Will Renal Denervation Prove to Be a Viable Treatment Option for Blood Pressure That Is Treated but Not Controlled?
Michael J. Bloch, MD
Associate Professor, University of Nevada School of Medicine
Medical Director, Vascular Care, Renown Institute for Heart and Vascular Health
President, Blue Spruce Medical Consultants, PLLC
Bloch MJ. Will renal denervation prove to be a viable treatment option for blood pressure that is treated but not controlled? Consultant360. Published online July 28, 2021.
Dr Bloch emphasizes that RDN remains an unapproved investigational procedure in the United States. Dr Bloch has served as a primary investigator and paid consultant for Recor Medical, the sponsor of the RADIANCE-HTN TRIO study. He has also served as a paid consultant for Medtronic, which has sponsored trials with radiofrequency RDN.
Incomplete adherence, high pill burden, and therapeutic inertia contribute to the frustratingly low blood pressure (BP) control rates in the United States. As such, there is considerable interest in developing nonpharmacological therapies to help improve BP control. Among the most studied is endovascular renal denervation (RDN). The premise behind RDN is that increased sympathetic traffic to and from the kidney is a significant contributor to poorly controlled BP, even in the setting of antihypertensive medications. Using endovascular techniques, a catheter with an energy source is advanced into the renal artery and the renal nerves, both efferent and afferent, are ablated by applying energy across the arterial wall to the perivascular space where these nerves are found. Both ultrasound and radiofrequency energy have been extensively studied.
As part of this clinical trial program, the RADIANCE-HTN TRIO study was a randomized, international, multicenter, blinded, sham-controlled study of patients aged 18 to 75 years with office BP of at least 140/90 mm Hg despite taking 3 or more antihypertensive medications.1 Participants who met these initial criteria were switched to a once daily, fixed-dose, single-pill combination of an angiotensin receptor blocker (ARB), a calcium channel blocker, and a thiazide type diuretic. After 4 weeks of this standardized therapy, participants underwent 24-hour ambulatory BP monitoring and were eligible for randomization if mean daytime ambulatory BP remained at least 135/85 mm Hg despite this 3-drug combination. Additional inclusion criteria required a glomerular filtration rate of at least 40 mL/min/1.73 m2 with suitable renal artery anatomy and no evidence of renal artery stenosis. Participants who met these criteria were randomly assigned to receive endovascular ultrasound RDN or a sham procedure. All participants were instructed to remain on the 3-drug fixed combination tablet, and the primary efficacy endpoint was change in daytime ambulatory systolic BP from baseline to 2 months.
Overall, 136 participants were randomly assigned (69 to RDN and 67 to sham). Adherence to background medical therapy was high in both groups (82%) but not complete. In the intention- to-treat analysis, despite more participants in the sham group receiving rescue antihypertensive medications, participants in the RDN group had greater reduction in mean daytime ambulatory systolic BP than those in the sham group, with a mean between group difference of -4.5 mm Hg at 2 months. In the perprotocol analysis, the difference was -5.4 mm Hg. The mean difference in office systolic BP was -7.0 mm Hg. There was no difference in safety outcomes between the groups.
Although the reductions in BP with RDN were rather modest, this level of BP reduction is generally consistent with the addition of 1 to 2 medications, and a review of observational studies would suggest that it is clinically significant and would lead to a measurable reduction in cardiovascular events if sustained.2 This study adds to a growing list of studies with both ultrasound and radiofrequency RDN demonstrating clinically significant reductions in BP across a spectrum of background antihypertensive medications from 0 to at least 3.3-8
BP control rates remain stubbornly low in the United States, despite the widespread availability of safe, effective, and inexpensive medications. When providers are faced with patients with uncontrolled hypertension, some action must be taken. But, given low rates of long-term adherence to antihypertensive medications, it is clear that at least to date a paradigm that relies solely on adding additional medication has not been effective and is not what all patients desire. Since RDN is a one-time, adherence-independent intervention, it may prove to be a valuable clinical tool in patients whose BP has been treated but not controlled and who prefer to undergo a procedure as opposed to adding additional medication, as long as future studies continue to demonstrate safety and durability of RDN.
1. 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 randomized, multicentre, single-blind, sham-controlled trial. Lancet. 2021;397(10293):2476-2486. https://doi.org/10.1016/s0140-6736(21)00788-1
2. Blood Pressure Lowering Treatment Trialists' Collaboration. Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis. Lancet. 2021;397(10285):1625-1636. https://doi.org/10.1016/s0140-6736(21)00590-0
3. 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(10137):2335-2345. https://doi.org/10.1016/s0140-6736(18)31082-1
4. Kandzari DE, Böhm M, Mahfoud F, et al; SPYRAL HTN-ON MED Trial Investigators. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomized trial. Lancet. 2018;391(10137):2346-2355. https://doi.org/10.1016/s0140-6736(18)30951-6
5. Böhm M, Kario K, Kandzari DE, et al; SPYRAL HTN-OFF MED Pivotal Investigators. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre randomised, sham-controlled trial. Lancet. 2020;395(10234):1444-1451. https://doi.org/10.1016/s0140-6736(20)30554-7
6. Azizi M, Schmieder RE, Mahfoud F, et al; RADIANCE-HTN Investigators. Six-month results of treatment-blinded medication titration for hypertension control following randomization to endovascular ultrasound renal denervation or a sham procedure in the RADIANCE-HTN SOLO trial. Circulation. Published online March 17, 2019. https://doi.org/10.1161/circulationaha.119.040451
7. Azizi M, Daemen J, Lobo MD, et al; RADIANCE-HTN Investigators. 12-month results from the unblinded phase of the RADIANCE-HTN SOLO trial of ultrasound denervation. JACC Cardiovasc Interv. 2020;13(24):2922-2933. https://doi.org/10.1016/j.jcin.2020.09.054
8. Mahfoud F, Bloch MJ, Azizi M, et al. Changes in blood pressure after crossover to ultrasound renal denervation in patients initially treated with sham in the RADIANCE-HTN SOLO Trial. EuroInterventions. 2021;EIJ-D-21-00295. https://doi.org/10.4244/eij-d-21-00295