Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. SYMPLICITY HTN-3 Trial: 12-month outcomes following un-blinding of subjects at 6 months Overview of Presentations given by: Dr. George Bakris at ESC 2014 & Deepak Bhatt at TCT 2014

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. Background SYMPLICITY HTN-3 is the first randomized, blinded, sham-controlled clinical trial of renal denervation for treatment-resistant hypertension. Initial results confirmed the safety of renal denervation but did not achieve the 6-month primary efficacy endpoint.

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. 6-Month Primary Efficacy Endpoint *P value for superiority with a 5 mm Hg margin bars denote standard deviations

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. We now present the 12 month data of available patients Home BP & HTN med confirmation Office SBP ≥160 mm Hg Full doses ≥3 meds No med changes in past 2 weeks No planned med changes for 6 mo Screening Visit 1 Home BP & HTN med confirmation Home BP & HTN med confirmation Primary endpoint 2 weeks 1M 3M 6M6M 6M M Patients, BP assessors, and study personnel all blinded to treatment status No changes in medications for 6 months 2 weeks Renal angiogram; Eligible subjects randomized Sham Procedure Renal Denervation Office SBP ≥160 mm Hg 24-h ABPM SBP ≥135 mm Hg Documented med adherence Screening Visit 2 Cross- over 2:1 randomization, blinded and sham controlled 535 subjects randomized out of 1441 enrolled at 88 sites in US Trial Design Bhatt DL, Kandzari DE, et al...Bakris GL N Engl J Med. 2014;370:

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. Methods All clinicians and subjects were un-blinded to randomization following the primary 6-month endpoint evaluation. Sham control subjects were allowed to cross over to RDN following the 6-month primary endpoint evaluation if they continued to satisfy study inclusion and exclusion criteria. Follow up of the study cohort will continue for up to 5 years.

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. Patient Disposition: 6 Months to 1 Year 322 Subjects (91%) 12M follow-up 4 died 3 withdrew 354 eligible for 12M follow-up Crossover 101 Subjects Non-Crossover 70 Subjects 2 died 6 withdrew 2 died 3 withdrew 96 eligible for 6M post-RDN follow-up 93 Subjects (96.9%) 6M post-RDN follow-up Sham-Control group 171 Subjects Denervation group 361 Subjects 62 eligible for 12M follow-up 48 Subjects (77%) 12M follow-up Crossover subjects were denervated after unblinding at 6 months if blood pressure criteria for treatment were met and subjects elected to proceed.

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. Baseline Population Demographics Denervation n=364 Crossover n=101 Non-Crossover n=70 Age (years)58 ± 1055 ± 1158 ± 12 Male sex (%) Office systolic blood pressure (mm Hg)180 ± ± ± hour mean systolic ABPM (mm Hg)159 ± ± ± 15 BMI (kg/m 2 )34.2 ± ± ± 7.8 Race (%) White Black or African American Medical history (%) Renal insufficiency (eGFR <60ml/min/1.73m 2 ) Renal artery stenosis Obstructive sleep apnea Stroke Type 2 diabetes Hypertensive crisis Hyperlipidemia Current smoking Prescribed anti-hypertensive drugs >10 years

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. Prescribed Antihypertensive Medications Denervation n=364 Crossover n=101 Non-Crossover n=70 Baseline5.1 ± ± ± months5.0 ± ± ± months5.0 ± 1.6n/a4.9 ± 1.5

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. Safety to 12 Months Denervation n=364 Crossover* n=101 Non-Crossover n=70 To 6 Months Composite Safety to 6M (%) 3.6 (13/358)5.2 (5/96)2.9 (2/70) Death New-onset end-stage renal disease0.0 Sig. embolic event resulting in end-organ damage Vascular complication Renal artery re-intervention0.0 Hypertensive crisis/emergency New renal artery stenosis >70%0.0 To 12 Months Composite Safety to 12M (%) 6.8 (24/355)n/a7.2 (5/69) Death1.8n/a3.6 New-onset end-stage renal disease0.3n/a0.0 Sig. embolic event resulting in end-organ damage0.3n/a0.0 Vascular complication0.3n/a0.0 Renal artery re-intervention0.6n/a0.0 Hypertensive crisis/emergency4.8n/a5.5 *Safety from time of crossover procedure

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. Procedural Details Denervation n=364 Crossover n=101 Non-Crossover n=70 Procedure time (min)93 ± 3876 ± 3056 ± 33 Denervation time (min)46 ± 1543 ± 12n/a Contrast volume (ml)177 ± ± 6081 ± 50 Treatment attempts11.2 ± ± 2.4n/a Full 120-second treatments9.2 ± ± 1.9n/a Hospital stay (days)1.0 ± ± ± 0.6

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. Medication Changes to 12 Months

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. Change in Office Blood Pressure through 12- Months Post-Procedure Baseline SBP (mm Hg) * Baseline DBP (mm Hg) * Note: BP changes are vs. patient baseline, not RDN – Control *Baseline = time of RDN procedure P=0.025 for SBP difference

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. Change in Office Blood Pressure through 12- Months Post-Procedure Baseline SBP (mm Hg)176 Baseline DBP (mm Hg)94 Note: BP changes are vs. patient baseline, not RDN – Control

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. Change in 24-h Ambulatory Blood Pressure at 6 and 12 Months for Denervation Subjects *Baseline = time of RDN procedure Note: BP changes are vs. patient baseline, not RDN vs Control. Error Bars = 1.96SE Baseline SBP (mm Hg) Baseline DBP (mm Hg)

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. Note: BP changes are vs. patient baseline, not RDN – Control Baseline SBP (mm Hg)151 Baseline DBP (mm Hg)86 Change in 24-h Ambulatory Blood Pressure at 6 and 12 Months for Non-Crossover Subjects

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. Relationship Between Office SBP Changes and Number of Ablations Attempted for Combined* RDN Subjects at 6 Months *Denervation and crossover subjects combined

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. Relationship Between 24-Hr Ambulatory SBP Changes and Number of Ablations Attempted for Combined* RDN Subjects at 6 Months *Denervation and crossover subjects combined

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. Systolic Blood Pressure Change at 6 Months According to Ablation Pattern Four quadrants = 1 superior, 1 inferior, and 2 posterior

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. Limitations All patients and clinicians were un-blinded at 6 months. Disposition of the original sham control group patients after 6 months was determined by eligibility and patient choice and not randomized. Most non-crossover patients had controlled office blood pressure at 6 months and thus were not eligible for crossover.

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14. Conclusions Renal denervation with the Symplicity™ system was safe with no difference in major adverse events between the treated and original sham procedure groups out to 12 months post procedure. Patients in the original therapy group, patients who crossed over at 6 months, and patients who did not cross over all show consistent reductions in office and ambulatory blood pressure 12 months post randomization. Possible confounding factors including the population studied, drug prescription changes, variable adherence to therapy and procedural variability all remain unresolved at 12 months. Thus, further research is needed.

Trademarks may be registered and are the property of their respective owners. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. CAUTION: The Symplicity Renal Denervation System is an investigational device in the United States, limited by Federal (or United States) law to investigational use. Not for distribution in the USA, Japan or France.© 2014 Medtronic, Inc. All rights reserved. UC aML 9/14.