/15 Patient Flowchart

8. For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188271DOC_1A 2/15 Baseline Patient Characteristics % or mean ± SD GSR Korea (N=93) GSR Caucasian (N=169) P-value Office systolic blood pressure, mm Hg168.3 ± 13.9176.1 ± 15.6< 0.001 Office diastolic blood pressure, mm Hg95.5 ± 12.894.5 ± 14.50.403 Age, years55.9 ± 13.461.8 ± 10.8< 0.001 Male gender72.062.70.127 Body mass index, kg/m 2 27.5 ± 4.331.2 ± 5.1< 0.001 Obesity (≥ 30 kg/m 2 )10.838.5< 0.001 Diabetes mellitus type 246.236.30.117 eGFR, ml/min/1.73 m 2 88.9 ± 25.380.9 ± 18.20.011 Renal insufficiency (eGFR <60 ml/min/1.73 m 2 )5.413.60.039 History of atrial fibrillation5.411.30.112 History of sleep apnea2.221.9< 0.001 Heart rate (beats per minute)72.3 ± 11.569.0 ± 14.20.016 Heart failure2.23.0> 0.999

9. For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188271DOC_1A 2/15 Antihypertensive Medications Baseline % (n) GSR Korea (N=93) GSR Caucasian (N=169) P-value No. of anti-hypertensive medication classes3.7 ± 0.94.7 ± 1.2< 0.001 ACE inhibitors8.6 (8)38.5 (65)< 0.001 Angiotensin receptor blockers88.2 (82)69.2 (117)< 0.001 Calcium channel blockers84.9 (79)78.1 (132)0.18 Diuretics83.9 (78)78.1 (132)0.26 Aldosterone antagonists8.6 (8)18.3 (31)0.03 Centrally-acting sympatholytics0.0 (0)43.8 (74)< 0.001 Direct renin inhibitors0.0 (0)12.4 (21)< 0.001 Beta blockers79.6 (74)79.9 (135)0.95 Alpha-adrenergic blocker11.8 (11)37.3 (63)< 0.001 Direct-acting vasodilators4.3 (4)16.6 (28)0.004

10. For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188271DOC_1A 2/15 Antihypertensive Medications 12 Months % (n) GSR Korea (N=93) GSR Caucasian (N=169) P-value No. of anti-hypertensive medication classes3.6 ± 1.14.7 ± 1.3< 0.001 ACE inhibitors6.5 (6)32.1 (54)*< 0.001 Angiotensin receptor blockers90.3 (84)67.9 (114)< 0.001 Calcium channel blockers86.0 (80)77.4 (130)0.09 Diuretics76.3 (71)80.4 (135)0.45 Aldosterone antagonists11.8 (11)28.6 (48)*0.002 Centrally-acting sympatholytics0.0 (0)43.5 (73)< 0.001 Direct renin inhibitors0.0 (0)8.9 (15)0.003 Beta blockers76.3 (71)80.4 (135)0.45 Alpha-adrenergic blocker9.7 (9)34.5 (58)< 0.001 Direct-acting vasodilators6.5 (6)16.7 (28)0.02 * Significant P-value compared to Baseline Note: there were no significant changes to medications at 6 months compared to baseline.

11. For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188271DOC_1A 2/15 Office BP Change 6- and 12 Months

12. For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188271DOC_1A 2/15 Office Systolic BP ≥ 10- and 20 mmHG Reduction

13. For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188271DOC_1A 2/15 Office Systolic BP Distribution Baseline, 6- and 12 Months

14. For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188271DOC_1A 2/15 Office Systolic BP Change Multivariate Analysis 6 Months 6 MonthsEstimate 95% CI p-value Korean (vs Caucasian)-2.4(-7.14, 2.29)0.315 Baseline systolic BP (mmHg)-0.53(-0.68, -0.38)<0.001 Left ventricular hypertrophy7.6(0.60, 14.54)0.034 Calcium channel blockers7.1(1.51, 12.65)0.013 12 Months 12 MonthsEstimate 95% CI p-value Korean (vs Caucasian)-11.8(-16.85, -6.73)<0.001 Baseline systolic BP (mmHg)-0.73(-0.88, -0.58)<0.001 Alpha-adrenergic blocker6.1(0.80, 11.36)0.025

15. For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188271DOC_1A 2/15 Safety Outcomes at 12 Months % GSR Korea (n = 93/93) GSR Caucasian (n=165/169) P-value Procedure-related vascular complications 0.00.0 13 Death 0.00.0 23 Spontaneous myocardial infarction0.00.61.00 Serum creatinine elevation > 50%0.00.0 13 Renal failure 1.10.00.36 Atrial fibrillation requiring hospitalization 2.20.60.29 Stroke 2.20.60.29 Hypertensive crisis requiring hospitalization 1.11.21.00 Vascular complication 0.01.20.54 1 For vascular complications and serum creatinine elevation >50%, 12-month data available on all 169 matched patients 2 There was no deaths in the total GSR population (N=432) 3 P-value cannot be calculated when there are no events in both arms

16. For OMA distribution only. Trademarks may be registered and are the property of their respective owners © 2015 Medtronic, Inc. All Rights Reserved. 10188271DOC_1A 2/15 Conclusions RDN in the GSR Korea substudy provided a significant reduction in office systolic BP at 6 and 12 months compared to baseline. As compared to the GSR Caucasian subset, the reduction in systolic BP in GSR Korea was similar at 6 months but higher at 12 months, despite fewer baseline medications and a lower baseline systolic BP in Korean patients; contrary to prior studies that consistently indicated a relationship between baseline systolic BP and RDN BP-lowering response. In multivariate analysis that adjusted for baseline differences, Korean patients remained more likely to have a larger reduction in 12-month systolic BP Sympathetic tone might play a larger role in the pathogenesis of hypertension in Asian patients compared to Caucasian patients, thus producing a larger decrease in SBP by RDN in this ethnic group. Finally, RDN with the Symplicity™ catheter showed favorable safety results.