Effects of Renal Denervation vs Sham in Resistant Hypertension After Medication Escalation: Prespecified Analysis at 6 Months of the RADIANCE-HTN TRIO Randomized Clinical Trial

Abstract

Importance: Although early trials of endovascular renal denervation (RDN) for patients with resistant hypertension (RHTN) reported inconsistent results, ultrasound RDN (uRDN) was found to decrease blood pressure (BP) vs sham at 2 months in patients with RHTN taking stable background medications in the Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN TRIO) trial.

Objectives: To report the prespecified analysis of the persistence of the BP effects and safety of uRDN vs sham at 6 months in conjunction with escalating antihypertensive medications.

Design, setting, and participants: This randomized, sham-controlled, clinical trial with outcome assessors and patients blinded to treatment assignment, enrolled patients from March 11, 2016, to March 13, 2020. This was an international, multicenter study conducted in the US and Europe. Participants with daytime ambulatory BP of 135/85 mm Hg or higher after 4 weeks of single-pill triple-combination treatment (angiotensin-receptor blocker, calcium channel blocker, and thiazide diuretic) with estimated glomerular filtration rate (eGFR) of 40 mL/min/1.73 m2 or greater were randomly assigned to uRDN or sham with medications unchanged through 2 months. From 2 to 5 months, if monthly home BP was 135/85 mm Hg or higher, standardized stepped-care antihypertensive treatment starting with aldosterone antagonists was initiated under blinding to treatment assignment.

Interventions: uRDN vs sham procedure in conjunction with added medications to target BP control.

Main outcomes and measures: Six-month change in medications, change in daytime ambulatory systolic BP, change in home systolic BP adjusted for baseline BP and medications, and safety.

Results: A total of 65 of 69 participants in the uRDN group and 64 of 67 participants in the sham group (mean [SD] age, 52.4 [8.3] years; 104 male [80.6%]) with a mean (SD) eGFR of 81.5 (22.8) mL/min/1.73 m2 had 6-month daytime ambulatory BP measurements. Fewer medications were added in the uRDN group (mean [SD], 0.7 [1.0] medications) vs sham (mean [SD], 1.1 [1.1] medications; P = .045) and fewer patients in the uRDN group received aldosterone antagonists at 6 months (26 of 65 [40.0%] vs 39 of 64 [60.9%]; P = .02). Despite less intensive standardized stepped-care antihypertensive treatment, mean (SD) daytime ambulatory BP at 6 months was 138.3 (15.1) mm Hg with uRDN vs 139.0 (14.3) mm Hg with sham (additional decreases of -2.4 [16.6] vs -7.0 [16.7] mm Hg from month 2, respectively), whereas home SBP was lowered to a greater extent with uRDN by 4.3 mm Hg (95% CI, 0.5-8.1 mm Hg; P = .03) in a mixed model adjusting for baseline and number of medications. Adverse events were infrequent and similar between groups.

Conclusions and relevance: In this study, in patients with RHTN initially randomly assigned to uRDN or a sham procedure and who had persistent elevation of BP at 2 months after the procedure, standardized stepped-care antihypertensive treatment escalation resulted in similar BP reduction in both groups at 6 months, with fewer additional medications required in the uRDN group.

