Patient-Level Pooled Analysis of Endovascular Ultrasound Renal Denervation or a Sham Procedure 6 Months After Medication Escalation: The RADIANCE Clinical Trial Program
Michel Azizi, Andrew Sharp, Naomi D.L. Fisher, Michael A. Weber, Melvin D. Lobo, Joost Daemen, Philipp Lurz, Felix Mahfoud, Roland E. Schmieder, Jan Basile, Michael J. Bloch, Manish Saxena, Yale Wang, Kintur Sanghvi, J. Stephen Jenkins, Chandan Devireddy, Florian Rader, Philippe Gosse, Lisa Claude, Dimitri A. Augustin, Candace K. McClure, Ajay J. Kirtane, Yale Wang, Nedaa Skeik, Richard Bae, Amy McMeans, JoAnne Goldman, Rose Peterson, J. Stephen Jenkins, Isabelle Tutor, Michael R. Harrison, Angel Penning, Chandan Devireddy, Janice P. Lea, Amanda Fiebach, Claudia Merlin, Florian Rader, Suhail Dohad, Anne H. Tran, Kirin Bhatia, Naomi D.L. Fisher, Piotr Sobieszczyk, Ian Halliday, Tay Munson, Jason B. Lindsey, Steven B. Laster, Mathew Bunte, Anthony R Hart, Dana E. King, Jamie Hall, Kintur Sanghvi, Courtney Krathen, Luot Lewis, Ashley Willitts, Thomas M. Todoran, Jan Basile, Anthony Awkar, Casey Palmer, Anna Tecklenburg, John Schindler, John Pacella, Matthew F. Muldoon, MaryJo Albright, Tracy L. Nicholson, John M. Flack, Youseff Chami, Abdul Moiz Hafiz, Emily Starkey, Kristal Adams, Nelson L. Bernardo, Judith H. Veis, Hayder Hashim, Suman Singh, Donna Whitman, Rick Stouffer, Alan L. Hinderliter, Meghan Allen, Tatum Scholl, Pete Fong, James S. Gainer, Sherron Crook, Ellen Hatchcock, Debbie L. Cohen, Jay Giri, Taisei Kobayashi, Robin Neubauer, Suveeksha Naidu, Ajay J. Kirtane, Jai Radhakrishnan, Candido Batres, Suzanne Edwards, Matheen Khuddus, Suzanne Zentko, Abby Touchton, Marti Roberson, Michael J. Bloch, Abhilash Akinapelli, Lisa English, Bridget Neumann, Farrel Mendelsohn
Abstract
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.