Symplicity Flex: Renal denervation misses primary endpoint in patients with mild hypertension

WASHINGTON — In the Symplicity Flex trial of patients with mild refractory hypertension, renal denervation failed to significantly lower BP compared with a sham procedure.

Steffen Desch, MD, reported at TCT 2014 that the mean change in 24-hour systolic BP at 6 months in an intention-to-treat cohort was –7 ± 10.6 mm Hg for patients treated with renal denervation using the Symplicity Flex catheter (Medtronic) compared with –3.5 ± 9.4 mm Hg for patients treated with a sham procedure (P=.15).

“If you look at the per-protocol group, however, it is a completely different story,” Desch, from University of Schleswig-Holstein, Campus Lübeck, Germany, said at a press conference.

In the per-protocol cohort, the mean change in 24-hour systolic BP at 6 months was –8.3 ± 8.9 mm Hg for patients treated with renal denervation compared with –3.5 ± 9.5 mm Hg for patients treated with the sham procedure (P=.042). The per-protocol cohort also had a significant decrease in daytime systolic BP after renal denervation compared with the sham procedure (–9.9 ± 9 mm Hg vs. –3.7 ± 9.9 mm Hg; P=.012).

The researchers observed no significant changes in mean 24-hour diastolic BP or nighttime BP between renal denervation and the sham procedure, and no major adverse events.

The Symplicity Flex trial included 71 patients with mild refractory hypertension who were randomly assigned to renal denervation (n=35) or an invasive sham procedure (n=36). Mild refractory hypertension was defined as daytime systolic BP of 135 mm Hg to 149 mm Hg and/or diastolic BP of 90 mm Hg to 94 mm Hg. All patients also received treatment with three or more antihypertensive agents, including one diuretic. The primary endpoint was change in 24-hour systolic BP at 6 months in the intention-to-treat cohort.

“This is the first randomized, sham-controlled study to [evaluate] a possible antihypertensive effect of renal denervation in patients with resistant hypertension yet only mildly elevated BP,” Desch said.

These findings suggest that renal denervation may be effective in patients with mild hypertension, although the exact mechanism is unclear, he said.

“You could argue that there might be fewer structural changes in these patients or that sympathetic overactivity might play a greater role,” he said during the press conference. “[These patients] might be younger or have less calcification. There are a number of arguments that could be made.”

Horst Sievert

Horst Sievert, MD, from the CardioVascular Center Frankfurt, Sankt Katharinen, Germany, and a presentation discussant, said he continues to perform renal denervation in his practice for select patients with resistant hypertension.

“These results are actually extraordinarily positive when you consider that this is a mild hypertension group,” Sievert said. “You can’t really expect more than what was achieved; otherwise, these patients could become hypotensive.” – by Jennifer Byrne

For more information:

Desch S. Plenary Session XXVI: Late-Breaking Clinical Trials #4. Presented at: TCT 2014; Sept. 13-17, 2014; Washington, D.C.

Disclosure: Desch reports no relevant financial disclosures. Sievert reports financial disclosures with several device and pharmaceutical manufacturers.