1. CRT 2014
Washington DC, Feb 22-25, 2014
Renal Denervation with a Percutaneous Bipolar Radiofrequency Balloon Catheter in Patients with Resistant Hypertension: 6-Month Efficacy and Safety Results from the REDUCE-HTN Trial
Horst Sievert
On behalf of the REDUCE-HTN Investigators
CardioVascular Center Frankfurt CVC
Frankfurt, Germany

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., 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, Viacor, Inc.

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

5. Renal Denervation for Resistant Hypertension
More than 25% of adults have hypertension1-4
Between 5%-30% of these patients have elevated blood pressure despite aggressive medical treatment5,6
It has been shown that renal denervation reduces blood pressure in patients with resistant hypertension5
Mancia G, Fagard R, Narkiewicz K, et al ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. Jul 2013;31(7):
Persell SD. Prevalence of resistant hypertension in the United States, Hypertension. Jun 2011;57(6):
Kearney et al. Lancet 2005;365:217-23
Lloyd-Jones et al. Circulation 2010;121:e46–e215
Wolf-Meier et al. JAMA 2003;289:2363–2369
Sekikawa and Hayakawa. J Hum Hypertens 2004;18:
Mancia et al. J Hypertens 2013;31(7):
Persell. Hypertension 2011;57(6):

6. Vessix Renal Denervation System
Balloon-based technology
4 - 7 mm diameters
Bipolar radiofrequency electrodes
30 second treatment time
All electrodes are activated simultaneously
Bipolar energy delivery, ~1 Watt
Temperature-controlled algorithm ensures energy delivery at 68°C
One button operation
Approved in Europe (CE mark) and Australia

7. REDUCE-HTN Clinical Sites
Institution
Principal Investigator
Parcelsus Medical University
Prof. Dr. Uta C. Hoppe
Allgemein Affentliches Krankenhaus der Stad Linz
Prof. Dr. Clemens Steinwender
Onze-Lieve-Vrouwziekenhuis, (OLVZ)
Dr. Eric Wyffels
Monash Heart Southern Health
Prof. Dr. Ian Meredith
CardioVasculares Centrum (CVC) Frankfurt
Prof. Dr. med Horst Sievert
George Pompidou Hospital
Prof. Dr. Michel Azizi
The Prince Charles Hospital
Associate Prof. Darren Walters
Cardiology Center Geneva university Hospitals
Dr. Georg Ehret
Auckland City Hospital
Dr. Mark Webster
Flinders Medical Centre
Dr. Ajay Sinhal
Erasmus Medical Center
Dr. Joost Daemen
Vascular Center Berlin
Dr. Ralf Langhoff
Main Tanus Kliniken
Prof. Dr. med. Nicolaus Reifart
St. Vincent's
Dr. David Muller
Zentrum für Gefäßmedizin
Prof. Dierk Scheinert
Academic Medical Center
Prof. Robbert-Jan de Winter
Cliniques Universitaires Saint Luc
Prof. dr. Alexandre Persu
Clinique Pasteur
Prof. Jean Fajadet
German Heart Centre
Prof. Dr. med. Ilka Ott
Universitäres Herz- und Gefäßzentrum Hamburg
Prof. Dr. med. Joachim Schofer
Zentralklinik Bad Berka GmbH
Dr. med. Ahmed Farah
Royal Adelaide Hospital
Prof. Steven Worthley
Mercy Angiography - Auckland
Dr. John Ormiston

8. REDUCE-HTN FIM + PMS Key Inclusion Criteria
PMS (N=128)
FIM (N=18)
REDUCE-HTN
FIM + PMS (N=146)
Office-based blood pressure (average of 3 readings):
First in Man (FIM): SBP ≥ 160 mmHg
Post-Market Study (PMS): SBP/DBP ≥ 160/90 mmHg
≥ 3 antihypertensive drugs at maximally tolerated doses with stable regimen for at least 2 weeks prior to enrollment
Renal artery length:
FIM: ≥ 20 mm
PMS: ≥ 15 mm
Renal artery without significant stenosis (i.e., baseline diameter stenosis <30%)
Main renal artery diameter of ≥ 3.5 mm and ≤ 7.0 mm for each kidney:
FIM: Single renal artery
PMS: Subjects with accessory renal arteries were enrolled

9. REDUCE-HTN FIM + PMS Study Endpoints
Efficacy
Reduction of office-based blood pressures at 6 months
Reduction of 24-hour ambulatory blood pressure at 6 months
Safety Endpoints
Acute Safety
Renal artery dissection or perforation during the procedure that requires stenting or surgery
Renal artery infarction or embolus
Periprocedural cerebrovascular accident
Periprocedural myocardial infarction
Periprocedural sudden cardiac death
Long-term Safety
Renal stenosis requiring an intervention, documented by angiography
Duplex ultrasound required at 6 months to assess absence of flow limiting stenosis in the renal artery (core lab analysis)
Renal function (eGFR)
Primary endpoint analysis includes 142 patients who have completed 6 months of follow-up (97% of enrolled patients)

10. Baseline Demographic and Clinical Characteristics
Demographic Characteristics
Age (years)
58.6±10.5
Gender (male)
61.0%
Ethnic origin (white)
92.5%
Comorbidities
Type 2 diabetes
28.1%
Coronary artery disease
37.7%
Dyslipidemia
58.2%
Congestive heart failure
2.1%
Blood Pressure
Systolic blood pressure (mmHg)
182.4±18.4
Diastolic blood pressure (mmHg)
100.2±14.0
Kidney Function
eGFR (mL/min/1.73 m2)
83.9±24.1
Serum creatinine (μmol/L)
82.1±19.8
eGFR=estimated glomerular filtration rate

