Split Decision on Renal Denervation for Resistant Hypertension

Patrice Wendling

September 27, 2018

SAN DIEGO — A randomized head-to-head comparison of three different renal denervation approaches appears to give the edge to ultrasound ablation of the main renal arteries in patients with resistant hypertension.

The reduction in daytime ambulatory systolic blood pressure (BP) at 3 months was 13.2 mm Hg with ultrasound ablation, 8.3 mm Hg with radiofrequency (RF) ablation of the main renal arteries and branches, and 6.5 mm Hg with RF ablation of the main renal arteries.

Only the difference between the ultrasound and RF main artery groups reached statistically significance (P = .042).

Daytime diastolic BP reductions followed a similar pattern but were less pronounced, at –7.6 mm Hg, –6.1 mm Hg, and –3.2 mm Hg, respectively.

All three approaches — ultrasound ablation using the Paradise catheter (ReCor Medical) and both RF ablations using the Symplicity Spyral catheter (Medtronic) — had a favorable safety profile in the RADIOSOUND-HTN study, said principal investigator Philipp Lurz, MD, PhD, Heart Center Leipzig at University of Leipzig, Germany.

"The results are encouraging but it is too early to prefer one technology over the other," Lurz said in an interview.

That said, he continued, "It seems when you have very complex anatomy, the spiral catheter might be the easier one to use because it is low profile and it is less stiff. So if you talk about the morphological suitability, this might be a little bit higher with the spiral catheter."

The results were reported here at Transcatheter Cardiovascular Therapeutics (TCT) 2018, and published online in Circulation.

Following the RADIOSOUND-HTN presentation in the main arena and in a press conference, moderator Felix Mahfoud, MD, Saarland University Medical Center, Homburg, Germany, declared that renal denervation is "back on track."

The field took a broadside hit 4 years ago in SYMPLICITY HTN-3, but has gained support in the SPYRAL HTN-ON MED, SPYRAL HTN-OFF MED, and RADIANCE-HTN SOLO trials.

The REDUCE HTN-REINFORCE trial, however, also reported here at TCT 2018, was stopped early for futility with just 51 patients enrolled, and results showed no significant difference between renal denervation using the Vessix catheter (Boston Scientific) and a sham procedure for the primary end point of ambulatory BP at 8 weeks.

At 6 months, however, 52% of those actively treated achieved an office BP below 140 mm Hg, compared with just 12% in the sham group, and mean office systolic and diastolic blood pressures were 11.4 mm Hg and 5.4 mm Hg lower, respectively, in the denervation group (P = .037).

Study author Michael A. Weber, MD, State University of New York, Downstate Medical Center, Brooklyn, New York, said it is not surprising that findings were stronger at 6 months than at 8 weeks, because this was also shown in SPYRAL HTN-ON MED.

"The nerves we ablate are complex, with varying activities, and it takes considerable time for a new equilibrium to be established," he told theheart.org | Medscape Cardiology. "It is also possible that denervation is most effective when combined with antihypertensive drugs. So at 6 months — when most patients in the active and sham groups were receiving medications — we saw a clearly enhanced effect."

"The takeaway from the data," Weber said, "is that the Vessix catheter appears to have similar efficacy to that reported with other devices, although our small patient numbers require caution in reaching conclusions."

SYMPLICITY HTN-3 coprincipal investigator Deepak L. Bhatt, MD, Brigham and Women's Hospital, Boston, told theheart.org | Medscape Cardiology that what needs to happen with any of these devices is a large sham-controlled trial with a diversity of operators to see if the results are reproducible. "Actual, real-world use" of the technology, which is investigational in the United States, is "premature," he said.

"We need trials of several hundred patients to really nail down exactly which patients benefit, how large the effect is, how quickly it kicks in, how durable it is, and what side effects there might be," he added.

In SYMPLICITY HTN-3, "the procedure was extremely safe but that needs to be re-examined now that we're going into branches and accessory arteries."

Paradoxically, trials in this space are notoriously difficult to perform, Bhatt observed, as apparent resistant hypertension often "melts away" once patients are enrolled at a well-run hypertension clinic and nonadherence to antihypertensive drugs is common.

Indeed, 1140 of the 1884 patients screened for RADIOSOUND-HTN were excluded because they had normotensive ambulatory BP, another 35 patients were excluded because they were considered medication nonadherent, and in 555 cases, the patient or general practitioner denied enrollment.

In the end, 120 patients with a daytime ambulatory systolic BP of at least 135 mm Hg — despite treatment with at least three drug classes at 50% or higher maximum dosage, including at least one diuretic — were evenly randomized to the three groups.

The baseline 24-hour average ambulatory systolic BP was 147.4 mm Hg in the RF main-only group, 150.6 mm Hg in the RF main plus branches group, and 151.3 mm Hg in the ultrasound group. Mean diastolic BPs were 83.6 mm Hg, 83.5 mm Hg, and 83.6 mm Hg, respectively. Roughly half the patients in each group had isolated systolic hypertension.

Interestingly, the reductions in daytime ambulatory systolic BP observed with ultrasound ablation did not translate into higher individual patient responder rates at 3 months, Lurz said. The percentage of patients achieving a decrease of at least 5 mm Hg was 66% in the RF main artery group, 73% in the RF main artery plus branches group, and 67% in the ultrasound group.

As to safety, there was one death 2 months after the procedure in the RF main-only group that was unrelated to treatment; one vascular complication in each group; and one hospitalization for hypertensive crisis in the RF main plus branches group. Importantly, there was no evidence of new renal artery stenosis greater than 70% in any group, he said.

Limitations of the study, Lurz said, were the relatively small sample size, the number of ablations in the main and branch artery group, which was lower than in either SPYRAL study, and the fact that no drug testing was used to determine drug adherence.

The trial also included patients with isolated systolic hypertension and those with larger renal arteries, the latter based on the assumption that sympathetic fibers are a greater distance from the lumen than in smaller arteries and, therefore, renal branch artery ablation and higher penetration depth are more relevant.

Commenting on the RADIOSOUND-HTN results, Renu Virmani, MD, CVPath Institute, Gaithersburg, Maryland, told theheart.org | Medscape Cardiology, "The intravascular ultrasound is the better way to go but it just needs numbers to show the differences. It just makes sense."

With RF spiral catheter ablation, "you're doing it in four quadrants. You don't know what the width of your effect is, so you're not really covering all the circumference, likely," she said. "That would be the easiest explanation, but there could be others that we don't understand."

As to the renal denervation field overall, Virmani said, "this is not going to be the be-all and end-all as was originally thought," but for "high-risk patients, patients who don't respond to all the drugs, I would try this treatment."

"Would I want this on myself?" She asked. "No. I am hypertensive; I know I can be controlled on meds. I will take my meds. It's the people who don't take their meds, they're the ones who are going to say, 'Let me go through this, I don't want to take a med.' It will be self-selection once it's approved."

Lurz reported grant support/research contracts with ReCor and Occlutech; consultant fee/honoraria/speaker's bureau relationships with ReCor, Abbott Vascular, and Rox Medical; and the off-label use of MitraClip in the tricuspid valve. Bhatt reports grant support/research contracts with Abbott Vascular, Astra-Zeneca, Bristol-Myers Squibb, Daiichi-Sankyo/Eli Lilly, Medtronic, Sanofi-Aventis, The Medicines Company, and Chiesi.

Transcatheter Cardiovascular Therapeutics (TCT) 2018. Presented September 25, 2018.

Circulation. Published online September 25, 2018. Abstract.

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