Patient-Level Pooled Analysis of Endovascular Ultrasound Renal Denervation or a Sham Procedure at 6 Months Following Medication Escalation: The RADIANCE Clinical Trial Program

Abstract

Background: The RADIANCE-HTN SOLO, RADIANCE-HTN TRIO, and RADIANCE II randomized, sham-controlled trials independently met their primary endpoint of a greater reduction in daytime ambulatory systolic blood pressure (SBP) at 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN vs. sham at 6 months, following the blinded addition of antihypertensive treatments (AHT), we pooled individual patient data across these three similarly designed trials. Methods: Patients with mild-to-moderate hypertension on no AHT or with hypertension resistant to standardized combination triple AHT were randomized to uRDN (n=293 in total) vs. sham (n=213 in total); they were to remain off added AHT throughout 2 months of follow-up unless specified BP criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mmHg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mmHg under blinding to initial treatment assignment. Six-month outcomes included (1) baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP, (2) change in AHT, and (3) 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 aged 54.1±9.3 years with baseline daytime ambulatory/home/office SBP of 150.5±9.8/151.0±12.4/155.5±14.4 mmHg, 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 vs. sham patients (P=0.001). While 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 mmHg (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 mmHg (-6.8, -4.0; P<0.001) and -5.2 mmHg (-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 RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN vs. sham at 6 months, with fewer added AHT.