Author + information
- George L. Bakris, MD∗ ( and )
- Deepak L. Bhatt, MD, MPH
- ↵∗ASH Comprehensive Hypertension Center, The University of Chicago Medicine, 5841 South Maryland Avenue, MC 1027, Chicago, Illinois 60637
We appreciate Dr. Middlekauff’s interest in the results of SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) and her thoughtful letter suggesting an alternative explanation for the failure to demonstrate a benefit of renal denervation based on ambulatory blood pressure monitoring. The research cited by Esler et al. (1) and Lambert et al. (2) provides interesting evidence that the role of sympathetic nervous system hyperactivity in the etiology of essential hypertension is different between obese and lean patients with hypertension. However, the clinical implications of the difference in sympathetic nerve firing between obese and lean hypertensive patients are unknown.
We undertook a post-hoc analysis of the blood pressure–lowering effect of renal denervation compared with sham control according tertiles of body mass index (BMI). No differences between renal denervation and sham were found. Further exploration of results in patients with a normal BMI (≤27 kg/m2) also revealed no difference between denervation and sham groups (Table 1). We did observe a smaller, albeit nonsignificant, fall in ambulatory blood pressure among lean compared with obese subjects in both treatment groups.
The adipocyte produces aldosterone, so we investigated the effect of spironolactone according to BMI (3). Spironolactone use produced no significant differences in ambulatory blood pressure endpoints between obese and normal weight patients. Moreover, among the denervation subgroup receiving spironolactone at baseline, there was no difference in blood pressure change between the obese (n = 26; BMI >38 kg/m2) and the lean (n = 21; BMI <30 kg/m2) patients (−8.3 ± 12.5 mm Hg vs. −10.4 ± 13.7 mm Hg; p = 0.59). Additionally, spironolactone in obese sham subjects (n = 14) failed to provide a significant drop in blood pressure compared with lean sham subjects receiving spironolactone (n = 8; −9.4 ± 15.7 mm Hg vs. 0.3 ± 19.5 mm Hg; p = 0.22).
Given the overall neutral results of SYMPLICITY HTN-3 (4,5), it is difficult to draw any meaningful conclusions from these data. Additional post-hoc analysis of SYMPLICITY HTN-3 data by our group have proposed several potential factors, including those involving procedural factors, medication adherence, and patient subgroups. These analyses further highlight the importance of well-designed, randomized, sham-controlled clinical trials to clarify our understanding of the potential role for renal denervation in the management of uncontrolled hypertension in obese and lean patients.
Please note: Dr. Bakris has received consultant fees from Takeda, AbbVie, Novartis, Janssen, BMS, Bayer, Medtronic, Relypsa, Orexigen, Merck, and GSK; and has grant funding of an investigator-initiated grant from Takeda; is the editor of the American Journal of Nephrology and Hypertension section of UpToDate; and is associate editor of Diabetes Care and section editor of Nephrology, Dialysis and Transplant. Dr. Bhatt is on Advisory Boards for Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; is on the Board of Directors for Boston VA Research Institute and Society of Cardiovascular Patient Care; is chair of the American Heart Association Get With The Guidelines Steering Committee; is on Data Monitoring Committees for Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute (including for EnligHTNment); and receives honoraria from the American College of Cardiology (editor, Clinical Trials, Cardiosource), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (editor in chief, Journal of Invasive Cardiology), Population Health Research Institute (clinical trial steering committee), Slack Publications (chief medical editor, Cardiology Today’s Intervention), WebMD (CME steering committees), Clinical Cardiology (associate editor), Journal of the American College of Cardiology (section editor, Pharmacology); has received research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic (as co-principal investigator of SYMPLICITY HTN-3), Roche, Sanofi, and The Medicines Company; and has performed unfunded research for FlowCo, PLx Pharma, and Takeda.
- American College of Cardiology Foundation