Patient-Level Pooled Analysis of Endovascular Ultrasound Renal Denervation or a Sham Procedure 6 Months After Medication Escalation: The RADIANCE Clinical Trial Program.

Background: The randomized, sham-controlled RADIANCE-HTN (A Study of the Recor Medical Paradise System in Clinical Hypertension) SOLO, RADIANCE-HTN TRIO, and RADIANCE II (A Study of the Recor Medical Paradise System in Stage II Hypertension) trials independently met their primary end point of a greater reduction in daytime ambulatory systolic blood pressure (SBP) 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN versus sham at 6 months, after the blinded addition of antihypertensive treatments (AHTs), we pooled individual patient data across these 3 similarly designed trials.
Methods: Patients with mild to moderate hypertension who were not on AHT or with hypertension resistant to a standardized combination triple AHT were randomized to uRDN (n=293) versus sham (n=213); they were to remain off of added AHT throughout 2 months of follow-up unless specified blood pressure (BP) criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mm Hg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mm Hg under blinding to initial treatment assignment. Six-month outcomes included baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP; change in AHT; and safety. Linear mixed regression models using all BP measurements and change in AHT from baseline through 6 months were used.
Results: Patients (70% men) were 54.1±9.3 years of age with a baseline daytime ambulatory/home/office SBP of 150.5±9.8/151.0±12.4/155.5±14.4 mm Hg, respectively. From 2 to 6 months, BP decreased in both groups with AHT titration, but fewer uRDN patients were prescribed AHT ( P =0.004), and fewer additional AHT were prescribed to uRDN patients versus sham patients ( P =0.001). Whereas the unadjusted between-group difference in daytime ambulatory SBP was similar at 6 months, the baseline and medication-adjusted between-group difference at 6 months was -3.0 mm Hg (95% CI, -5.7, -0.2; P =0.033), in favor of uRDN+AHT. For home and office SBP, the adjusted between-group differences in favor of uRDN+AHT over 6 months were -5.4 mm Hg (-6.8, -4.0; P <0.001) and -5.2 mm Hg (-7.1, -3.3; P <0.001), respectively. There was no heterogeneity between trials. Safety outcomes were few and did not differ between groups.
Conclusions: This individual patient-data analysis of 506 patients included in the RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN versus sham at 6 months, with fewer added AHTs.
Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02649426 and NCT03614260.
Competing Interests: Disclosures Dr Azizi reports receiving grants from the European Horizon 2020 program; grants and nonfinancial support from Recor Medical, Idorsia, and Novartis; and personal fees from Alnylam Pharmaceuticals, Cincor, Medtronic, AstraZeneca, and Novartis. Dr Sharp has received personal fees from Recor Medical, Medtronic, Boston Scientific, Penumbra, and Philips. Dr Fisher has received grant support and personal fees from Recor Medical and personal fees from Medtronic. Dr Lobo has received personal fees from Recor Medical, Medtronic, Ablative Solutions, and Vascular Dynamics; and has received grants from Medtronic. Dr Daemen received institutional grant or research support from Abbott Vascular, Boston Scientific, ACIST Medical, Medtronic, Microport, Pie Medical, and Recor Medical, and consultancy or speaker fees from Abbott Vascular, Abiomed, ACIST Medical, Boston Scientific, Cardialysis BV, CardiacBooster, Kaminari Medical, Recor Medical, PulseCath, Pie Medical, Sanofi, Siemens Health Care, and Medtronic. Dr Lurz has received institutional grant support from Recor Medical, Edwards Lifesciences, and Abbott. Dr Mahfoud is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219, project ID 322900939), and Deutsche Herzstiftung; and has received scientific support from Ablative Solutions, Medtronic, and Recor Medical, and speaker honoraria or consulting fees from Ablative Solutions, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, Recor Medical, Servier, and Terumo. Dr Schmieder has received grant support and personal fees from Recor Medical, Medtronic, and Ablative Solutions. Dr Basile has received grant support from Recor Medical and Ablative Solutions. Dr Bloch has received personal fees from Recor Medical and Medtronic. Dr Weber has received personal fees from Recor Medical, Medtronic, and Ablative Solutions. Dr Saxena has received grant support from Recor Medical, Ablative Solutions, Applied Therapeutics, Vascular Dynamics, and MSD; and has received consulting fees from Recor Medical, Esperion Inc., Daiichi Sankyo Inc., Novartis, and Vifor Pharma. Dr Wang reports no relationships relevant to the contents of this article to disclose. Dr Sanghvi has received grant support and personal fees from Recor Medical and Medtronic and has received grant support from CSI. Dr Jenkins reports institutional funding to Ochsner Medical Center from Medtronic, Abbott, Abiomed, and Recor Medical; and in addition to research grants, he has received honoraria for speaking engagements or proctoring consulting from Abbott, Recor Medical, and Medtronic. Dr Devireddy has received personal fees from Recor Medical, Medtronic, Edwards Lifesciences, and Shockwave Medical. Dr Rader has received personal fees from Recor Medical, Medtronic, and Bristol Myers Squibb. Dr Gosse has received research grant support from Recor Medical. L. Claude and Dr Dimitri Augustin are employees of Recor Medical. Dr McClure is an employee of NAMSA, a contractor for Recor Medical. Dr Kirtane reports institutional funding to Columbia University or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, and Recor Medical; in addition to research grants, institutional funding includes fees paid to Columbia University or Cardiovascular Research Foundation for speaking engagements or consulting; personal fees for consulting from Neurotronic; and travel expenses or meals from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, Recor Medical, Chiesi, OpSens, Zoll, and Regeneron.