1. The Ardian Catheter Based Approach to Renal Denervation to Treat Refractory HTN: Results of the EU Randomized Clinical Trial
Krishna Rocha-Singh, M.D., FACC, FSVM, FSCAI Director, Prairie Vascular Institute Springfield, IL

2. Krishna Rocha-Singh, M.D.
Research
None
Consultant/Advisory Board/Training
Medtronic
ev3, Inc.
Minnow
Ardian (expired)
Royalties/Financial Interest
None
VIVA Board Member salary
Medical Director PERC, salary
I will discuss a vascular device which is unavailable in the US

3. Renal Efferent Nerve Activity
Kidney as the Recipient of Sympathetic Signals
Renal Efferent Nerves
↑ Renin release  ↑ RAAS activation
↑ Sodium retention
↓ Renal Blood Flow 3 3

4. What if We Could Disconnect this Circuit?
Renal Afferent Nerve Activity
The Origin of Central Sympathetic Drive
What if We Could Disconnect this Circuit?
Hypertrophy
Arrhythmia
O2 Consumption
Heart Failure
Vasoconstriction
Atherosclerosis
Renal Afferent Nerves
Insulin Resistance
↑ Renin release  ↑ RAAS activation
↑ Sodium retention
↓ Renal Blood Flow 4

5. Symplicity HTN-1 Study Aims:
First-in-man 12-month evaluation of the safety and blood pressure-lowering efficacy of percutaneous renal sympathetic denervation in patients with refractory hypertension
Study Sites:
Melbourne & Newcastle, Australia; Krakow, Poland; & Frankfurt, Germany
Krum et al. Lancet. 2009;373(9671): 5 5

6. Symplicity HTN-2
Purpose: To demonstrate the effectiveness of catheter-based renal denervation for reducing blood pressure in patients with uncontrolled hypertension in a prospective, randomized, controlled, clinical trial
Patients: 106 patients randomized 1:1 to treatment with renal denervation vs. control
Clinical Sites: 24 centers in Europe, Australia, & New Zealand (67% were designated hypertension centers of excellence)
Symplicity HTN-2 Investigators. The Lancet 2010: 376: 6

7. Randomized Cross-Over Design
Baseline Drop-Outs
Registry
Treatment Group
Control Patients offered treatment
Suboptimal Anatomy
Control Group
Primary Endpoint 6M
12-36M
Anatomical Screening
(MRA, CTA, duplex or angiogram)
24-hr ABPM
Randomized 1:1
Uncontrolled HTN
SBP ≥ 160 mmHg
(≥ 150 mmHg diabetics)
≥ 3 meds
“Baseline”
2 week observation
Baseline BP measure at end of baseline period
ClinicalTrials.gov Identifier: NCT 7

8. Patient Disposition Assessed for Eligibility (n=190)
Excluded Prior to Randomization (n=84)
BP <160 after 2-weeks of compliance confirmation (n=36; 19%)
Ineligible anatomy (n=30; 16%)
Declined participation (n=10; 5%)
Other exclusion criteria discovered after consent (n=8; 4%)
Randomized (n=106)
Allocated to RDN
(n=52)
Allocated to Control
(n = 54)
No Six-Month Primary Endpoint Visit (n = 3)
Reasons:
Withdrew consent (n=1)
Missed visit (n=2)
Withdrew consent (n=2)
Lost to follow-up (n=1)
Analyzed (n = 49)
Analyzed (n = 51)
Symplicity HTN-2 Investigators. The Lancet 2010: 376: . 8

9. Primary Endpoint: 6-Month Office BP
∆ from Baseline to
6 Months (mmHg)
Systolic
Diastolic
Diastolic
33/11 mmHg
difference between RDN and Control
(p<0.0001)
Systolic
84% of RDN patients had ≥ 10 mmHg reduction in SBP
10% of RDN patients had no reduction in SBP
Symplicity HTN-2 Investigators. The Lancet 2010: 376:

10. Procedural Safety
RDN can be safely and easily performed through a 6F guide system - 1 CFA PA - No perforations - No change in GFR

11. RDN…24 Mo Follow-up
Renal denervation is a safe and VERY effective percutaneous therapy resulting in a substantial improvement in BP in patients with resistant HTN through 2 yr follow-up in a small cohort
TCT 2010

12. Unresolved Questions and Challenges:
Can we predict ‘responders’ and ‘non-responders’?
What is the treatment effect’s ‘durability’? ….is it really “a cure”?
Can anatomic limitations be overcome?
What are the anticipatable other beneficial effects/indications which should be considered?

13. A Careful and Regimented Clinical Evaluation
First-in-Man 
Series of Pilot studies 
Symplicity HTN-2
Initial Randomized Clinical Trial 
Symplicity HTN-3
US PMA Randomized Clinical Trial
Lancet Publication 2009
Symplicity HTN n=45
Lancet Publication 2010
n=52
Enrollment to start mid-2011 13