TY - JOUR
T1 - Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO Trials
AU - the RADIANCE Investigators and Collaborators
AU - Kirtane, Ajay J.
AU - Sharp, Andrew S.P.
AU - Mahfoud, Felix
AU - Fisher, Naomi D.L.
AU - Schmieder, Roland E.
AU - Daemen, Joost
AU - Lobo, Melvin D.
AU - Lurz, Philipp
AU - Basile, Jan
AU - Bloch, Michael J.
AU - Weber, Michael A.
AU - Saxena, Manish
AU - Wang, Yale
AU - Sanghvi, Kintur
AU - Jenkins, James Stephen
AU - Devireddy, Chandan
AU - Rader, Florian
AU - Gosse, Philippe
AU - Sapoval, Marc
AU - Barman, Neil C.
AU - Claude, Lisa
AU - Augustin, Dimitri
AU - Thackeray, Lisa
AU - Mullin, Christopher M.
AU - Azizi, Michel
AU - McClure, Candace K.
AU - Chertow, Glenn
AU - Dauerman, Harold
AU - Kahan, Thomas
AU - Ullery, Steven
AU - Chandra, Venita
AU - Beohar, Nirat
AU - Dogan, Ozgen
AU - Mokrzycki, Michelle
AU - Mullaney, Scott
AU - Redfors, Bjorn
AU - Vefali, Huseng
AU - Abbott, J. Dawn
AU - Loening, Andreas
AU - Zagoria, Ron
AU - Skeik, Nedaa
AU - Bae, Richard
AU - McMeans, Amy
AU - Goldman, Jo Anne
AU - Peterson, Rose
AU - Tutor, Isabelle
AU - Harrison, Michael
AU - Benzuly, Keith
AU - Paparello, James
AU - Fintel, Dan
N1 - Publisher Copyright:
© 2023 American Medical Association. All rights reserved.
PY - 2023/5/10
Y1 - 2023/5/10
N2 - 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.
AB - 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.
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U2 - 10.1001/jamacardio.2023.0338
DO - 10.1001/jamacardio.2023.0338
M3 - Article
C2 - 36853627
AN - SCOPUS:85158867416
SN - 2380-6583
VL - 8
JO - JAMA cardiology
JF - JAMA cardiology
IS - 5
M1 - JOI230007
ER -