Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO Trials

• Type of Material: Article
• Authors: Ajay J Kirtane, Columbia University Irving Medical Center; Andrew SP Sharp, University Hospital of Wales; Felix Mahfoud, Universitätsklinikum des Saarlandes Medizinische Fakultät der Universität des Saarlandes; Naomi DL Fisher, Harvard Medical School; Roland E Schmieder, Universitätsklinikum Erlangen; Joost Daemen, Erasmus MC; Melvin D Lobo, Barts and The London School of Medicine and Dentistry; Philipp Lurz, Universität Leipzig; Jan Basile, Medical University of South Carolina; Michael J Bloch, University of Nevada School of Medicine; Michael A Weber, SUNY Downstate Health Sciences University; Manish Saxena, Barts and The London School of Medicine and Dentistry; Yale Wang, Minneapolis Heart Institute; Kintur Sanghvi, DEBORAH Heart and Lung Center; Stephen J Jenkins, Ochsner Medical Center - New Orleans; Chandan Devireddy, Emory University; Florian Rader, Cedars-Sinai Medical Center; Philippe Gosse, Hopital Saint-Andre; Marc Sapoval, Université Paris Cité; Neil C Barman, ReCor Medical; Lisa Claude, ReCor Medical; Dimitri Augustin, ReCor Medical; Lisa Thackeray, NAMSA; Christopher M Mullin, NAMSA; Michel Azizi, Université Paris Cité
• Language: English
• Date: 2023-05-10
• Publisher: JAMA Cardiology.
• Publication Version: Final Published Version
• Copyright Statement: 2023 Kirtane AJ et al. JAMA Cardiology.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1001/jamacardio.2023.0338
• Title of Journal or Parent Work: JAMA Cardiology
• Volume: 8
• Issue: 5
• Start Page: 464
• End Page: 473
• Grant/Funding Information: The study was funded by ReCor Medical Inc.
• Keywords: Hypotension; Male; Kidney; Middle Aged; Treatment Outcome; Humans; Antihypertensive Agents; Hypertension; Sympathectomy
• Research Categories: Health Sciences, Medicine and Surgery

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.