Updates from TCT 2023: Renal Denervation

In this video, Michael J. Bloch, MD, discusses hypertension and a patient-level pooled analysis of ultrasound renal denervation in the sham-controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO trials. Dr Bloch discussed these trials at TCT 2023.

Additional Resource:

Kirtane AJ, Sharp ASP, Mahfoud F, et al; RADIANCE Investigators and Collaborators. Patient-level pooled analysis of ultrasound renal denervation in the sham-controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO Trials. JAMA Cardiol. 2023;8(5):464-473. doi:10.1001/jamacardio.2023.0338

TRANSCRIPTION:

Hello. My name is Dr Michael Bloch.

I'm a hypertension and vascular medicine specialist from Reno, Nevada, and I just returned from the TCT meetings in San Francisco where we saw an awful lot of data being presented about renal denervation.

I want to share with you some of that data, in fact, a trial result that I shared myself at this meeting. Before I go into the results, though, I do just want to highlight the fact that I am a consultant for a couple of different companies that make medical devices around hypertension, including ReCor, which makes the Paradise catheter I'm going to be talking about today. I also want to remind you that renal denervation is investigational in the United States, and not yet approved in this country.

 So, what I'm going to share with you today is data from the Paradise Ultrasound Renal Denervation System. This is a percutaneous system where we put an ultrasound catheter in the renal arteries and use ultrasound energy to ablate the afferent and efferent sympathetic nerves that travel back and forth from the CNS to the kidney. We have used this in multiple clinical trials, and in fact, this endovascular ultrasound renal denervation has been shown to consistently lower blood pressure in patients with both mild to moderate hypertension in studies that were known as Radiance Solo and Radiance 2, and in patients with resistant hypertension in the Radiance TRIO trial. All three of these were international prospective randomized sham control studies.

What I presented last week, and I'll be talking to you about today, is the data from the crossover arms of those three clinical trials. So as part of the scheme for the studies, as part of the methodology, patients who were initially randomized to sham, after six months were unblinded, they were treated with as-needed antihypertensive medications to try to get to control, and after a year or so, if their blood pressure was still not controlled and they chose to do so, they could get open label renal denervation done. This was true in all three of those studies. So the objective of this current analysis was to assess the change in daytime ambulatory blood pressure and medication requirements from individual patient level pool data across these three studies, all from the sham group who then crossed over to receive ultrasound renal denervation.

So, to date, 92 patients who were originally randomized to sham in these three studies have crossed over to receive renal denervation in the RADIANCE program, about evenly split between the three studies. The average time from their initial randomization to sham to when they requalified to get renal denervation and had the procedure performed was nearly two years, it was 23.8 months.

In general, these patients were relatively young, their mean age was in the 50s, about a third of them were female, and about three-quarters of them were White, but other racial and ethnic minorities were included. A small number had diabetes and a qualification to be in the study was having a GFR of greater than 40, so these patients generally had well-maintained kidney function. At the time that they were requalified as having poorly controlled blood pressure and requalified to be considered for renal denervation, on average they were on about 1.8 medications and their average office blood pressure was about 150 over 95. As I mentioned, the primary endpoint in all of these studies was the change in ambulatory blood pressure from before the procedure to after the procedure ambulatory blood pressure is always a little bit lower than office blood pressure and their mean ambulatory just before the procedure was about 146 over 91. And then we reassessed ambulatory blood pressure at two months, at six months, and at 12 months in these patients. And what we found was at two months, which was generally considered the primary endpoint for this study, there was no change in the number of medications that these patients were taking and yet there was an additional 10-millimeter reduction in systolic blood pressure and a 6.5-millimeter reduction in diastolic blood pressure. That was maintained out at six months, still a 10-millimeter reduction in daytime ambulatory, and then again at 12 months when we once again saw a 9.6-millimeter reduction in daytime ambulatory blood pressure. A good number of these patients had ambulatory blood pressures done at all three of those time points, two months, six months, and 12 months, and all of them showed really durable reductions in blood pressure of about 10 millimeters. At daytime ambulatory of 10-millimeters, if we look at observational studies that would be associated, if it was maintained for a number of years, would be associated with an approximately 20% reduction in cardiovascular events.

In terms of safety in general, both in this analysis and in the previous reports of ultrasound renal denervation, we've had very few safety issues of any concern. About 16% of patients did have some pain after the procedure, procedures were generally done under conscious sedation, but some patients did have continued pain. Other than that, there are a couple of access complications, but no changes in renal function, no new renal artery stenosis, and in general, very few safety issues.

So, there were certainly some limitations to this analysis. Patients and investigators were unblinded, there was no control group, background medication use was not standardized, and adherence was not measured. So these are all limitations when we start talking about a research study, but in actuality, these mimic the real world, and one of the reasons I was very interested in looking at this data, is that I think it looks a lot like the type of patients that we may consider renal denervation in, and the type of setting that those patients will be in if and when it's approved. So, I think it really does provide us with some real-world data about the utility of renal denervation.

So, in conclusion, in patients initially randomized to sham who received subsequent crossover ultrasound renal denervation, that procedure led to durable and clinically meaningful reductions in daytime ambulatory blood pressure without any increase in medication burden. Although patients remained on ad-lib, open-label background medications throughout this analysis, and adherence wasn't measured, that does mimic a real-world scenario, and importantly, if perhaps most importantly, consistent with the rest of the research that we've done with this device, the procedure does appear to be safe and very well tolerated.

Thank you.