麻豆传媒

A first-in-man study suggested that chemical denervation of the renal arteries might be a safe way to reduce refractory hypertension.

There were no complications related to renal denervation by infusion of ethanol into the adventitial and periadventitial spaces of the renal artery -- creating an ablation zone of injured nerve fibers -- when limited to a dose of 0.3 mL alcohol per artery.

At 6 months following the procedure, mean systolic blood pressure had fallen from 172 mm Hg to 149 mm Hg, while diastolic pressure dropped from 96 mm Hg to 84 mm Hg, , of Michigan State University in Kalamazoo, and colleagues found.

In addition, angiography revealed no renal artery stenosis, aneurysms, or other abnormalities, the group reported online in JACC: Cardiovascular Interventions.

These early data "are encouraging and suggest that chemical denervation with microdoses of alcohol is safe and essentially painless and may effectively reduce blood pressure in patients with resistant hypertension, even in the face of a reduction of antihypertensive medications," Fischell's group concluded.

Ultimately, "renal denervation may prove to be a valuable intervention to treat uncontrolled severe hypertension as well as a number of other conditions that may be driven by sympathetic imbalance or 'overdrive,'" the authors wrote. "The device was very simple to use, with catheter positioning and denervation being performed in as little as 2 to 5 min per artery."

After the disappointments with thermal renal denervation in the SYMPLICITY HTN-3 randomized trial, some blamed the specific radiofrequency system used in the study, operator-related issues, insufficient circumferential ablation, and not being distal enough, , of MedStar Washington Hospital Center in Washington, D.C., noted in an accompanying editorial.

"If these are the main reasons for the failure of the efficacy of SYMPLICITY HTN-3, chemical denervation can resolve these issues as the alcohol can be spread diffusely, circumferentially, deeply, and distally and has the potential to affect more sympathetic nerves via the chemical approach," he suggested.

The potential downside to chemical denervation, however, "is the lack of control and selectivity of the alcohol to the nerves and the risk that alcohol may potentially damage adjacent tissue," Waksman wrote, which is why it is "comforting" to have early data demonstrating its safety.

Still, "it may be naive to believe that ablation of the renal sympathetic nerves alone will be sufficient to control resistant hypertension," he added. "If the failures are not technology related and more driven by disease heterogeneity and variability in response, we should not expect a change in the results when chemical denervation, or any other technology, is tested in a large randomized clinical trial."

SPYRAL HTN-OFF MED and REDUCE-HTN -- "pilot studies using second-generation radiofrequency technology with a novel study design, including moderate hypertension" -- will provide more answers, he noted.

The study by Fischell's group included 18 individuals from Paraguay who underwent treatment with the Peregrine System Infusion Catheter.

Over 6-month follow-up, the treated individuals took fewer hypertension medications (3.4 at baseline versus 2.0 at 6 months). Despite this reduction in medications, systolic blood pressure had declined by a mean of 24 mm Hg and diastolic pressure by 12 mm Hg.

While Fischell and colleagues suggested that a doubled dose of alcohol may be even more effective, they acknowledged that their study had several weaknesses.

Chief among those were the small sample size and the lack of a control group. Furthermore, there were no ambulatory blood pressure monitoring measurements. Patients also showed inconsistent compliance with antihypertensive medication therapy.

Waksman added that there was no independent clinical event committee to adjudicate events and the problem of the principal investigator participating in the adjudication.

"Finally, it is unusual that the American company and investigators selected to perform their investigation in Paraguay. Such early feasibility studies should be conducted in the United States under the early feasibility studies program, which has been initiated by the U.S. FDA," Waksman noted.