May 17, 2011 (Paris, France) — Interventional cardiologists gathered here at EuroPCR 2011 are mulling the potential new applications for renal denervation--the centerpiece of the "live case" presentation that kicked off this year's meeting--even as they admit that the very limited data supporting the procedure in resistant hypertension need to be replicated in larger studies.

The speculation on future uses comes as longer-term data from the Symplicity HTN-1 pilot study are published in the May 2011 issue of Hypertension [1].

"We have relatively limited numbers of patients who have been included in the trials, yet the potential size of the population who could benefit is huge," session chair Dr William Wijns (Cardiovascular Center Aalst, Belgium) observed. "Should this mismatch be addressed by larger trials?"

In a morning press conference, Wijns pointed out that renal sympathetic-nerve denervation was awarded the EuroPCR innovation award in 2010 and that the program committee chose to spotlight the therapy in the opening session of the 2011 meeting to emphasize both the potential and pitfalls of the fledgling approach. "We will look at this with a critical eye, but also considering the impact it may have," he said.

Early and Longer-Term Data

As previously reported by heartwire , the randomized Symplicity HTN-2 study results were first released at the American Heart Association 2010 Scientific Sessions and published simultaneously in the Lancet [2]. The interventional procedure entails bilateral ablation of the renal sympathetic nerves lying adjacent to the renal artery, which play a critical role in the initiation and maintenance of systemic hypertension.

Six-month results in Symplicity HTN-2 suggested that average office-based blood pressure was reduced by 32/12 mm Hg (from a baseline average of 178/97 mm Hg) in patients treated with renal denervation, compared with no measureable change in the control group.

And published this month, new follow-up data from Symplicity HTN-1, a nonrandomized pilot study in 153 patients, suggest that improvements in BP among treated patients are sustained over time: an average reduction of 25/11 mm Hg in this study at six months was almost identical at 12 months (23/11 mm Hg) and increased to 32/14 mm Hg by two years--at least among the 18 patients who had reached two-year follow-up. No late adverse events were seen, the authors note, including no new renal stenosis or aneurysm.

In the live case today, Dr Horst Sievert (Cardiovascular Center, Frankfurt, Germany), performing the ablation procedure live from Frankfurt, wrapped up the case by stenting the renal artery, something that he explained at the outset was his intention, having performed balloon angioplasty in this artery several weeks previously.

More Data, New Settings?

In a presentation reviewing the current evidence and future applications for renal denervation, Dr Robert Whitbourn (St Vincent's Hospital, Fitzroy, Australia) noted that more information on both efficacy and safety should come from the Symplicity HTN-3 study, currently poised to launch in the US. The trial has been designed to randomize 280 patients with resistant hypertension to the denervation procedure and 280 to a control group.

Next, says Whitbourn, is the question of whether renal denervation might also have a role in other arenas. "Are we going too far if we move into early hypertension or borderline hypertension? The question that is often asked is, is this a treatment we can use instead of drugs? And we don't really know the answer to that."

There are also mechanistic studies suggesting that ablating the renal nerves might benefit other diseases, beyond primary hypertension. These include congestive heart failure, which has been associated with a very high sympathetic stimulation rate, Whitbourn noted; a small Australian study is addressing the role of renal denervation in these patients. Patients with chronic renal disease or even renal transplant may also be appropriate candidates. "This is an indication that we will expand over time, Whitbourn suggested, "although there are no real data, no studies in this area at this time."

One Step at a Time

Discussing future options, Dr Charanjit Rihal (Mayo Clinic, Rochester, MN) suggested than any notion of expanding the treatment to less severe hypertension should take into account "how strongly we believe the current evidence." Of note, he pointed out, the Symplicity-HTN 2 trial, while randomized, contained no sham procedure.

"The initial studies are quite strongly positive and the question is whether on the basis of a few hundred patients, we should start on a procedure that would be applied to 20% of the population," Rihal warned.

Dr Thomas Lüscher (University Zurich, Switzerland) also urged caution. "Of course, hypertensive specialists traditionally prescribe drugs and are not performing interventions, so there is a sort of skepticism [over this procedure], and they are also used to much larger trials. . . . I think we should certainly stick to the indication right now and provide some additional data."

Both Lüscher and Whitbourn pointed to the fact that the most suitable patients for this procedure may not actually be the oldest, sickest patients, in whom anatomic changes to the vessels may make them less amenable to renal-nerve ablation.

"Personally," said Lüscher, "I would think that [since] the sympathetic activity is actually highest in the youngest patients with hypertension, they would at least conceptually be more suitable for such an intervention than elderly patients."

Dr Patrick Serruys (Erasmus University Medical Center, Rotterdam, the Netherlands), who also participated in the panel discussion, pointed out that in addition to larger trials, it will be important to see outcomes data, showing that renal denervation actually leads to improvement in hard cardiovascular end points.

The Symplicity HTN studies were supported by Ardian. Lüscher, Rihal, Whitbourn, Serruys, and Wijns disclosed having no conflicts. Sievert disclosed being a consultant for and receiving honoraria and grants/research support from Access Closure, AGA, Angiomed, Ardian, and Arstasis, as well as being a stockholder in Cardiokinetix, Access Closure, and Lumen Biomedical.


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