Experts Debate Future of Renal Denervation

Use of renal denervation to treat resistant hypertension remains controversial. In a debate held at TCT 2014, two experts in the field discussed the weight of evidence for renal denervation and its possible staying power.

Subgroups matter but perhaps not operator experience 

Deepak L. Bhatt, MD, MPH, of Harvard Medical School in Boston, Mass., said that denervation can only be recommended if sufficiently powered trials using a sham-control group can document benefit. So far, that has not been the case. SYMPLICITY HTN-3, which with 535 patients represents the only major randomized study to date, demonstrated significant (P<.001) — though nearly identical — drops in office systolic BP between baseline and 6 months for the treatment (−14.13 ± 23.93 mm Hg) and control groups (−11.74 ± 25.94 mm Hg; P=.26). “This demonstrates the value of having a sham control,” said Bhatt, a SYMPLICITY HTN-3 investigator. “If it were only the denervation arm, it would have been a positive trial.”

There were some hints of benefit seen in subgroups, including younger patients, non-African Americans, and those with higher estimated glomerular filtration rates. Bhatt noted, however, that these still did not reach significance and contradicted a priori predictions. He also said that the similar results between patients initially randomized to denervation and those who crossed over to treatment call into question the idea that operator learning curve will help improve results. “There’s been a lot made of that, but frankly I’m very skeptical,” he commented.

But Felix Mahfoud, MD, of Saarland University Hospital, Homburg, Germany, pointed out that there is a fairly large body of evidence that renal denervation does in fact lower BP. The global SYMPLICITY registry, he pointed out, represents one of the largest cohorts, and operators were relatively experienced (59% performed more than 15 procedures). Renal denervation decreased office systolic BP by 11.6 ± 24.7 mm Hg at 6 months in 784 patients and by 13 ± 26.3 mm Hg at 12 months in 740 patients. Specifically, in 252 more labile patients (baseline office systolic BP ≥160 mm Hg, mean 24-hour systolic BP ≥135 mm Hg, and more than three antihypertensive drug classes prescribed), the 6- and 12-month reductions were 19.3 ± 22.4 mm Hg and 21.5 ± 25.6 mm Hg, respectively (P<.0001 for all vs. baseline). Additionally, in the French DENER-HTN study, a primary efficacy endpoint of improvement in daytime ambulatory 24-hour BP was met, with a 5.9 mm Hg greater reduction in BP for denervation patients compared with controls group at 6 months (P=.03). Nighttime BP was also improved with denervation.

New devices, optimization of procedures could improve outcome 

Mahfoud noted that in SYMPLICITY HTN-3, first-generation denervation devices were used. Newer versions allowing circumferential ablation and equipped with other features may yet prove more beneficial. There also appears to be some correlation between the number of ablations and the change in office systolic BP, suggesting procedural details should be reexamined, he added. In contrast with Bhatt, Mahfoud said he believes that more experienced operators might influence results, as more than half of the clinicians in the SYMPLICITY HTN-3 trial had performed two or fewer procedures.

Bhatt did agree that newer devices could yield benefit, and that patients who cannot be treated as aggressively with antihypertensive medication could fare better than those included in the SYMPLICITY HTN-3 trial.

Those types of questions suggest a continued role for research into this area, Mahfoud argued. “I do believe that we should continue investigating [renal denervation] as a therapeutic approach not only to treat hypertension but [also] indeed to interfere with the sympathetic nervous system in several disease states,” he concluded.

Disclosures:  

• Bhatt reports relationships with multiple pharmaceutical and device companies.

• Mahfoud reports relationships with multiple pharmaceutical and device companies.