Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO Trials
Ajay J. Kirtane, Andrew Sharp, Felix Mahfoud, Naomi D.L. Fisher, Roland E. Schmieder, Joost Daemen, Melvin D. Lobo, Philipp Lurz, Jan Basile, Michael J. Bloch, Michael A. Weber, Manish Saxena, Yale Wang, Kintur Sanghvi, J. Stephen Jenkins, Chandan Devireddy, Florian Rader, Philippe Gosse, Marc Sapoval, Neil C. Barman, Lisa Claude, Dimitri Augustin, Lisa Thackeray, Christopher M. Mullin, Michel Azizi, RADIANCE Investigators and Collaborators, Candace K. McClure, Glenn M. Chertow, Venita Chandra, Harold L. Dauerman, Thomas Kahan, Steven Ullery, Nirat Beohar, Ozgen Dogan, M Mokrzycki, Scott Mullaney, Björn Redfors, Huseng Vefali, J. Dawn Abbott, Andreas Loening, Ron Zagoria, Nedaa Skeik, Richard Bae, Amy McMeans, JoAnne Goldman, Rose Peterson, Desmond Jay, Robert S. Schwartz, John P. Reilly, Micheal Cash, Isabelle Tutor, Michael R. Harrison, Shannon Williams, Maria Jarvis, Angel Penning, Janice P. Lea, Amanda Fiebach, Claudia Merlin, Bryan J. Wells, Suhail Dohad, Anne H. Tran, Kirin Bhatia, H. Mike Kim, Mohammad A Rashid, Ronald G. Victor, Piotr Sobieszczyk, Ian Halliday, Tay Munson, Laura Mauri, Alex Smith, Laura Aseltine, Jonathan S. Williams, Jason B. Lindsey, Steven B. Laster, Mathew Bunte, Anthony R Hart, Dana E. King, Jamie Hall, Josh Costello, Courtney Krathen, Luot Lewis, Andrew McElvarr, Ashley Willitts, Thomas M. Todoran, Eric R. Powers, Casey Palmer, Emily Hodskins, Vijay Paladugu, 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
Abstract
Importance: Ultrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency of the uRDN effect across the HTN spectrum is clinically important. Objective: To characterize the effectiveness and safety of uRDN vs a sham procedure from individual patient-level pooled data across uRDN trials including either patients with mild to moderate HTN on a background of no medications or with HTN resistant to standardized triple-combination therapy. Data Sources: A Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN SOLO and TRIO) and A Study of the ReCor Medical Paradise System in Stage II Hypertension (RADIANCE II) trials. Study Selection: Trials with similar designs, standardized operational implementation (medication standardization and blinding of both patients and physicians to treatment assignment), and follow-up. Data Extraction and Synthesis: Pooled analysis using individual patient-level data using linear regression models to compare uRDN with sham across the trials. Main Outcomes and Measures: The primary outcome was baseline-adjusted change in 2-month daytime ambulatory systolic BP (dASBP) between groups. Results: A total of 506 patients were randomized in the 3 studies (uRDN, 293; sham, 213; mean [SD] age, 54.1 [9.3]; 354 male [70.0%]). After a 1-month medication stabilization period, dASBP was similar between the groups (mean [SD], uRDN, 150.3 [9.2] mm Hg; sham, 150.8 [10.5] mm Hg). At 2 months, dASBP decreased by 8.5 mm Hg to mean (SD) 141.8 (13.8) mm Hg among patients treated with uRDN and by 2.9 mm Hg to 147.9 (14.6) mm Hg among patients treated with a sham procedure (mean difference, -5.9; 95% CI, -8.1 to -3.8 mm Hg; P < .001 in favor of uRDN). BP decreases from baseline with uRDN vs sham were consistent across trials and across BP parameters (office SBP: -10.4 mm Hg vs -3.4 mm Hg; mean difference, -6.4 mm Hg; 95% CI, -9.1 to -3.6 mm Hg; home SBP: -8.4 mm Hg vs -1.4 mm Hg; mean difference, -6.8 mm Hg; 95% CI, -8.7 to -4.9 mm Hg, respectively). The BP reductions with uRDN vs sham were consistent across prespecified subgroups. Independent predictors of a larger BP response to uRDN were higher baseline BP and heart rate and the presence of orthostatic hypertension. No differences in early safety end points were observed between groups. Conclusions and Relevance: Results of this patient-level pooled analysis suggest that BP reductions with uRDN were consistent across HTN severity in sham-controlled trials designed with a 2-month primary end point to standardize medications across randomized groups. Trial Registration: ClinicalTrials.gov Identifier: NCT02649426 and NCT03614260.