11. Baseline Antihypertensive Medications
Number of antihypertensive medications per patient
5.3±1.9
≥5 Medications
61.6%
4 Medications
21.9%
3 Medications
13.0%
Percentage of Patients Receiving:
ACE Inhibitors or ARBs
93.2%
β Blockers
78.1%
Diuretics
76.7%
Calcium Channel Blockers
75.3%
Centrally Acting Sympatholytic
39.7%
α-1 Blockers
34.2%
Aldosterone Antagonist
29.5%
Nitrate and Other Vasodilators
15.1%
Direct Renin Inhibitors
11.0%
Other Antihypertensive
2.7%
ACE=angiotensin-converting enzyme; ARB=angiotensin-receptor blocker

12. Significant Office Blood Pressure Reductions Over Time
Mean reduction in office-based BP was 24.7/10.3 mmHg at 6 months (P<.0001)
P<.0001 for each timepoint vs baseline.
Error bars represent 95% confidence bounds.
BP=blood pressure

13. Blood Pressure Response
85% of patients had a clinically meaningful response to treatment1 based on office systolic BP at 6 months
Whelton PK, He J, Appel LJ, et al. Primary prevention of hypertension: clinical and public health advisory from the National High Blood Pressure Education Program. JAMA. 2002; 288: 1882–1888.
BP=blood pressure
Whelton et al. JAMA 2002;288: (National High Blood Pressure Education Program).

14. Target Office Pressure Achievement
Office-based systolic BP <140 mmHg was reached by 18% of patients at 6 months
BP=blood pressure

15. Significant Reductions in 24-hour Ambulatory Blood Pressures
Baseline mean 24-hour ambulatory blood pressure was 153/88 mmHg (n=103)
Mean reduction at 6 months was 8.4/5.9 mmHg (P<.0001; n=69)
P<.0001 vs baseline.
Error bars represent 95% confidence bounds.
ABP=ambulatory blood pressure

16. Target Ambulatory Blood Pressure Achievement
Ambulatory systolic BP <140 mmHg was reached by 34% of patients at 6 months
BP=blood pressure

17. 24-hour Ambulatory Blood Pressure Reductions
85% of patients who had ambulatory BP measurements (88/103) had ambulatory systolic BP >140 mmHg at baseline
The reduction in ambulatory systolic BP at 6 months was greatest for patients with higher baseline pressure
Change in Ambulatory Systolic BP at 6 Months
Error bars represent 95% confidence bounds.
BP=blood pressure

18. Significant Office Blood Pressure Reductions for Patients with Accessory Renal Arteries (n=24)
P<.0005 for each timepoint vs baseline.
Error bars represent 95% confidence bounds.
BP=blood pressure

19. Significant Office Blood Pressure Reductions for Men (n=89) and Women (n=57)
P<.0001 for each timepoint vs baseline (within subgroup).
Error bars represent 95% confidence bounds.

20. Diabetes Subgroup (n=34)
Significant Office Blood Pressure Reduction for Diabetes and Age ≥65 Subgroups
Diabetes Subgroup (n=34)
Age ≥65 Years (n=43)
P<.0001 for each timepoint vs baseline
P<.0001 for each timepoint vs baseline
Change in Office Systolic BP
Change in Office Diastolic BP
Error bars represent 95% confidence bounds.
BP=blood pressure

21. Renal Function Mean eGFR changed -0.9±16.4 mL/min/1.73 m2 at 6 months
At 6 months, 10.9% (15/138) of patients had a reduction in eGFR >25% from baseline
Only 2 of these patients had kidney-related adverse events, and neither of them were determined to be related to the procedure by the Data Safety Monitoring Board:
Renal insufficiency at 3 months
Acute renal failure at 6 months
eGFR=estimated glomerular filtration rate

22. No Acute Safety Events and Low Rate of Procedure-Related SAEs
No patient experienced prespecified acute safety events
Low rate of procedure-related serious adverse eventsa (5.5%) among the 146 patients
Hematoma (1)
Bilateral flank pain (1)
Vomiting (1)
Access site infection (2)
Pseudoaneurysm at access site (1)
Femoral artery thrombus (1)
Renal artery stenosis requiring treatment (1)
Baseline stenosis was 17% based on core lab assessment of angiogram; stenosis of 60% noted by angiography at 6 month follow-up; patient received percutaneous transluminal angioplasty/stent and continues to be monitored.
6-month patencyb 99.2% by DUS (248/250 arteries)
aSerious adverse events (SAEs) defined according to International Organization for Standardization ISO14155.
bPatency defined as stenosis <60%.
DUS=duplex ultrasound

23. Conclusions
The Vessix System is a safe and effective method for the treatment of resistant hypertension
Significant office blood pressure reductions through 6 months
Significant reductions for patients with accessory renal arteries
Significant reductions for patients ≥65 years of age, those with diabetes, and both sexes
85% of patients had an office systolic BP reduction of at least 5 mmHg at 6 months
Ambulatory systolic BP was below 140 mmHg at 6 months in 34% of the patients

24. Thank you!