Medtronic RDN Global Symplicity Registry (GSR)

Trademarks may be registered and are the property of their respective owners. A reminder that this is a discussion of SYMPLICITY trial results and their implications for the future of RDN. Today’s discussion may regard information or indications not evaluated by regulatory authorities in your geography. Always refer to the Instructions for Use prior to using the Symplicity renal denervation system. Investigational use only in the USA © 2014 Medtronic, Inc. All rights reservedUC201406133IE 3/14

Medtronic RDNGlobal Symplicity Registry (GSR)


Key Takeaways

• Six-month results confirm the procedural safety with the SymplicityTM

system in the largest real-world population studied.

• The SymplicityTM system significantly reduced both office and

ambulatory BP from baseline.

• It will be important to reconcile the results from this real-world registry

with those of SYMPLICITY HTN-3, which included randomization,

blinding, sham control, BP inclusion criteria, antihypertensive-drug

treatment intensity, and an African American cohort.


6M 3Y2Y1YFollow-up schedule 3M 4Y 5Y

* Limited to resistant hypertension only

231 international sites in 37 countriesMin. 10% randomly assigned to 100% monitoring

Global Symplicity Registry (GSR)

Consecutive patients treated in real-world population

5000 patients

GREAT RegistryN = 1000

Korea Registry*N = 102

South Africa Registry*N = 400

Canada and Mexico*

Rest of GSRN ≈ 3500


Patient Disposition


All Patients(N = 1000)

SBP ≥160 mm Hg and Ambulatory SBP ≥135* mm Hg

(N = 327)

Gender (% male) 61.2% 63.9%

Age (years) 60.7 ± 12.0 61.0 ± 10.9

BMI (kg/m2) 30.5 ± 5.5 30.9 ± 5.5

Current smoking 10.0% 11.0%

History of cardiac disease 50.5% 52.9%

Renal impairment (eGFR <60 mL/min/1.73 m2)

23.4% 27.9%

Sleep apnea (AHI≥5) 4.2% 5.9%

Diabetes, type 1 3.2% 2.5%

Diabetes, type 2 38.5% 42.6%

1 comorbidity 39.7% 36.7%

2 comorbidities 35.5% 34.6%

3+ comorbidities 24.6% 28.4%

* With ≥3 antihypertensive medication classes

Baseline Patient Characteristics


All Patients(N = 1000)

SBP ≥160 mm Hg and Ambulatory SBP ≥135 mm Hg*

(N = 327)

Antihypertensive medication class 4.5 ± 1.3 4.7 ± 1.2

Beta-blockers 78.9% 81.0%

ACE inhibitors 33.8% 38.5%

Angiotensin receptor blockers 67.3% 67.9%

Calcium channel blockers 76.3% 78.9%

Diuretics 78.2% 79.8%

Aldosterone antagonists 21.1% 19.3%

Spironolactone 18.6% 15.9%

Alpha-adrenergic blockers 35.2% 40.1%

Direct-acting vasodilators 15.1% 19.0%

Centrally acting sympatholytics 33.2% 37.6%

Direct renin inhibitor 7.4% 7.7%

Antihypertensive Medication Use

*With ≥3 antihypertensive medication classes.


HTN-3 RDN Arm(N = 364)

GSR All Patients(N = 1000)

GSR Office SBP ≥160 mm Hgand ABPM ≥ 135* mm Hg

(N=327)

MAE 1.4% 0.8% 1.3%

At 6 months

Death 0.6% 0.4% 0.3%

New-onset end-stage renal disease 0.0% 0.2% 0.3%

Significant embolic event resulting in end-organ damage

0.3% 0.0% 0.0%

Renal artery re-intervention 0.0% 0.2% 0.0%

Vascular complication 0.3% 0.4% 0.7%

Hypertensive crisis/emergency 2.6% 1.0% 1.7%

New renal artery stenosis >70% 0.3% 0.0% 0.0%

Safety in HTN-3 and GSR

*With ≥3 antihypertensive medication classes.


Change in Office SBP at 6 Months for GSR and SYMPLICITY HTN-3 Patients


Change in Office SBP at 6 Months for GSR and Non–African American Patients in SYMPLICITY HTN-3


Change in Ambulatory SBP for GSR and SYMPLICITY HTN-3 Patients


Distribution of SBP in Patients With Office SBP≥160 mm Hg and Ambulatory SBP ≥135 mm Hg* at Baseline


S-22• Excellent procedural and clinical safety profile in the largest data

set of real-world RDN patients to date.

