Findings from the RADIANCE II randomised pivotal trial, presented at the 2022 Transcatheter Cardiovascular Therapeutics meeting (TCT, 16–19 September, Boston, USA), “confirm that ultrasound renal denervation lowers blood pressure across the spectrum of hypertension”.
RADIANCE II—results of which were described as “important data for the field” by discussants—was the first of two major renal denervation trials reporting results at TCT 2022, with the treatment having seen a renaissance following successive sham-controlled trials showing statistically significant and clinically meaningful in blood pressure.
The trial’s primary result was presented during a late-breaking clinical science session by Ajay Kirtane (Columbia University Irving Medical Center New York-Presbyterian Hospital, New York, USA). Kirtane reported that ultrasound renal denervation using the Paradise (Recor Medical) system was superior at lowering blood pressure when compared to a sham procedure.
Patients with hypertension (seated office BP ≥140/90 mmHg and <180/120 mmHg) on no more than two anti-hypertensive medications underwent a four-week observation time during which they were taken off all hypertension medications. Those who remained clinically stable after the observation period and whose blood pressure remained elevated with daytime ambulatory systolic blood pressure (ASBP) greater than or equal to 135/85 mmHg but less than 170/105 mmHg underwent anatomic screening with CTA/MRA. Those with qualifying renal artery anatomy proceeded to renal angiography, and if angiography re-confirmed suitability for ultrasound renal denervation, they were then randomised 2:1 to receive bilateral uRDN of the main and accessory (≥3 mm) renal arteries or a sham procedure.
Between March 2019 and May 2022, a total of 150 patients received the renal denervation procedure and 74 underwent a sham procedure. Baseline characteristics including ambulatory blood pressure and the number of anti-hypertensive medications were similar between both groups.
The primary efficacy endpoint was the change in ambulatory systolic blood pressure at two months. The change in ambulatory systolic blood pressure was -7.9 mmHg for the ultrasound renal denervation group compared to -1.8mmHg for the sham group. The between group difference was -6.3 mmHg (95%CI, -9.3 to -3.2, p<0.0001. In addition, the secondary efficacy endpoints of change in 24-hour, nighttime, home, and office systolic blood pressure showed statistically and clinically significant reductions (∆5-7 mmHg versus sham). There were also no major adverse events in either group through 30 days, Kirtane reported.
Kirtane’s presentation preceded the delivery of long-term results from the SYMPLICITY HTN-3 trial, assessing radiofrequency renal denervation using Medtronic’s Symplicity system.
Investigator Deepak Bhatt (Brigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, Boston, USA) commented that the findings indicate that durable blood pressure reductions with radiofrequency renal denervation in combination with maximal medical therapy can be safely achieved.
In the primary report of the SYMPLICITY HTN-3 trial, at six months, renal denervation was found to be safe but did not show any significant incremental blood pressure lowering benefit compared with a sham procedure. The present analysis reports long-term blood pressure changes in both initially treated renal denervation patients as well as in a composite control group consisting of sham-treated patients as well as sham-treated patients who crossed over to renal denervation after six months (but using blinded, pre-crossover data as the control).
Eligible patients had an x ≥160 mmHg and 24-hour ambulatory systolic blood pressure ≥135 mmHg. In addition, they were on stable, maximum tolerated doses of three or more antihypertension drugs.
A total of 535 patients at 88 sites in the USA were randomised 2:1 to renal denervation using the Symplicity Flex catheter (n=364) or sham control (n=171). Unblinding occurred after six months, and eligible control patients could crossover to renal denervation. For the 101 patients who crossed over and received renal denervation, their most recent blinded pre-crossover BP measurement and medication data were used as controls. Treatment differences were adjusted for baseline blood pressure.
At 12 months, renal denervation patients had significantly greater office systolic blood pressure reductions compared with sham control after crossover imputation (-18.9 mmHg vs -6.3 mmHg, p<0.0001, respectively). In addition, the number of antihypertension drugs were similar between patients in the RDN and control groups (4.7±1.4 vs. 4.7±0.9, p=0.22). The office systolic blood pressure reductions continued each year following the procedure, and at 36 months, the reduction in blood following renal denervation was -26.4 mmHg compared with -5.7 mmHg for the control group (p<0.0001). Similar results were observed in other measures of blood pressure (office diastolic blood pressure, 24 hour systolic and diastolic blood pressure).