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 www.tomluescher.ch
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
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
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
The Sympathetic Nervous System in the Abdomen
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
Sympathetic Splanchinektomy in Resistant Hypertension: Clinical Results Smithwick R, JAMA, 1953, 16:136-44
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
Managing Treatment-Resistant Hypertension: Systolic-Diastolic versus Systolic Hypertension
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
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)
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 178.2 180.1 178.6 180.3 178.2 180.5 179.0 179.4 179.1 179.7 178.3 181.3 181.9 182.3 183.2 182.8 185.4 189.4 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
DENERHTN Trial – Renal Nerve Ablation withsingle electrode radiofrequency Symplicity catheter (Medtronic)
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?
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
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?
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?
Sympathetic Renal Activity is Increaed in Young, but not Old Hypertensives
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!