1. Critical Appraisal of the Current Ongoing Study Designs
CRT 2017, Washington, DC, USA
Renal Denervation: New Data and
Clinical Trial Desing Update
Critical Appraisal of the Current
Ongoing Study Designs
Thomas F. Lüscher, FESC, FAHA, FRCP
Professor and Chairman of Cardiology and Director, Center for Molecular Cardiology, University and University Hospital Zurich

2. Renal Denervation: New Data and Clinical Trial Desing Update
CRT 2017, Washington, DC, USA
Renal Denervation: New Data and
Clinical Trial Desing Update
Disclosure:
Boston Scientific Research Grant
Medtronic Research Grant
St. Jude Educational Grant

3. Critical Appraisal of the Current Ongoing Study Designs
CRT 2017, Washington, DC, USA
Renal Denervation: New Data and
Clinical Trial Desing Update
Critical Appraisal of the Current
Ongoing Study Designs
Surgical Sympathectomy
Registries
Published Trial
Problems of Published Trial
Ongoing Trials
Conclusion

4. Critical Appraisal of the Current Ongoing Study Designs
CRT 2017, Washington, DC, USA
Renal Denervation: New Data and
Clinical Trial Desing Update
Critical Appraisal of the Current
Ongoing Study Designs
Surgical Sympathectomy
Registries
Published Trial
Problems of Published Trial
Ongoing Trials
Conclusion

5. The Sympathetic Nervous System in the Abdomen

6. Critical Appraisal of the Current Ongoing Study Designs
Sympathectomy in Severe Hypertension:
The Pioneer
CRT 2017, Washington, DC, USA
Renal Denervation: New Data and
Clinical Trial Desing Update
Critical Appraisal of the Current
Ongoing Study Designs
Surgical Sympathectomy
Registries
Published Trial
Problems of Published Trial
Ongoing Trials
Conclusion

7. Sympathetic Splanchinektomy in Resistant
Hypertension: Clinical Results
Smithwick R, JAMA, 1953, 16:136-44

8. Critical Appraisal of the Current Ongoing Study Designs Registries
CRT 2017, Washington, DC, USA
Renal Denervation: New Data and
Clinical Trial Desing Update
Critical Appraisal of the Current
Ongoing Study Designs
Surgical Sympathectomy
Registries
Published Trial
Problems of Published Trial
Ongoing Trials
Conclusion

10. Managing Treatment-Resistant Hypertension:
Systolic-Diastolic versus Systolic Hypertension

11. Critical Appraisal of the Current Ongoing Study Designs
CRT 2017, Washington, DC, USA
Renal Denervation: New Data and
Clinical Trial Desing Update
Critical Appraisal of the Current
Ongoing Study Designs
Surgical Sympathectomy
Registries
Published Trial
Problems of Published Trial
Ongoing Trials
Conclusion

14. PROs and CONs of Symplicity HTN-3
Randomized
Good size (appropriate power)
Double blind
Sham procedure
Appropriate statistics
Questionalbe stabilization of BP before RNA
More than 5 antihyperten-sive drugs
Few recruited patients by center
Unexperienced operators
Single electorde device
Few ablations in many patients (<6)

15. Impact of Number of Ablations on Change in Office SBP: Symplicity-HTN3 Matched Cohort Analysis
166
155
134
100 63 46 27 19 10
N=163
152
131 98 61 45 26 18 9
P value for trend= 0.01
Baseline SBP
95% CI P*
-1.7(-7.1, 3.7)
0.54
-3.1 (-8.6, 2.4)
0.27
-5.4 (-11.3, 0.5)
0.07
-7.1 (-13.9,-0.3)
0.04
-8.4 (-17.4, 0.7)
-11.5 (-21.8,-1.2)
0.03
-14.1 (-28.8, 0.7)
0.06
-12.0 (-30.0, 5.9)
0.18
-12.4 (-44.6, 19.8)
0.43
Propensity scores using baseline characteristics as covariates were used to match sham control and denervation patients
*P value change in SBP for RDN compared with sham
Data presented are mean (SD)
David E. Kandzari et al. Eur. Heart J. 2015

16. DENERHTN Trial – Renal Nerve Ablation withsingle electrode
radiofrequency Symplicity catheter (Medtronic)

17. Renal Denervation: New Data and Clinical Trial Desing Update
CRT 2017, Washington, DC, USA
Renal Denervation: New Data and
Clinical Trial Desing Update
What did we learn from Symplicity HTN-3?
Double-blind sham design
Proper stabilization of BP important
Appropriate ablation technique
Better devices
Distal Ablation
Consistant drug regimen
Resistant Hypertension?

18. Renal Denervation: New Data and Clinical Trial Desing Update
CRT 2017, Washington, DC, USA
Renal Denervation: New Data and
Clinical Trial Desing Update
New Devices
Mulitelectrode devices
with option to provide
A persistant nerve block
are mandatory

19. Which patient? Old or Young? Afroamericans of caucasians?
CRT 2017, Washington, DC, USA
Renal Denervation: New Data and
Clinical Trial Desing Update
Which patient?
Old or Young?
Afroamericans of caucasians?
Systolic or systolic-diastolic hypertension?
Resistant or moderate?
Treated or untreated?

20. Which patient? Old or Young? Afroamericans of caucasians?
CRT 2017, Washington, DC, USA
Renal Denervation: New Data and
Clinical Trial Desing Update
Which patient?
Old or Young?
Afroamericans of caucasians?
Systolic or systolic-diastolic hypertension?
Resistant or moderate?
Treated or untreated?

21. Sympathetic Renal Activity is Increaed in Young,
but not Old Hypertensives

27. Critical Appraisal of the Current Ungoing Studies Design
CRT 2017, Washington, DC, USA
Critical Appraisal of the Current
Ungoing Studies Design
Surgical renal sympathectomy works
We have to prove that catheter-based ablation works, with which device and in which patients
Double-blind sham design is mandatory
Untreated younger hyperternsives would be the best population to prove this
Thank You!