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|Bigger BP Drop Goal for Renal Denervation - MedPage Today|
By Crystal Phend, Senior Staff Writer, MedPage Today
Published: May 18, 2012
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.
PARIS -- More dramatic blood pressure reductions may be on the horizon for patients with resistant hypertension given the phalanx of renal denervation systems under development.
Results of pilot studies on a variety of novel renal sympathetic nerve ablation catheters are achieving in the range of 28/10 to 32/15 mm Hg blood pressure reductions at one month, researchers reported here at the EuroPCR meeting.
Clinical trials of the first such device -- the Symplicity single-electrode radiofrequency ablation device, on the market in Europe -- showed a 1-month drop in BP of 14/10 to 20/7 mm Hg in clinical trials.
"New second generation devices may be improving not only safety but also efficacy," Stephen Worthley, MBBS, PhD, of the University of Adelaide, Australia, told MedPage Today.
Although still in the early phases of clinical study, stenosis or other complications to the renal artery haven't been a problem across the systems, he and several other groups reported at sessions on the percutaneous renal denervation device pipeline.
"We do see local effects but they don't seem enduring," said one session chair Robert Whitbourn, MBBS, of St. Vincent's Hospital in Melbourne, Australia. "RF seems to be very clean energy. The artery does seem robust."
Nerves are more sensitive than arteries to damage from high temperatures, explained another moderator, Ron Waksman, MD, of Washington Hospital Center in Washington, D.C.
Arteries, too, vary in their tolerance, with the renal artery apparently able to handle damage better than the pulmonary artery, for example, he added.
Multi- or Large-Electrode Systems
First-in-man trial results with the four-electrode EnligHTN radiofrequency ablation device showed no serious complications related to the device or the procedure, such as renal artery dissection, aneurysm, stenosis, or flow-limiting vasospasm.
The 46 resistant hypertension patients treated did have some minor procedural events, including four cases of hematoma, three vasovagal responses at sheath removal, and two cases of post-procedural transient bradycardia.
Renal function didn't appear affected at one month.
But office-measured blood pressure dropped by an average 28/10 mm Hg from a mean of 176/96 at baseline to 148/87 at 1 month (P<0.0001), Worthley reported.
Altogether, 78% of the patients were considered responders with at least a 10 mm Hg systolic reduction, and 41% got down to the goal of 140 mm Hg.
Another device with eight electrodes on a balloon catheter gave similar results in the first 10 patients reported by Raymond Cohen, CEO of device maker Vessix Vascular, in the REDUCE-HTN study.
No complications were seen, but 1-month blood pressure fell by 30/11 mm Hg, with all patients being responders.
Another design strategy is a spiral electrode around the catheter head to provide multiple ablations at once.
Preclinical results reported with the OneShot system showed effective ablation of renal nerves and an 84% reduction in renal norepinephrine content compared with controls, which would limit the sympathetic activation that raises blood pressure.
But not all the devices are sticking with radiofrequency ablation, generating elevated temperatures with other strategies instead.
The Paradise system, for example, uses an ultrasound catheter to heat circumferentially at a depth while cooling the endothelium of the vessel it is in direct contact with.
In the pilot REDUCE trial with that novel strategy, no serious device-related adverse events occurred among the 15 treated patients, although there was one artery dissection from the catheter sheath.
Office-measured blood pressure fell by an average 30/14 mm Hg at 1 month and was 32/16 below baseline at 3 months, Raoul Bonan, MD, of the Montreal Heart Institute in Canada, reported at the conference.
Two other groups reported on strategies without clinical experience yet:
Cautions for the Field
Despite the promise of renal denervation for treating a difficult condition -- by definition persistent hypertension despite treatment with three or more antihypertensives, including a diuretic -- experts in the field urged a careful path for clinical practice and research alike.
The alteration in the renal artery is irreversible, Jean Renkin, MD, of St. Luc University Hospital in Brussels, Belgium, noted at the conference's "great debate" session.
"One of the main messages will be proper selection of patients for this procedure," he said.
That's key because patients are going to be driving demand for renal denervation, noted nephrologist William McKane, MB, of the Sheffield Kidney Institute in Sheffield, England.
"You're going to have patients knocking on your door asking for this treatment," he told attendees. "It's important to understand what we know but also what we don't know."
Some of those questions are how the treatments compare with sham control, which none of the studies yet have used, and what the long term outcomes will be with the denervation procedure.
Renal nerves can regrow, although data from the Symplicity trials suggest a durable effect over at least 3 years.
Also, the epidemiologic data projecting the effect of a particular blood pressure difference on mortality and other outcomes hasn't panned out quite as well in interventional trials, McKane cautioned.
Another concern is that renal artery stenosis may develop slowly, taking up to a decade to show up after radiation, he added.
The Symplicity trial excluded patients with even moderate or more advanced kidney disease and its quality of surveillance for complications wasn't compelling, McKane argued.
"It's too early to tell what the impact on GFR [glomerular filtration rate] is really going to be," he said.
For the time being, it's important to reserve renal denervation procedures to only good renal teams with representation by hypertension specialists, radiologists, and nephrologists that can carefully screen patients for truly medication-resistant hypertension, Renkin suggested.
"We need to be very careful that we do not kill a promising technology with incorrect patient selection," agreed Pierre-Francois Plouin, MD, of the Hospital Europeen Georges Pompidou in Paris, and a past president of the French Society of Hypertension.
The EnligHTN trial was supported by St. Jude Medical.
Worthley reported having no conflicts of interest to disclose.
The REDUCE-HTN trial was supported by Vessix Vascular.
Cohen reported being CEO of Vessix Vascular.
The Paradise renal denervation device study was supported by ReCor Medical.
Bonan reported consulting and being a stockholder in ReCor Medical.
Whitbourn reported research support from Abbott Vascular, Boston Scientific, and Medtronic.
Waksman and Plouin reported having no conflicts of interest to disclose.
Renkin and McKane reported receiving honoraria from Medtronic.
Primary source:EuroPCR meeting
Additional source: EuroPCR meeting
Additional source: EuroPCR meeting
Crystal Phend joined MedPage Today in 2006 after roaming conference halls for publications including The Medical Post, Oncology Times, Doctor’s Guide, and the journal IDrugs. When not covering medical meetings, she writes from Silicon Valley, just south of the San Francisco fog.