Renal denervation (RDN) is an adjunct treatment for hypertension (HTN) that involves catheter ablation of the sympathetic plexus in the adventitia of the renal arteries using radiofrequency (RF) or ultrasound waves. The first sham-controlled RDN trial, the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial, used RF RDN and failed to demonstrate a benefit of RDN compared with a sham procedure in lowering blood pressure (BP), which might have been because of limitations in trial design with frequent medication changes during the trial, issues with medication adherence among trial participants, and inadequate operator experience at multiple sites included.¹ However, there have been subsequent sham-controlled trials of RDN whose findings showed the consistent clinical benefit of RDN in lowering BP compared with a sham procedure.^2-6

The RADIANCE II (A Study of the ReCor Medical Paradise System in Stage II Hypertension) was a multicenter study that compared the safety and efficacy of ultrasound-based RDN with sham control among patients with stage II HTN (i.e., BP ≥135/85 and <170/105 mm Hg).³ Patients (n = 224) 18-75 years of age with a history of HTN treated with medical therapy (up to two antihypertensive agents) were randomized to either RDN (n = 150) or a sham control (n = 74). Antihypertensive agents were discontinued 4 weeks before randomization. Renal nerve ablation was performed in the RDN group after assessing the renal angiogram with the Paradise Ultrasound RDN System (ReCor Medical Inc., Palo Alto, California). All patients remained off antihypertensive agents until 2 months after randomization unless office BP ≥180/110 mm Hg or home BP ≥170/105 mm Hg was noted. Before antihypertensive agent washout, baseline office BP was 156/102 mm Hg and ambulatory BP was 144/88 mm Hg. At 2-month follow-up, daytime ambulatory systolic BP was lower in the RDN group than in the sham group (-7.9 vs. -1.8 mm Hg [95% confidence interval, -9.3 to -3.2 mm Hg; p < 0.0001]). There were no short-term safety concerns. Renal artery stenosis and all-cause 30-day death rates were 0%.

The RADIANCE II data demonstrated the benefit of ultrasound-based RDN therapy in lowering BP (without antihypertensive agents) versus a sham procedure in the short term with no significant safety events.³ The reduction in BP seen in these results was similar to that noted in the results of the SPYRAL HTN-OFF MED (Investigation of Catheter-Based Renal Denervation in Patients With Uncontrolled Hypertension in the Presence of Antihypertensive Medications), RADIANCE-HTN SOLO (A Study of the Recor Medical Paradise System in Clinical Hypertension), and RADIANCE-HTN TRIO (Ultrasound Renal Denervation for Hypertension Resistant to a Triple Medication Pill) trials at 6 months among RDN versus sham groups.^2-4,6 BP reductions were similar to those expected with a single antihypertensive agent.

RDN is currently used as an adjunct to medical therapy and lifestyle modifications. However, it may be a reasonable alternative to medical treatment, particularly when noncompliance with medications is concerned. Longitudinal data are needed to understand the long-term benefits of this therapy. Finally, there remain a few unknowns, such as preprocedural predictors of patient responsiveness to RDN (e.g., which patients may benefit and markers of successful denervation) that should be investigated in future trials.

References

1. Bhatt DL, Kandzari DE, O'Neill WW, et al.; SYMPLICITY HTN-3 Investigators. A controlled trial of renal denervation for resistant hypertension. N Engl J Med 2014;370:1393-401.
2. Azizi M, Sanghvi K, Saxena M, et al.; RADIANCE-HTN investigators. Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial. Lancet 2021;397:2476-86.
3. Azizi M, Saxena M, Wang Y, et al.; RADIANCE II Investigators and Collaborators. Endovascular ultrasound renal denervation to treat hypertension: the RADIANCE II randomized clinical trial. JAMA 2023;329:651-61.
4. Azizi M, Schmieder RE, Mahfoud F, et al.; RADIANCE-HTN Investigators. Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial. Lancet 2018;391:2335-45.
5. Azizi M, Sharp ASP, Fisher NDL, et al.; RADIANCE Investigators. Patient-level pooled analysis of endovascular ultrasound renal denervation or a sham procedure 6 months after medication escalation: the RADIANCE clinical trial program. Circulation 2024;149:747-59.
6. Townsend RR, Mahfoud F, Kandzari DE, et al.; SPYRAL HTN-OFF MED Trial Investigators. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet 2017;390:2160-70.