Renal Denervation Shows Durable Blood Pressure Benefits in Key Trials: Deepak L. Bhatt, MD, MPH, MBA

In part 3 of an interview at the ASPC 2025 Congress on CVD Prevention, Deepak L. Bhatt, MD, MPH, MBA, of Mount Sinai Fuster Heart Hospital, summarizes findings from the SPYRAL HTN-ON MED (NCT02439775), SPYRAL PIVOTAL/HTN-OFF MED (NCT02439749), and RADIANCE-HTN (NCT02649426) trials. He highlights that renal denervation showed consistent but modest blood pressure reductions in sham-controlled phases, with longer follow-up suggesting more durable benefits.

Revisit parts 1 and 2 of the interview to learn more about how renal denervation works, along with its potential benefits and risks.

This transcript has been lightly edited; captions are auto-generated.

Transcript

Renal denervation is often considered in patients who have resistant or uncontrolled hypertension, but interest is growing in low-to-moderate-risk patients who want to reduce or avoid medications. Key trials include SPYRAL HTN-ON MED, SPYRAL PIVOTAL/HTN-OFF MED, and RADIANCE-HTN. Can you discuss how these trials evaluated the therapy and their findings?

Within the series of trials, most have involved the radiofrequency catheter made by Medtronic—there have been a few generations of that—or the Paradise Ultrasound System by Recor [Medical]. Those are the 2 [main] companies. There are other companies, as well, that have developed and are developing catheters and various approaches. I alluded to, for example, alcohol injection via balloons and even other things. Several companies in China, for example, have catheter systems that seem to have pretty good data, as well.

In terms of the 2 major programs, it's the Simplicity Spyral program that's evaluated the Medtronic catheter and the RADIANCE program that's done the Paradise catheter by Recor. I would say the totality of evidence of both those programs, especially if you do meta-analyses and that sort of thing, shows significant, albeit modest, reductions in blood pressure during the rigorous randomized, sham-controlled phases of the trial. Then, with longer follow-up in the unblinded, nonrandomized portion of the follow-up of those trials, there seems to be a durable benefit, no late-emerging [adverse] effects. If anything, [there were] increasing degrees of benefit with respect to blood pressure control.

None of the trials were powered to look at heart failure, kidney failure, ischemic events, that sort of thing, so we'll talk about blood pressure control. If anything, there is a reduction in the burden of medications, antihypertensive medications, despite the fact that there's better blood pressure control in those patients initially randomized to the renal denervation procedure.

It does seem that for both of these FDA-approved catheters, there is a significant benefit in terms of lowering blood pressure, modest in the very rigorous randomized control environment but much larger during the longer-term observational phase of these trials. It does look like there's at least a modest benefit and maybe a larger benefit in real-world practice, where patients really aren't taking 5, 6, or 7 medicines a day, multiple times a day; that rarely actually happens outside of the somewhat artificial context of clinical trials.

I think we did the right thing in the clinical trial domain with renal denervation. SIMPLICITY HTN-3 (NCT01418261), which the late George Bakris, MD, and I led, sort of reset the field and the expectation that rigorous trials be done with sham controls, blinding, and so forth. I think that was necessary to prove that there really was something there in terms of blood pressure reduction, but now that that's been established, at least with these 2 catheters and really others, as well, I think we can move beyond the stage of saying, "Does it work?" and try to identify which patients benefit the most and how we can use this therapy in a cost-effective way.

In terms of one of the points you raise about patients that were lower-risk, and by that, I assume you mean lower blood pressure, instead of going on medicines, I think it's probably best to maximize lifestyle modification and generically available common, familiar medicines before going on to any type of invasive procedure, even one with relatively low risks. Beyond my own opinion, I think that third-party payers, insurers, likely aren't going to be super excited about substituting a procedure for a generic medication. At least in the rigorous randomized phases of these trials, the blood pressure reductions are modest, on the order of 5 or 6 mm Hg in many cases, so a generic drug can accomplish that, as well.

On the flip side, with renal denervation, one of the things that's been touted is the "always on" phenomenon. That is, you don't have to worry about adherence because it's a procedure. Once it's done, hopefully successfully, that effect lasts, at least as far as we can tell, 24 hours a day for a minimum of 5 years. That's what we saw, for example, in the long-term follow-up of SIMPLICITY HTN-3, and perhaps even longer. We have to see whether patients will need reapplication of the therapy, but it does seem to be durable, at least up to that time frame of 5 years or so, based on randomized clinical trial data, albeit the observational phases of trials, such as SIMPLICITY HTN-3.

If it is a therapy that could just be administered once in a lifetime, that would affect its cost-effectiveness favorably and get around things like patient adherence to multiple pills multiple times a day. On the other hand, if it turns out that it's not durable after 10 years or longer follow-up, then one might need to consider, again, in terms of cost-effectiveness, exactly where it fits in. Again, it'll have a role; it's just a matter of determining at what price it truly is cost-effective.