1. Catheter-based Renal Denervation with the Symplicity System Provides Safe and Durable Blood Pressure Reduction out to Three Years
Horst Sievert1, Henry Krum2 on behalf of the Symplicity HTN-1 Investigators
1CardioVascular Center Frankfurt, Frankfurt, GERMANY, 2Monash University/Alfred Hospital, Melbourne, Australia

2. Horst Sievert, MD Consulting:
AccessClosure, Inc., AGA Medical Corporation, Ardian, Inc., Arstasis, Inc., Atritech Atrium Medical Corporation, Avinger, Inc., Bard Peripheral Vascular, Inc., Boston Scientific Corporation, Bridgepoint, CardioKinetix Inc., CardioMEMS, Inc., Coherex, Inc., Contego, CSI, EndoCross, Endotex Interventional Systems, Epitek, Evalve, Inc. and ev3, Inc.

3. Horst Sievert, MD Consulting:
FlowCardia, Inc., Gore, Guidant, Lumen Biomedical,
Inc., HLT, Kensey Nash Corporation, Kyoto Medical, Lifetech,
Lutonix, Inc., Medinol, Medtronic, Inc., NDCNMT Medical, Inc.,
OAS, Occlutech Osprey Medical, Inc., Ovalis, Inc., Pathway
Medical Technologies, Inc., PendraCare International B.V., Pfm
Medical, Inc., Rox Medical, Recor, Sadra Medical, Sorin
Biomedica Cardio S.R.L.,and Spectranetics Corporation, Trireme, Trivascular and Viacor, Inc.

4. Horst Sievert, MD
Honoraria: Veryan, Ardian, Inc., Atritech, Atrium Medical Corporation, Boston Scientific Corporation, CardioKinetix Inc.,
CardioMEMS, Inc., Coherex, Inc., Contego, Epitek, Evalve, Inc.,
Guidant,Gore,Kyoto Medical, Lutonix, Inc., Medinol, Medtronic, Inc., Pfm Medical, Inc., and Spectranetics Corporation.

5. Horst Sievert, MD
Honoraria: Viacor, Inc., HLT, Lifetech, Recor, Trivascular, Veryan, CVRx, GDS and InSeal Medical.

6. Symplicity HTN-1 Initial Cohort – Reported in the Lancet, 2009:
Catheter-based Renal Sympathetic Denervation for
Resistant Hypertension
Durability of Blood Pressure Reduction Out to 24 Months
Symplicity HTN-1 Investigators*
Lancet. 2009;373:
Hypertension. 2011;57:
Initial Cohort – Reported in the Lancet, 2009:
First-in-man, non-randomized study conducted in Europe and Australia
Cohort of 45 patients with resistant HTN (SBP ≥160 mmHg on ≥3 anti-HTN drugs, including a diuretic; eGFR ≥ 45 mL/min)
All patients received bilateral renal denervation with the Symplicity™ renal denervation system
Primary endpoint: change in office BP; 1, 3, 6, 9 and 12 months post-procedure
Expanded Cohort – Symplicity HTN-1:
Expanded cohort of patients (n=153) from 19 sites (US, Europe, and Australia)
24 and 36-month follow-up of safety and effectiveness 6

7. Baseline Patient Characteristics (n=153)
Demographics
Age (years)
57 ± 11
Gender (% female)
39%
Race (% non-Caucasian) 5%
Co-morbidities
Diabetes Mellitus II (%)
31%
CAD (%)
22%
Hyperlipidemia (%)
68%
eGFR (mL/min/1.73m2)
83 ± 20
Blood Pressure
Baseline BP (mmHg) (n=150)
175/98 ± 17/15
Number of anti-HTN meds (mean)
5.1 ± 1.4
Diuretic (%)
95%
Aldosterone blocker(%)
ACE/ARB (%)
91%
Direct Renin Inhibitor
14%
Beta-blocker (%)
82%
Calcium channel blocker (%)
75%
Centrally acting sympatholytic (%)
33%
Vasodilator (%)
19%
Alpha-1 blocker
Symplicity HTN-1 Investigators. Hypertension. 2011;57: 7

8. Change in Office Blood Pressure Through 36 Months*
P<0.01 for ∆ from BL
for all time points
Reported as mean with 95% confidence intervals
*Data is reported only on the patients available at each timepoint.
It does not reflect the full cohort

9. Distribution of SBP Change at BL, 1, 12, 24, and 36 Months
% Patients
placeholder
(N=150)
(N=143)
(N=132)
(N=105)
(N=34)

10. Percentage Responders Over Time
Responder was defined as an office SBP reduction ≥10 mmHg
(n=143)
(n=148)
(n=144)
(n=132)
(n=108)
(n=105)
(n=44)
(n=34)

11. Change in Office BP by Age
12 Months
24 Months
36 Months
(mmHg)
Actual values to be added
P<0.01
compared with BL,
†p=0.19
N=98
N=34
N=78
N=27
N=29
N=5

12. Change in Office BP in Diabetic and Non-Diabetic Patients
12 Months
24 Months
36 Months
(mmHg)
Actual values to be added
P<.01
Compared with BL,
†p=0.03 DM
(N=45)
Non-DM
(N=87) DM
(N=31)
Non-DM
(N=74) DM
(N=11)
Non-DM
(N=23)

13. Change in Office BP According to Baseline Renal function
12 Months
24 Months
36 Months
(mmHg) ‡
Actual values to be added
eGFR
45-60
(N=10)
eGFR>60
(N=116) †
eGFR
45-60
(N=9)
eGFR>60
(N=92)
eGFR
45-60
(N=2)
eGFR>60
(N=30)

14. Vascular Complications Out to 36 months
Stenosis (previously reported to 18 months)
One progression of a pre-existing stenosis unrelated to RF treatment (stented without further sequelae)
One new moderate stenosis which was not hemodynamically relevant , requiring no treatment
No new reports of vascular complications*
*Analysis includes data on all patients available through 36 months
Ask Bryan – can this be included
Schlaich M, TCT 2012
Symplicity HTN-1 Investigators. Hypertension. 2011;57: 14

15. Other Adverse Events Out to 36 months*
Hypotension and Renal Failure (18 m) n=1
Due to sepsis, resolved
Hypotension and Renal Failure (24 m) n = 1
Post-operative acute renal failure
resolved
Hypotension Episode (n = 1)
No treatment, resolved
3 deaths, unrelated to procedure
Myocardial Infarction - After 3-day visit
Sudden death (cardiac) - After 6 months
Cardio-respiratory arrest - After 18 months
Ask Bryan – can this be included
*Analysis includes data on all patients available through 36 months
Symplicity HTN-1 Investigators. Hypertension. 2011;57:
Schlaich M – TCT 2012 15

16. Conclusions
The magnitude of clinical response is significant and sustained through 36 months
Increasing responder rates indicate:
Some subjects respond late to RDN
No loss of treatment effect out to 36 months
The treatment effect was consistent across subgroups (age, diabetes status, and baseline renal function)
No late adverse events related to RDN through 36 months
Analysis iincludes data on patients available through 36 months