Shelley Wood

May 24, 2013

PARIS, France — Twelve-month results from the EnlighHTN-1 trial testing the EnlighHTN multielectrode renal-denervation catheter (St Jude Medical) show continued safety and durable efficacy of the BP-lowering effects in this small, first-in-human study.

Dr Stephen Grant Worthley (Royal Adelaide Hospital, Australia) presented the 12-month update here at EuroPCR 2013 amid a riot of studies examining new devices and live cases, one of which skirted disaster.

As previously reported by heartwire , the EnligHTN catheter is a four-electrode radiofrequency-ablation catheter designed to disrupt the renal sympathetic efferent and afferent nerves that contribute to systemic hypertension. The trial originally enrolled 62 patients, 15 of whom were deemed ineligible at the time of screening, and one additional patient was excluded prior to denervation due to renal-artery anatomy.

All of the 46 patients treated with renal denervation were available for one-year follow-up. Eighty percent of treated patients had responded to the therapy (response defined as a 10-mm-Hg or more drop in systolic BP). The average systolic blood-pressure reduction at 12 months was 27 mm Hg, almost unchanged from the drop seen at 30 days and six months. No new safety events were seen between six and 12 months.

Renal Safety Data "Exciting"

Discussing the findings with heartwire , Worthley stressed new data on renal function. Estimated glomerular filtration rate (eGFR) and serum creatinine showed no meaningful changes between six months and one year, while cystatin C actually declined from 1 mg/L at six months (1.14 mg/L at baseline) to 0.91 mg/L. Likewise, the urine albumin-to-creatinine ratio declined significantly from baseline to 12 months. Both of these, Worthley explained, are more accurate, independent markers of renal function than serum creatinine. While the early kidney-function data are reassuring in that they indicate that there are no adverse renal effects related to the procedure itself, these later data offer a hint that the blood-pressure decline may be having some positive effects on the kidney itself, something Worthley called an "exciting" prospect.

One thing the EnligHTN-1 investigators are not seeing is a delayed benefit--something much discussed in the Symplicity HTN-1 trial data. Worthley attributes this to the more consistent pattern of transmural lesions delivered by the multielectrode device. Other devices, including the Covidien One-Shot device, also denervate via a multielectrode approach, while the latest iteration of the Symplicity renal-denervation catheter, the Spyral, also boasts a multielectrode design.

Multielectrode designs also have the advantage of reducing procedure times, which is less painful for patients.

Speaking with heartwire , Worthley said that while some patients have had their hypertension class downgraded as a result of their denervation treatment, the average number of hypertension medications they are taking has not, on average, declined. While some have dropped a drug, others have started a new one, he said. "And that speaks to the point that this is an adjunctive to medication, not a replacement," he said.

Innovation and Caution

The EuroPCR 2013 program is plump with "abstract," "tools-and-techniques," and "innovation" sessions dedicated to new and up-and-coming renal-denervation systems. Many are moving forward with tried-and-true radiofrequency ablation systems, while others are exploring ultrasound, microwave, ethanol, and even Botox approaches.

Asked where he thought the field was headed, Worthley said: "We have years of safety data with radiofrequency energy, so before we see any of those other techniques used in significant numbers of patients, we're going to need to be comfortable with the safety data."

And even more important than the devices themselves, he added, is answering the clinical questions. "Who are the responders? How do we identify them? One in five patients don't respond, and that's pretty constant across studies. Why don't they respond? The higher the heart rate, the bigger the reduction, but we don't fully understand why this is."

As well, physicians need to be very careful in managing expectations with patients: 20% will not respond, for unknown reasons, Worthley reiterated. And even patients who "respond," according to the definition of 10 mm Hg or more, may be disappointed with an outcome in the range of a 10- or 12-mm-Hg drop, he warned.

Also lacking are any outcomes data. Earlier this week, Dr Felix Mahfoud (Saarland University, Saar, Germany) outlined plans for St Jude's recently launched EnligHTNment trial, with a planned 4000 patients, powered to show a 25% reduction in major adverse cardiovascular events. The trial will randomize patients with systolic blood pressures of >160 mm Hg, uncontrolled on two or more drugs, and with three additional risk factors for CVD.

Open Questions, Concerns

Asked if he had any niggling concerns about renal denervation, which is clearly being giddily embraced by physicians and industry alike, Worthley had two. One is the very rare cases of accelerated renal-artery stenosis seen after the denervation procedure--at least one case has been seen in trials of both St Jude and Medtronic's devices, Worthley said.

"It seems thermal injury may accelerate or provoke stenosis in some patients," he said. Patients with 30% stenosis or greater are typically excluded from denervation trials because of this risk.

Worthley's second concern relates to streamlining the procedure and minimizing risks. "There was a live case here at EuroPCR where they actually dissected both renal arteries," he told heartwire. The dissections were stented "and the patient has done well, which is pleasing, but exploring potential options that allow us to reduce that low-frequency risk will be important for the future," he said.

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