PARIS — Renal denervation using ultrasound rather than radiofrequency ablation significantly reduced ambulatory blood pressure (BP) in the absence of antihypertensive agents compared with a sham procedure, reported investigators in a randomized trial.
The mean change in ambulatory systolic BP at 2 months, the primary endpoint, was –8.5 mm Hg (standard deviation [SD], 9.3 mm Hg) among 74 patients with mild to moderate hypertension randomly assigned to undergo renal denervation, compared with –2.2 mm Hg (SD, 10.0 mm Hg) in patients assigned to undergo a sham procedure, reported Laura Mauri, MD, from Brigham & Women's Hospital in Boston, Massachusetts, and colleagues in the RADIANCE-HTN SOLO trial.
The baseline adjusted difference between the groups was 6.3 mm Hg favoring renal denervation in an intention-to-treat analysis (P < .001).
"There were consistent reductions across the section of blood pressure measures at the office and home, a higher rate of blood pressure control in the absence of medications, and, importantly, no major adverse events within 30 days of the procedure," co-principal investigator Mauri reported here at the Congress of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR) 2018.
The study was simultaneously published online in The Lancet.
The device used in the study is the Paradise endovascular ultrasound ablation catheter (ReCor Medical). When deployed, the device emits a ring of ablative thermal energy to a depth of 1 to 6 mm to interrupt renal nerve traffic, with two to three ablations lasting 7 seconds each delivered to each main renal artery. The arterial wall is protected by water circulating through the device balloon.
The investigators enrolled patients with combined systolic-diastolic hypertension with an ambulatory BP (ABP) between 135/85 mm Hg and 170/105 mm Hg 4 weeks after they had stopped up to two antihypertensive agents. The patients also needed to have renal artery anatomy suitable for the procedure.
The patients were randomly assigned on a 1:1 basis to undergo denervation or a sham procedure consisting of renal angiography. Patients were required under the study to remain off antihypertensive medications for 2 months of follow-up, unless their BP surpassed prespecified criteria.
As noted, the trial met its primary efficacy endpoint of a change in daytime ambulatory systolic BP at 2 months.
In the per-protocol analysis, which excluded patients who resumed medication within 2 months of the procedure, patients treated with incomplete renal denervation, and those for whom 2-month ambulatory BP readings were not collected, the between-group difference adjusted for baseline BP was –8.2 mm Hg (P < .001).
For the intention-to-treat analysis, the between-group differences were significant across all secondary efficacy endpoints except nighttime ABP; the significant endpoints, all favoring renal denervation, were daytime ABP, 24-hour ABP, office BP, and home BP.
Additionally, significantly more patients treated with renal denervation were able to stay off antihypertensive drugs for control of both daytime ABP (20% vs 2%, P = .001) and 24-hour ABP (24% vs 3%, P < .001).
There were no major adverse events at 1 month in either study group: no deaths, acute renal failure within 30 days, embolic events resulting in end-organ damage, renal artery or other vascular complication requiring intervention within 30 days, or hypertensive crisis within 30 days. In addition, no new cases of renal artery stenosis greater than 50% occurred in either group at 2 months.
Procedure-related pain lasting longer than 2 days occurred in 11% of patients in each group.
The investigators will follow patients through 3 years to assess long-term safety and efficacy. In addition, a parallel blinded sham-controlled trial of renal denervation in patients with resistant hypertension (RADIANCE-HTN-TRIO) is enrolling patients, Mauri said.
In an interview, theheart.org | Medscape Cardiology asked Mauri how renal denervation compared to medical control of BP in the patients enrolled.
She replied that following the 4-week washout period before randomization, patients experienced an approximately 10–mm Hg increase in office systolic BP, "and with renal denervation we actually saw a greater than 10 mm decrease in office systolic BP."
In an editorial accompanying the study, Sverre E. Kjeldsen, MD, from the University of Oslo, Norway, and Murray D. Esler, PhD, from the Baker Heart & Diabetes Institute in Melbourne, Australia, comment that the results of RADIANCE-HTN SOLO and the SPYRAL trial, also presented here at EuroPCR 2018 and published in The Lancet, "open a new chapter in renal denervation research."
"What is the clinical benefit? The 6.3 mm Hg reduction in daytime ambulatory systolic blood pressure generally corresponds to twice as much of a reduction in office systolic blood pressure, which in turn corresponds to the benefit of one effective antihypertensive drug. But, as shown in RADIANCE-HTN SOLO, there might be responders and non-responders, and some patient subgroups might benefit more than others. The patients who are likely to receive the most benefit should be identified, which will be possible with further research," they write.
They noted that renal denervation still needs to be evaluated in terms of sustained efficacy and safety, as well as its potential benefits in preventing cardiovascular, renal, and neurovascular complications from prolonged hypertension.
The editorialists caution that although the investigators attempted to control for the Hawthorne effect — the tendency of trial participants who know they are being observed to change their behavior — they were unable to completely rule it out because they relied on patient-reported use of antihypertensive agents during follow-up.
In the late-breaking abstract session where Mauri presented the data, invited discussant Robert Byrne, PhD, from the German Heart Center Munich, commented that "it's great to have more sham-controlled data available in this space."
"But we need to realize that sometimes the quality metrics for sham-controlled trials need to be particularly high because certain patients are exposed to risk without any potential for benefit," he continued.
He noted that the procedural times significantly differed between the groups — a mean of 72 minutes from arterial sheath insertion to removal in the renal denervation group vs 38 minutes in the sham-control group (P < .001) — and asked whether patients had been surveyed formally after the procedure to determine how effective the blinding actually was.
Mauri replied that the investigators used both the Bang and James indices to assess blinding in clinical trials, "and we saw that there was very consistent blinding both at discharge and at 2 months."
She noted that the Bang index, which is more sensitive than the James index for blinding between groups, showed significantly better blinding in the sham group at discharge, but no differences at 2 months.
The study was supported by ReCor. Mauri disclosed personal fees from the company and from Medtronic. Byrne has disclosed serving as a speaker or a member of a speakers bureau for B. Braun Melsungen AG, BIOTRONIK, and Boston Scientific and research grants from Heart Flow and Boston Scientific. Kjeldsen has received ad hoc honoraria for lecturing from Bayer, Merck & Co, Sanofi, and Takeda and honoraria from Takeda for study committee work within the past 3 years, all outside the area of work commented on here. Esler is a member of Medtronic's Renal Denervation Advisory Board and receives honoraria from Medtronic.
Congress of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR) 2018. Late-breaking abstract. Presented May 23, 2018.
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