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PARIS -- Radiofrequency- and ultrasound-based renal denervation showed modest blood pressure reductions in two sham-controlled studies reported here.

In SPYRAL HTN-ON MED, ambulatory blood pressure dropped by 9.0/6.0 mm Hg with renal denervation by the Symplicity Spyral catheter versus 1.6/1.9 mm Hg with a sham procedure.

In the RADIANCE-HTN SOLO trial, the Paradise ultrasound renal denervation ablation catheter cut daytime ambulatory blood pressure by 8.5 mm Hg at 2 months, compared to 2.2 mm Hg with sham (P<0.001).

The trials were reported here at the EuroPCR meeting and simultaneously online in .

"Both trials were well designed and executed. Both studies were remarkably consistent in their findings – a significant, albeit modest-sized, reduction in ambulatory and office blood pressures," commented Deepak Bhatt, MD, MPH, of the Brigham and Women's Hospital in Boston, who was not involved in either trial.

Even these modest drops in blood pressure are "clinically worthwhile" and "would be expected to translate into a meaningful reduction in cardiovascular events if sustained over time, assuming there were no counterbalancing side effects," Bhatt told MedPage Today.

That's not to say that the technologies are ready to be approved in the U.S., he said.

"We need to make sure the procedure is durable and that re-innervation doesn't substantially diminish these already modest results. I also think we need to tweak the technology and try to get better blood pressure reduction (while hopefully not compromising procedural or long-term safety)," according to Bhatt.

SPYRAL HTN-ON MED

Renal denervation with the Symplicity Spyral Catheter was studied in a population that stayed on a stable regimen of one to three antihypertensive medications for at least 6 weeks (averaging just over two antihypertensive drugs). Those who were randomized to denervation had "statistically significant and clinically relevant" blood pressure reductions over 6 months compared with those who got a sham procedure instead:

• Ambulatory systolic blood pressure: 9.0-mm Hg drop versus 1.6 mm Hg with sham at 6 months (P=0.005)
• Ambulatory diastolic blood pressure: 6.0-mm Hg reduction versus 1.9 mm Hg (P=0.03)
• Office systolic pressure: 9.4-mm Hg decrease versus 2.6 mm Hg (P=0.02)
• Office diastolic pressure: 5.2-mm Hg reduction versus 1.7 mm Hg (P=0.048)

A steady drop in ambulatory blood pressure and zero safety events were observed over this period, David Kandzari, MD, of the Piedmont Heart Institute in Atlanta, told the audience at the late-breaking trial session.

Kandzari's group had shown last year in the sham-controlled SPYRAL HTN-OFF MED trial that renal denervation with the Symplicity Spyral catheter could lower blood pressure modestly in the absence of antihypertensive medications.

SPYRAL HTN-ON MED was conducted at 25 sites across Germany, the U.K., Austria, Greece, Japan, Australia, and the U.S. Investigators screened 467 patients to get 80 patients randomized to sham or actual denervation. Denervation was done with the novel Symplicity Spyral device, a multi-electrode catheter (allowing simultaneous ablation in up to four electrodes) that is also flexible enough to treat branches.

Patients in the denervation and sham arms went into the trial with mean office systolic blood pressures of 164.6 mm Hg and 163.5 mm Hg, respectively; baseline 24-hour systolic blood pressures averaged 152.1 and 151.3 mm Hg.

Separately, renal denervation based on endovascular ultrasound was also found to work, according to another sham-controlled study -- only this time in patients who were hypertensive after a 4-week blood pressure medication washout.

RADIANCE-HTN SOLO

In this trial, the Paradise ultrasound renal denervation ablation catheter reduced blood pressure with no safety events at the 1-month mark.

Advantages to the denervation procedure reported by Laura Mauri, MD, MSc, of Brigham and Women's Hospital, at the EuroPCR session included:

• Patients achieving at least a 5-mm Hg decrease in daytime ambulatory systolic blood pressure: 66% versus 33% for sham (P<0.001)
• Daytime ambulatory blood pressure under 135/85 mm Hg achieved: 20% versus 3% (P=0.001)
• 24-hour ambulatory blood pressure under 130/80 mm Hg achieved: 24% versus 3% (P<0.001)

"Endovascular ultrasound-based renal denervation effectively lowered blood pressure in patients with mild to moderate hypertension who were randomized and followed for 2 months off medications," according to Mauri. "Follow-up is ongoing through 3 years to assess longer term safety and efficacy."

The 2-month results of RADIANCE-HTN SOLO were also published online in .

Trial investigators at 39 centers in the U.S. and Europe screened 803 patients in order to get 146 that were eligible for randomization. Ultrasound denervation required an average of more than five ablations delivered to each main renal artery.

Next Steps

Referring physicians and third-party payers should demand more sham-controlled randomized data and longer-term data regarding both blood pressure efficacy and procedural safety of renal denervation, Bhatt urged, adding that findings from the Symplicity Spyral and Paradise programs need to be validated in appropriately-powered multicenter trials of many more patients.

To that end, the SPYRAL HTN Pivotal trial is underway in an off-medication population totaling up to 433 patients.

Additionally, Mauri noted that the sham-controlled RADIANCE-HTN TRIO trial of renal denervation with the Paradise catheter in patients with resistant hypertension, is currently in the enrollment phase.

"The million dollar question is whether third party payers would embrace an expensive, minimally invasive procedure with a single digit reduction in blood pressure," Bhatt said.

"I don't see third party payers being that excited about an expensive therapy with modest effect, when so many generic drugs are available for hypertension. We learned in SYMPLICTY HTN-3 that most 'resistant' hypertension is really non-adherence. And that is a big problem in real life, for sure, but I believe third party payers will want robust cost-effectiveness data prior to reimbursing for renal denervation," he predicted.