Trial registration: ClinicalTrials.gov Identifier: NCT02649426.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Azizi reported receiving grants from Recor, the French Ministry of Health, Idorsia, Quantum Genomics, and European Horizon 2020; and personal fees from CVRx, AstraZeneca, Medtronic, Alnylam Pharmaceutical, Novartis, and Poxel outside the submitted work. Dr Mahfoud reported receiving personal fees from FM; being supported by Deutsche Gesellschaft für Kardiologie, Deutsche Forschungsgemeinschaft, and Deutsche Herzstiftung; and receiving scientific support from Medronic, ReCor Medical, and Berlin Chemie, and speaker honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, and ReCor Medical during the conduct of the study. Dr Weber reported receiving personal fees from ReCor Medical, Medtronic, Boston Scientific, and Ablative Solutions outside the submitted work. Dr Schmieder reported receiving grant and personal fees from Recor Medical, Medtronic, and Ablative Solutions outside the submitted work. Dr Lurz reported receiving grants from ReCor Medical, Abbott Medical, and Edwards Lifesciences and personal fees from ReCor Medical outside the submitted work. Dr Lobo reported receiving personal fees from ReCor Medical, Medtronic, CVRx, Ablative Solutions, Vascular Dynamics, ROX Medical, Aktiia, and Tarilan Laser Technologies and grants from Medtronic. Dr Fisher reported receiving grants from Recor Medical and consultant fees from Medtronic, Recor Medical, and Aktiia outside the submitted work. Dr Daemen reported receiving institutional grant/research support from AstraZeneca, Abbott Vascular, Boston Scientific, ACIST Medical, Medtronic, Microport, Pie Medical, PulseCath, and ReCor Medical and consultant/speaker fees from Abiomed, ACIST Medical, Boston Scientific, PulseCath, Pie Medical, Siemens Health Care, ReCor Medical, and Medtronic. Dr Bloch reported receiving personal fees from Recor and Medtronic outside the submitted work. Dr Basile reported receiving grants from ReCor Medical and Ablative Solutions; serving on the Medtronic Clinical Events Committee during the conduct of the study; and consultant fees from ReCor Medical outside the submitted work. Dr Sanghvi reported receiving grant support and personal fees from ReCor Medical and Medtronic and grant support from CSI. Dr Saxena reported receiving grants from Recor Medical, Ablative Solutions, Applied Therapeutics, and Vascular Dynamics and speaker/consultant fees from Recor Medical, Esperion Inc, Daiichi-Sankyo Inc, and Vifor Pharma outside the submitted work. Dr Gosse reported receiving grants from Recor Medical and Ablative Solutions during the conduct of the study. Dr Jenkins reported receiving institutional funding to Ochsner Medical Center from Medtronic, Abbott, Abiomed, and ReCor Medical and honorarium for speaking engagements and/or proctoring consulting from Abbott, Recor Medical, and Medtronics. Dr Persu reported receiving grant support, honoraria for consultancy, and travel grants from Recor Medical, Ablative Solutions, Servier, Quantum Genomics and personal fees from Servier outside the submitted work. Ms Claude reported receiving personal fees from ReCor Medical during the conduct of the study and being an employee of ReCor Medical, the sponsor of the study. Dr Reeve-Stoffer reported being an employee of ReCor Medical during the conduct of the study. Dr McClure reported being an employee of NAMSA, a contractor for ReCor Medical. Dr Kirtane reported receiving grants from ReCor Medical and institutional funding to Columbia University and/or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Amgen, CSI, CathWorks, Philips, ReCor Medical, Neurotronic, Biotronik, Chiesi, Bolt Medical, Magenta Medical, Canon, SoniVie, Shockwave Medical, and Merck (institutional funding includes fees paid to Columbia University and/or Cardiovascular Research Foundation for consulting and/or speaking engagements in which Dr Kirtane controlled the content); and receiving consulting fees from IMDS; travel expenses/meals from Medtronic, Boston Scientific, Abiomed, Abbott Vascular, CSI, CathWorks, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron. No other disclosures were reported.

Figures

Figure 1.. Participant Flow Chart

uRDN indicates ultrasound renal denervation.

Figure 2.. Percentage of Patients Taking an Aldosterone-Receptor Antagonist and Corresponding 7-Day Home Systolic Blood Pressure (SBP) Measurements

Data were captured monthly from randomization to 6 months in the ultrasound renal denervation (uRDN) group (n = 65) and the sham group (n = 64) in the analysis population. The mean of 7-day home SBP values is shown. The number of patients with available data in each group is shown in parentheses below the x-axis. A, An aldosterone-receptor antagonist was much less frequently added at each monthly visit in the uRDN group by physicians blinded to the randomization compared with the sham group though 6 months (overall odds ratio, 0.4; 95% CI, 0.2-0.7; absolute risk difference: −15.1%; 95% CI, −23.9% to −6.2%; P < .001). B, The overall decrease in home SBP from baseline to 1, 2, 3, 4, 5, and 6 months was greater in the uRDN group than in the sham group (estimated overall between-group difference: −4.3 mm Hg; 95% CI, −8.1 to −0.5 mm Hg; P = .03 in a mixed linear model adjusting for baseline and medications added).

Figure 3.. Individual Changes in Daytime Ambulatory Systolic Blood Pressure (BP) From Baseline to 6 Months in the Analysis Population

A, Ultrasound renal denervation group (n = 65). B, Sham group (n = 64).