CHICAGO — The Symplicity renal denervation system provided reductions in blood pressure that were sustained for up to 3 years in patients with treatment-resistant hypertension, according to data from two clinical trials presented at the American College of Cardiology’s 61st Scientific Sessions.
Paul A. Sobotka, MD, professor of medicine and cardiology at the Ohio State University, presented 3-year results from Symplicity HTN-1, a series of pilot studies that enrolled 153 patients with treatment-resistant hypertension at sites in Australia, Europe and the United States. Eligible patients in this study had systolic BP ≥160 mm Hg despite use of at least three antihypertensive drugs, including a diuretic, at target or maximal tolerated doses. Exclusion criteria included an estimated glomerular filtration rate <45 mL/min/m2 or type 1 diabetes.
One-year results from Symplicity-HTN-1 indicated that patients who crossed over to denervation after previous pharmacologic therapy also achieved sustained reductions in BP.
“A sustained significant BP reduction has been observed through 36 months,” Sobotka said during an oral session. “There is no evidence of reversal or regression of BP advantage bestowed early on.”
Nonresponders were defined, arbitrarily, according to Sobotka, as patients with failure to reduce BP more than 10 mm Hg.
“At 1 month, the responder rate was 0%, but by 36 months, the full cohort responded with reductions of 10 mm Hg.
Sobotka also discussed “late responders,” or patients who had no response at 1 month.
“Of 45 patients who had no clinical response at 1 month, 58% had a 10 mm Hg drop in BP at 3 months, and at 36 months, we are seeing all patients with a clinical response to the initial renal denervation.”
Reductions in diastolic and systolic BP were observed in patients aged older than 65 years or younger than 65 years, according to Sobotka.
“Age does not discriminate the time course, durability or magnitude of the response itself,” he said.
The treatment was also durable in terms of BP behavior regardless of diabetes status, according to Sobotka.
“On the basis of renal function, we bifurcated the group with patients who had estimated glomerular filtation rates between 45 and 60 mL/min/m2, and those who had estimated glomerular filtation rates of greater than 60 mL/min/m2,” Sobotka said. “By 12, 24 and 36 months, there is no significant difference to the systolic and diastolic reductions in BP on the basis of preceding renal status.”
Sobotka also reported no significant changes in renal function at any time interval.
Regarding safety, Sobotka reported one progression of preexisting stenosis unrelated to the current treatment and one moderate stenosis that was not hemodynamically relevant. There were three deaths, none of which were related to the treatment. There were no catheter or generator malfunctions and no major complications.
Murray D. Esler, MD, of the Baker IDI Heart and Diabetes Institute in Melbourne, Australia, reported 1-year results from the international, multicenter, prospective, randomized, controlled Symplicity HTN-2 trial. Fifty-two patients were assigned to renal denervation treatment and 54 patients to a control group that remained on previous therapy. At 6 months, patients in the control group were allowed to cross over to denervation treatment. Esler presented results on 35 crossover patients.
Patients who crossed over at 6 months had a similar significant drop in BP as patients receiving immediate denervation.
“At 12 months post denervation, the reduction in BP was similar to the initially denervated group,” Esler said.
He noted that long-term safety outcomes were “good,” with three hypertensive events reported in two patients in the crossover group. No deaths occurred.
“There may be significant costs associated with delaying denervation,” Esler said. “These patients were treated with 6 months of medication that was essentially ineffective.”
The novel Symplicty renal denervation system (Medtronic) is not currently approved by the FDA for distribution in the United States.
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Disclosure: Dr. Esler reports research funds and is a consultant and on the speaker’s bureau for Ardian and Medtronic. Dr. Sobotka is an employee of Medtronic.
We now have two valuable pieces of information. One, we now know that patients defined as nonresponders actually are responders if you wait long enough. We do not necessarily understand why, but they do. Two, there is good proof of durability at least going out to 3 years. Beyond that we don’t know. Some people have projected that it could be as long as 10 years before those nerves grow back. At least now we have assurances that at 3 years it will happen. My conjecture is that depending on how good a job the denervation procedure does, it would not shock me if they remained denervated for 10 years. In fact, it would shock me if it was less than 5 years. That would tell me that the nerves were either not fully ablated, or that they were growing back faster than would be expected.
– George Bakris, MD
Endocrine Today Editorial Board member