Full results of the RADIANCE II trial, showing significant reductions in systolic blood pressure with ultrasound renal denervation in patients with hypertension, have been published, along with a pooled analysis of all three RADIANCE trials showing similar results across a larger patient group.
“The three trials together, including data from more than 500 patients, showed very consistent results demonstrating that ultrasound renal denervation can safely lower blood pressure across a range of patients with varying degrees of hypertension severity,” Michel Azizi, MD, Université Paris Cité, France, told theheart.org | Medscape Cardiology.
“These results reinforce the role of the ultrasound renal denervation system as an adjunctive therapy for hypertension treatment, in addition to medications and lifestyle modification,” he added.
The RADIANCE-II trial was published in JAMA on February 28. It was previously presented at last year’s Transcatheter Cardiovascular Therapeutics meeting.
The pooled analysis of the three RADIANCE trials, which include RADIANCE II, RADIANCE-SOLO, and RADIANCE TRIO, was simultaneously published in JAMA Cardiology.
Azizi noted that the results of the three studies are in line with the new 2023 consensus statement of the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions for renal denervation in hypertension published in the European Heart Journal recently.
That consensus statement proposed that “[r]enal denervation is an adjunct treatment option in uncontrolled resistant hypertension, confirmed by ambulatory blood pressure measurements, despite best efforts at lifestyle and pharmacological interventions. Renal denervation may also be used in patients who are unable to tolerate antihypertensive medications in the long term.”
But in an editorial accompanying the current pooled analysis, published in JAMA Cardiology, three hypertension experts say there are still questions to be answered on the procedure and that longer-term data are needed.
All three RADIANCE trials used the Paradise catheter device (ReCor Medical), which uses ultrasound energy to disrupt renal sympathetic nerve activity.
The RADIANCE-HTN SOLO study, which enrolled patients with mild to moderate hypertension who were not taking medication, and RADIANCE-HTN TRIO, which included patients with hypertension despite fixed-dose, single-pill, triple-antihypertensive therapy, both showed significant reductions in blood pressure with the procedure.
The larger pivotal RADIANCE-II trial included 224 patients with uncontrolled hypertension who were withdrawn from receiving background antihypertensive medications and were then randomly assigned in a 2:1 ratio to undergo ultrasound renal denervation or a sham procedure. They were then maintained without antihypertensive medications until assessment of change in daytime ambulatory systolic blood pressure at 2 months, which was the primary endpoint.
Results showed that among patients in the active group, the mean reduction in daytime ambulatory systolic blood pressure was -7.9 mm Hg, vs -1.8 mm Hg in the sham group, at 2 months.
“The between-group difference of -6.3 mm Hg was highly statistically significant (P < .0001) and clinically pertinent. In addition, highly consistent average reductions in 24-hour, home, and office systolic blood pressure efficacy endpoints at 2 months were achieved,” Azizi noted.
“Interestingly, the blood pressure reduction was already present as early as 1 month after the procedure and was consistent over the 24-hour circadian cycle, with similar blood pressure decreases during daytime, nighttime, and early-morning phase,” he added.
The effect on daytime ambulatory systolic blood pressure was consistent across all prespecified subgroups, and no major adverse events were observed.
The pooled analysis of the three trials involved a total of 506 patients who were randomly assigned to undergo ultrasound renal denervation (n = 293) or sham (n = 213). After a 1-month medication stabilization period, daytime ambulatory systolic blood pressure was similar between the groups, but by 2 months, it had decreased by 8.5 mm Hg to a mean of 141.8 mm Hg in the active treatment group and by 2.9 mm Hg to 147.9 mm Hg in the sham treatment group (mean difference, −5.9 mm Hg; P < .001).
Decreases in blood pressure from baseline with the procedure were consistent across trials and across office and home measurements and prespecified subgroups.
Factors that independently predicted a greater response to the procedure were higher baseline blood pressure and heart rate and the presence of orthostatic hypertension.
“Orthostatic hypertension is supposed to be a sympathetically mediated phenomenon and thus could be a potential marker of a larger blood pressure response to ultrasound renal denervation,” Azizi said.
No differences in early safety endpoints were observed between groups.
Longer-Term Data Needed
In their editorial, Clyde Yancy, MD, Northwestern University Feinberg School of Medicine, Chicago, Gregg Fonarow, MD, University of California, Los Angeles, and Patrick O’Gara, MD, Brigham and Women’s Hospital, Boston, call for longer-term data on renal denervation.
They point out that these studies report a modest reduction in systolic blood pressure over sham control at 2 months, and although safety appears reasonable, follow-up has been too short to determine clinical outcomes, and there have been numerically more events among patients treated with the ultrasound procedure than among sham control individuals.
“In anticipation of possible near-term approval from the US Food and Drug Administration for renal denervation, there must be an insistence on longer-term clinical outcomes and safety data,” the editorialists urge.
“Disease-modifying, readily available, and easily affordable medical therapies for hypertension are ubiquitous and set a high bar for any new therapeutic. The magnitude of blood pressure reduction attributable to ultrasound renal denervation approximates that of the addition of a single other drug class and is likely less than the addition of mineralocorticoid receptor antagonist therapy,” they note.
“Similarly, the individual and aggregate benefit of lifestyle modification equates and likely exceeds the reduction of blood pressure reduction attributable to ultrasound renal denervation. Nevertheless, many patients do not respond adequately to these combined efforts, and new pathways to blood pressure control are welcomed, provided efficacy and safety have been established,” they say.
They add that questions regarding patient selection, anatomic or physiologic barriers to denervation, durability of the blood pressure response, and operator or institutional requirements will need to be addressed.
“Additional choices in the management of hypertension meet an important public health objective but use of ultrasound renal denervation ― like all other antihypertensive therapies ― must follow a supportive evidence base and fold into a more comprehensive disease-management algorithm that emphasizes lifestyle modification and known standards of care for medical therapy,” they conclude.
Azizi said that long-term follow-up is planned. He noted that “RADIANCE-HTN SOLO (off-medication) and TRIO (on triple combination pill) trials have both shown the long-term durability of the blood pressure lowering effect of ultrasound renal denervation.”
Six-month results from the RADIANCE TRIO trial were published late last year, and follow-up has now reached 36 months in the SOLO trial.
Azizi has received grants from the European Horizon 2020 program; grants and nonfinancial support from ReCor Medical and Idorsia; and personal fees from Alnylam Pharmaceuticals, Poxel SA, Medtronic, and Novartis. Yancy reports spousal employment at Abbott Laboratories. Fonarow has received personal fees from Abbott Laboratories, Amgen, AstraZeneca, Bayer, Cytokinetics, Edwards, Eli Lilly, Janssen, Medtronic, Merck, Novartis, and Pfizer outside the submitted work.
JAMA. Published online February 28, 2023. Abstract
JAMA Cardiol. Published online February 28, 2023. Full text, Editorial
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