Experts Debate Future of Renal Denervation Therapy

 

In a special debate held at TCT 2014, two experts disagreed over whether there is still hope for renal artery denervation after its failure in the SYMPLICITY HTN-3 trial.

sat.kandzari.headRenal denervation was considered a potential breakthrough therapy for treatment-resistant hypertension until Medtronic announced in January that its Symplicity device did not meet the primary efficacy endpoint — change in office systolic BP at 6 months — in the SYMPLICITY HTN-3 trial of 535 patients with severe treatment-resistant hypertension (-14 ± 24 mm Hg for renal denervation vs -12 ± 26 mm Hg for sham procedure; P=.26 for superiority with a margin of 5 mm Hg). Full findings from the trial were presented in March at the American College of Cardiology/i2 Scientific Session and simultaneously published in The New England Journal of Medicine.

A way forward

David E. Kandzari, MD, of Piedmont Heart Institute, Atlanta, said during the discussion that the failure of SYMPLICITY HTN-3 does not necessarily mean that there is no future for renal denervation as a therapy for patients with treatment-resistant hypertension.

“There still is an opportunity … for the study of renal denervation,” he said. “It is certainly by no means dead in the water.”

Kandzari said there was no single reason for renal denervation’s lack of efficacy in SYMPLICITY HTN-3. Concomitant medical therapy could have played a factor, he suggested, as approximately 40% of trial participants required medication changes between baseline and 6 months, and use of some medications was associated with better or worse outcomes for renal denervation.

Another factor may have been that the more ablations performed on a SYMPLICITY HTN-3 patient, the greater the reduction in office systolic BP (P=.01). In addition, those who received four-quadrant ablations on both kidneys had better results compared with those who received them on one kidney or not at all, he said.

Therefore, revisiting physiology and identifying practical measures for effective sympathetic interruption may be worthwhile, Kandzari said. “These are patterns … that are consistent and therefore justify further investigation of renal denervation therapy,” he said.

Future trials for the therapy in patients with treatment-resistant hypertension will need to be designed carefully to demonstrate biological efficacy and differentiate potential confounders of observer and patient bias, Kandzari said. He added that it might be worthwhile to focus on endpoints that are less variable than office BP, such as ambulatory BP.

Time to move on

sat.bangalore.headSripal Bangalore, MD, MHA, of the New York University School of Medicine, said, however, that treatment-resistant hypertension is not a good indication for renal denervation.

One reason is that it is difficult to separate the effects of medications from the effects of the procedure, he said, noting that by the 3-year mark of SYMPLICITY HTN-1 — the first major trial of the Symplicity device — participants were taking an average of 5.6 antihypertensive medications.

Another is that some of the subgroups in whom the procedure was least effective, including elderly patients, African-American patients and those with renal insufficiency, are also those who are at high susceptibility for treatment-resistant hypertension, he said.

The theory that the placebo effect from the sham surgery might wear off in the long term has also been debunked, as 1-year results of SYMPLICITY HTN-3, presented earlier this month at the European Society of Cardiology Congress, continued to show no difference in office systolic BP reduction between the groups, Bangalore said.

“The BP-lowering efficacy of [renal denervation] is highly variable,” he concluded. “Basic questions are not answered, such as how much denervation is optimal and how to standardize the denervation.”

  

Disclosures:

  • Bangalore reports no relevant conflicts of interest.
  • Kandzari reports relationships with multiple pharmaceutical and device companies.

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