ISET Panel Considers Future of Renal Denervation to Treat Hypertension

February 2, 2015—A panel at ISET 2015: the International Symposium on Endovascular Therapy in Hollywood, Florida, discussed the past and future investigations of renal denervation (RDN) as therapy for treatment-resistant hypertension (HTN).

As reported in the conference’s daily newspaper, ISET Today, leading panelist Martin Leon, MD, noted that the SYMPLICITY HTN-2 study results encouraged growth of the use of the treatment until the announcement of the SYMPLICITY HTN-3 failure in early 2014.

Regarding RDN, Dr. Leon asked, “What’s the next step? How do we move forward if we believe this has any future in treating our patients with hypertension?” He continued, “It is a safe therapy. Since there is confidence in RDN safety, we can transition to new studies with earlier-stage hypertension patients. We need to treat RDN like any new hypertension therapy.”

Dr. Leon advised that a clinical trial now in development could hold promise for RDN. Boston Scientific Corporation has received US Food and Drug Administration approval for the REDUCE-HTN: REINFORCE clinical trial for the company’s Vessix RDN system. He stated, “The trial should begin in approximately 1 to 3 months. It will get us back on the right direction. We’ve lost a lot of momentum. We’ve learned it’s going to be a little more convoluted to get back on the path to use RDN to treat hypertension.” He also noted that Medtronic is developing a new clinical trial to further investigate RDN, reported ISET Today.

In October 2013, the 3-year results from Medtronic’s SYMPLICITY HTN-2 results were presented at the TCT 2013: Transcatheter Cardiovascular Therapeutics conference in San Francisco, California. The data were subsequently published online in the European Heart Journal.

In January 2014, Medtronic announced that its SYMPLICITY HTN-3 trial failed to meet its primary efficacy endpoint. The SYMPLICITY HTN-3 data were presented in March at ACC.14: the 63rd annual scientific sessions of the American College of Cardiology in Washington, DC, and concurrently published by David E. Kandzari, MD, et al in the New England Journal of Medicine (2014; 370:1393-1401). At ACC.14, Medtronic announced that it would commit to further investigation of the treatment.

ISET Today reported that Dr. Leon outlined three factors contributing to the HTN-3 trial’s failure to demonstrate efficacy: (1) operator experience was low, with a median of 2.6 cases per operator; (2) identifying patients with resistant hypertension is difficult; (3) the demographics of patient selection.

Dr. Leon proposed two possible clinical trial designs. One would be a proof-of-concept study of treatment of patients with early stage I/II HTN to wean them off medications. The study would evaluate placebo versus RDN with an early 1-year endpoint determination. The other study would be an assessment of therapeutic effect of RDN in patients with poorly controlled HTN. The study would compare a fixed multidrug regimen (perhaps using a standard polypill) versus RDN in addition to the fixed drug prescription.

ISET panelist Ron Waksman, MD, cited the complexity of the HTN-3 trial as a reason for its failure and also remarked on the good news of the safety of RDN demonstrated in the trial. Dr. Waksman outlined the following conditions for the potential success of RDN: identify the right target population; identify the target nerve for ablation; improve catheter design; receive immediate feedback on the ablation’s effectiveness; and create the appropriate trial design. He added, “We do know that if you ablate more, you will get a blood pressure reduction. But how much do you need to ablate? And where do you ablate?”

Michael Jaff, DO, suggested that potential new applications for RDN other than hypertension treatment include chronic kidney disease, diabetes and metabolic syndrome, atrial fibrillation, and obstructive sleep apnea.

Panelist Melvin Lobo, MD, noted that the failure of SYMPLICITY HTN-3 resulted in a reduction of RDN treatment throughout Europe, particularly in Germany, because insurance companies are reluctant to reimburse for the therapy. He noted that the French DENER-HTN trial of RDN with Medtronic’s Symplicity catheter has set the bar for future hypertension studies. “I do believe RDN has a future. But we need better markers of efficacy,” commented Dr. Lobo, according to ISET Today.