• Significant reductions in both office and ambulatory BP from baseline.– Differences from SYMPLICITY HTN-3 include randomization,

blinding, sham control, BP inclusion criteria, antihypertensive-drug treatment intensity, and an African American cohort in HTN-3.

– Despite the limitations of comparing a registry with a randomized, blinded, controlled study, the reduction in blood pressure is numerically larger in the GSR at 6 months after treatment.

– Due to the nature of registry studies, it is difficult to account for the magnitude of a possible placebo effect in GSR.

LBCT Conclusions


Medtronic Next Steps

• Medtronic will continue to provide access to the Symplicity™ system in

countries where it has regulatory approval and will continue to support a

global hypertension clinical program.

• Medtronic will continue to enroll in the Global SYMPLICITY Registry.

• Our detailed analyses of SYMPLICITY HTN-3 suggest that further

investigation is warranted; Medtronic is in discussions with the FDA to

determine the path forward for the next US IDE trial.

• In light of the results of the SYMPLICITY HTN-3 trial, Medtronic will

discontinue the already suspended SYMPLICITY HTN-4 trial.

• Medtronic will consult with local regulatory bodies to determine the future

of the HTN-Japan and HTN-India clinical studies.

• Medtronic will continue to pursue its studies in other disease states,

including AF, CKD, HF, etc.


www.medtronic.comwww.medtronicRDN.com

Latin AmericaMedtronic USA, Inc.Doral Corporate Center II3750 NW 87th Avenue, Suite 700Miami, FL 33178USATel: 305.500.9328Fax: 786.709.4244

Asia PacificMedtronic Intl. Ltd.49 Changi South Avenue 2Nasco Tech CenterSingapore 486056SingaporeTel: 65.6436.5000Fax: 65.6776.6335

CanadaMedtronic of Canada Ltd.99 Hereford StreetBrampton, Ontario L6Y0R3CanadaTel: 905.460.3800Fax: 905.460.3998Toll-free: 800.268.5346

EuropeMedtronic Intl. Trading SARLRoute du Molliau 31Case PostaleCH-1131 TolochenazSwitzerlandTel: 41.21.802.7000Fax: 41.21.802.7900

United StatesMedtronic USA, Inc.3576 Unocal PlaceSanta Rosa, CA 95403USATel: 707.525.0111

LifeLine Customer SupportTel: 877.526.7890Tel: 763.526.7890

Product ServicesTel: 888.283.7868Fax: 800.838.3103


Appendix


Expanded results presented at the European Society of Cardiology Annual Meeting, 2013.

P < 0.01 for from baseline for all time points.Data is reported only on the patients available at each time point.

Ch

an

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in B

loo

d P

ress

ure

(m

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SYMPLICITY HTN-1: Significant, Sustained BP Reduction to 3 Years

6 Months(N = 144)

1 Year(N = 132)

2 Years(N = 105)

3 Years(N = 88)

Systolic

Diastolic


SYMPLICITY HTN-2: BP Reductions Sustained to 3 Years

Sustained Reductions in the Pooled (RDN and Crossover) Group*

P <0.01 at all time points

∆ F

rom

Ba

selin

e

to

36

Mo

nth

s (m

m H

g)

30 MonthsN = 69

24 Months N = 69

6 MonthsN = 84

12 MonthsN = 80

18 MonthsN = 74

36 MonthsN = 40

*Crossover patients only had 30 months post-procedure data.

Whitbourn, TCT 2013

Systolic

Diastolic


Multiple Unblinded Trials Show RDN Lowers Blood Pressure

N=1

53

N=1

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13

N=1

09

N=3

46

N=6

3N

=15

Published Sources:1. Lancet 20092. Lancet 20103. TCT 20134. Journal of Human Hypertension 20135. Circulation 20136. Clin Res Cardiol 20137. J Am Soc Nephrol 20128. Eur Heart J 20139. TCT 201310. Eurointervention 201311. EuroIntervention 2013

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Medtronic RDN Global Symplicity Registry (GSR)

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