SYMPLICITY HTN-3 presented: Renal denervation misses primary efficacy endpoint
WASHINGTON — Confirming a preliminary press release from January, the SYMPLICITY HTN-3 trial failed to show benefit of renal denervation for the primary efficacy endpoint in patients with severe resistant hypertension compared with a sham procedure, according to data presented here.
As reported earlier, the renal denervation system (Symplicity, Medtronic) was found safe; the trial’s primary safety endpoint of a composite of major adverse events within 30 days or new renal artery stenosis of more than 70% within 6 months compared with an objective performance criterion of 9.8% was met in both arms (renal denervation, 1.4%; P<.001; sham procedure, 0.6%).
However, the big news was the primary efficacy endpoint — change in office systolic BP at 6 months — as there had been a lot of anticipation that catheter-based renal denervation could provide a new therapeutic option for patients with resistant hypertension, and the SYMPLICITY HTN-3 trial was the first sham-controlled randomized trial to assess the strategy.
Deepak L. Bhatt
Data presented by Deepak L. Bhatt, MD, MPH, executive director of interventional cardiovascular programs, Brigham and Women’s Hospital Heart and Vascular Center, Boston, and co-principal investigator, indicated that the primary endpoint did not significantly differ between groups (renal denervation, –14.13 ± 23.93 mm Hg vs. sham procedure, –11.74 ± 25.94 mm Hg; P<.001 for both comparisons; P for difference=.26).
Similarly, the secondary efficacy endpoint — change in mean 24-hour ambulatory systolic BP — was comparable between groups, with a reduction of –6.75 ± 15.11 mm Hg reported in the renal denervation arm and –4.79 ± 17.25 mm Hg in the sham-procedure arm (P for superiority=.98).
“These results underscore the importance of blinding and sham controls in evaluations of new devices, and have ramifications that go beyond interventional cardiology,” said Bhatt, who is also Chief Medical Editor of Cardiology Today’s Intervention. “Further study in rigorously designed clinical trials will be necessary and indeed warranted to confirm previously reported benefits of renal denervation in patients with resistant hypertension or to validate alternate methods of renal artery denervation.”
Potential study limitations Bhatt highlighted include drug adherence, which was not measured by blood levels, but by patient diaries at baseline and 6 months; the occurring medication changes; the duration of the primary efficacy endpoint, which may have been too short; operator learning curve; and biological confirmation of denervation, which did not occur.
The prospective, single blind, randomized, sham-controlled SYMPLICITY HTN-3 trial included 535 patients who were randomly assigned 2:1 to renal denervation (n=364) or a sham-based procedure (n=171). Patients had severe resistant hypertension (office systolic BP ≥160 mm Hg based on an average of three BP readings). According to Bhatt, prior to randomization, patients were on a stable antihypertensive regimen comprised of maximally tolerated doses of at least three drugs, including a diuretic, with no changes to the regimen for a minimum of 2 weeks prior to screening and no expected changes for at least 6 months. – by Brian Ellis
For more information:
Bhatt DL. Session 451: Late-breaking clinical trials. Presented at: American College of Cardiology Scientific Sessions; March 29-31, 2014; Washington, D.C.
Disclosure: Bhatt reports receiving research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Roche, Sanofi Aventis and The Medicines Company and reports involvement in unfunded research for FlowCo, PLx Pharma and Takeda.