1. Critical Appraisal of Devices for the Management of Hypertension
Professor Atul PATHAK, MD, PhD.
Head of Clinical Research
Director Hypertension and Heart Failure unit
Director of Hi-LAB
Clinique Pasteur , Toulouse
FRANCE

2. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
Grant/Research Support
Consulting Fees/Honoraria
Medtronic, CVRx, Recor, Ablative Solution, SJM

3. What is the most suitable patient population?
Move from RH patient to uncontrolled patient. The RH population might not respond with the greatest fall in BP. Difficulty to find sufficient treatment-resistant severely HTN patients An alternative may be a trial in younger patients with mild hypertension. have greater sympathetic nervous system activation than older patients the arterial wall is more responsive to changes in sympathetic tone plea for extensive phenotyping not “just “ BP recording less treated patient Include option of patient’s preference in the study design. ( combo trial, patient with ADR, compliance issues) What if Isolated systolic HTN or renal disease (eGFR <30 ml/min/1.73 m2)? take into account device specificity (ROX rather than RDN)
Ott C et al. J Am Heart Assoc. 2016 Dec 21;5(12). pii: e doi: /JAHA

4. Variability of response
RDN
Control ?
Azizi M Optimum and Stepped Care Standardised Antihypertensive Treatment with or without Renal Denervation for Resistant Hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial, Lancet 2015; 14: 1-9.

5. What is the most suitable device?
Preclinical evaluation
Animal model, with hypertension
Follow up ( long term)
Per procedural testing
Easy to use
Standardisation of the treatment
Reduced operator variability
Efficacy
Safe :
Follow up
Type of Safety
Standardization : VARC type

6. Technical success verifiable
Critical Appraisal
Devices
Preclinical Data
(published)
Strength of evidence
Sham
possible
Technical success verifiable
Reversible
Specificity
Potential AE
Rox Coupler No
RCT
Yes
ISH possibe
Immediate BP reduction
Venous stenosis
RDN
No ISH
Anatomy
Known
GSR
External Ultrasound
Observational prospective trial
Easy
Ambuatory? ?
Chemical RDN
Case Report
Yes and No
Like RDN
BAT
CHF also
Titration possible
Procedure
Pacemaker like
Adapted from Curr Hypertens Rep (2016) 18: 61

7. How to measure outcome ? Efficacy ?BP
Dose response ?
BP related surrogate
Morbidity
Mortality
Follow up for BP lowering effect
BP lowering effect is a must.
Clinical meaningful

8. ABPM, HBP, office BP, unattended BP ?
ABPM more informative (large number of readings, variability, nocturnal BP)
Strong prognostic value
Detect different phenotypes and exclude pseudo resistance (white coat, stiff arteries, cuff problem in obese patient) interesting for selection
Less bias and placebo effect (blind analysis)
5 mm Hg decrease in daytime SBP clinically meaningful (like in DENER HTN) ?
Lack of recommandation (Standardize all device trial ? )

9. Critical Appraisal of Device Trials
Feasible : external validity
Need for control :What is the sham effect ? Sham procedure is an active treatment per se is it really the appropriate control ?
Optimal procedure and material
Optimize adherence: Stepped care approach, e-tools
Follow up : BP, Surrogate, Imaging, Safety
Alliance: Public funding, common data, health economics
Use the Web to make the clinical trial faster,cheaper, and more efficient.
Patient involvement
Ott C et al. J Hypertens. 2016 Dec;34(12):
Azizi M et al. Circulation. 2016 Sep 20;134(12): doi: /CIRCULATIONAHA

10. Critical Appraisal of other devices
Strength of evidence
Sham
Technical success verifiable
Reversible
Patient
Specificity
Potential AE
Carotid Body Ablation
Observational Feasibility study No
Yes surgical resection
High CB
tone
Verifiable surgical resection ?
Deep Brain Stimulation
Observational
Non BP trial
Yes
? Open loop , no titration
Median Nerve Stimulation
Sham Controlled RCT
Inexpensive
Less invasive
Vagal Nerve Stimulation *
Animal data and case report
Not
yet
Heart Rate
Other system.
Titration
*A study of selective VNS in patients undergoing carotid endarterectomy and coronary artery bypass grafting, with four patients enrolled, has been completed, but the results have not yet been published (clinicaltrials.gov: NCT ).
Adapted from Curr Hypertens Rep (2016) 18: 61

11. Conclusion
Expand Patient Phenotype (autonomic, psychological, physiology, brain –mind connexion)
Standardize Device Evaluation (efficacy, safety)
Improve Strength of Evidence (preclinical and clinical)