Effects of Renal Denervation vs Sham in Resistant Hypertension After Medication Escalation
Michel Azizi, Felix Mahfoud, Michael A. Weber, Andrew Sharp, Roland E. Schmieder, Philipp Lurz, Melvin D. Lobo, Naomi D.L. Fisher, Joost Daemen, Michael J. Bloch, Jan Basile, Kintur Sanghvi, Manish Saxena, Philippe Gosse, J. Stephen Jenkins, Terry Levy, Alexandre Persu, Benjamin Kably, Lisa Claude, Helen Reeve-Stoffer, Candace K. McClure, Ajay J. Kirtane, RADIANCE-HTN Investigators, Christopher M. Mullin, Lisa Thackeray, Glenn M. Chertow, Thomas Kahan, Harold L. Dauerman, Steven Ullery, J. Dawn Abbott, Andreas Loening, Ron Zagoria, John Costello, Courtney Krathan, Luot Lewis, Andrew McElvarr, John P. Reilly, Michael Cash, Shannon Williams, Maria Jarvis, Pete Fong, Cheryl L. Laffer, James S. Gainer, Mark Robbins, Sherron Crook, Sarita Maddel, David H. Hsi, Scott D. Martin, Edward L. Portnay, Maryanne Ducey, Suzanne Rose, Elizabeth DelMastro, Sripal Bangalore, Stephen Williams, Stanley Cabos, Carolina Rodríguez Álvarez, Thomas M. Todoran, Eric R. Powers, Emily Hodskins, Vijay Paladugu, Anna Tecklenburg, Chandan Devireddy, Janice P. Lea, Bryan J. Wells, Amanda Fiebach, Claudia Merlin, Florian Rader, Suhail Dohad, H. Mike Kim, Mohammad H. Rashid, Josephine Abraham, Theophilus Owan, Anu Abraham, Iran Lavasani, Hailey Neilson, David A. Calhoun, Thomas McElderry, William Maddox, Suzanne Oparil, Sheila Kinder, Jai Radhakrishnan, Candido Batres, Suzanne Edwards, Joseph Garasic, Doug Drachman, Randy Zusman, Kenneth Rosenfield, Danny Do, Matheen Khuddus, Suzanne Zentko, James O’Meara, Ilie Barb, Abby Foster, Alice Boyette, Yale Wang, Desmond Jay, Nedaa Skeik, Robert S. Schwartz, Rose Peterson, Jo Anne Goldman
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.