Radiofrequency renal denervation lowers BP despite missing primary efficacy endpoint
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CHICAGO — A radiofrequency renal denervation system lowered BP in patients with resistant hypertension already on antihypertensive medication at 6 months, but did not meet its primary efficacy endpoint.
David E. Kandzari, MD, chief of Piedmont Heart Institute and Cardiovascular Services in Atlanta, who presented the 6-month findings of the SPYRAL HTN-ON MED trial at the American Heart Association Scientific Sessions, told Healio that the radiofrequency renal denervation system (Symplicity Spyral, Medtronic) lowered office systolic BP in patients with resistant hypertension taking one to three BP medications compared with a sham procedure, but did not meet the trial’s primary efficacy endpoint of change in 24-hour ambulatory systolic BP compared with sham, likely due to changes that occurred among patients in the sham group.
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Unexpected results in sham group
“The efficacy results in the renal denervation arm were consistent with prior studies,” Kandzari told Healio. “The absolute reductions that were observed with ambulatory systolic blood pressure and that we achieved with office systolic blood pressure were very consistent and concordant with previous randomized trials. The discordance has to do with the term of statistical significance. The [ambulatory BP monitoring] result was not statistically different from the sham group, but the office systolic BP result was. The reason in part for this is ... what’s going on with the sham-controlled group in this study. What we identified is that there was a substantial change in medications prior to ascertainment of the primary endpoint at 6 months. Indeed, there was a 10-fold difference in changes in medications that would favor blood pressure lowering in the sham control group. We saw an unexpected reduction in blood pressure in the sham control group that we haven’t witnessed in previous studies.”
In a press release issued after the findings were presented, Medtronic announced it submitted the final module of its submission for FDA approval of the radiofrequency renal denervation system.
The trial included 337 patients (mean age, 55 years; 80% men) with office systolic BP of at least 150 mm Hg but less than 180 mm Hg who were stable on one to three medications for at least 6 weeks before enrollment, at which point they were assigned to renal denervation or a sham procedure.
The primary efficacy endpoint was change in 24-hour ambulatory systolic BP at 6 months; the secondary efficacy endpoints were frequentist analyses of 24-hour ambulatory systolic BP, office systolic BP, 24-hour ambulatory diastolic BP and office diastolic BP, a win ratio analysis and a medication burden analysis; and the primary safety endpoint was major adverse events at 1 month among patients in the renal denervation group of the present trial and the SPYRAL HTN-OFF MED trial.
At baseline, mean office systolic BP was 163 mm Hg, mean office diastolic BP was 101 mm Hg, mean 24-hour ambulatory systolic BP was 149 mm Hg and mean 24-hour ambulatory diastolic BP was 96 mm Hg, Kandzari said during the presentation.
The mean number of antihypertensive medications taken at baseline was 1.9, and the medication burden at baseline was 2.8 in the renal denervation group and 3 in the sham group, according to the researchers.
The rate of major adverse events at 1 month in the renal denervation group was 0.4%, and the upper one-sided CI of 1.9% beat the performance goal of 7.1% (P < .001), Kandzari said.
At 6 months, the mean number of medications used rose to 2.1% in the sham group but stayed at 1.9% in the renal denervation group (P = .01), whereas the medication burden rose from 3 to 3.5 in the sham group and from 2.8 to 2.9 in the renal denervation group (P = .04), according to the researchers.
In the frequentist efficacy analyses at 6 months, BP was reduced more in the renal denervation group than the sham group for the following metrics: 24-hour systolic ambulatory BP (difference, –1.9 mm Hg; P = .12), 24-hour diastolic ambulatory BP (difference, –0.8 mm Hg; P = .37), office systolic BP (difference, –4.9 mm Hg; P = .001) and office diastolic BP (difference, –2 mm Hg; P = .04), Kandzari said.
For the primary efficacy endpoint of 24-hour systolic ambulatory BP, the treatment difference was –0.03 mm Hg (95% Bayesian credible interval, –2.82 to 2.77) and the posterior probability of superiority was 50.8%, which did not meet the Bayesian threshold for success of 97.5%, he said.
Benefits demonstrated
“Despite the trial not meeting its primary endpoint because ... there was a reduction in the sham group for [ambulatory BP monitoring], the trial was highly positive in the reduction of office blood pressure at 6 months,” Kandzari told Healio. “But it was also significant to demonstrate that there was a win with renal denervation therapy with regard to the opportunity to either reduce ambulatory blood pressure or reduce the medication burden. And the therapy proved to be exceptionally safe.”
The full cohort consisted of 80 patients from the pilot study and 257 patients from the expansion study, and among those in the expansion study, those assigned to the sham group had many more medication changes than those assigned renal denervation (P < .0001), Kandzari said, noting that the same was not true for those in the pilot study (P = 1) and that the differences were most pronounced in the Black Americans subgroup (P = .003).
“The medication changes impact the ambulatory blood pressure more than the office blood pressure because per protocol ... we asked the patients not to take their blood pressure medications that morning [before an office visit],” Kandzari told Healio.
The win ratio of 1.5 favored the renal denervation group (P = .005), according to the researchers.
“The next steps are to expand the experience with renal denervation into broader, less selected patient populations more representative of real-world clinical practice,” Kandzari told Healio. “The AFFIRM trial, which is ongoing, is a large, single-arm, 1,000-patient study that’s much more inclusive of a broader patient population and is powered for patients with chronic kidney disease, diabetes and isolated systolic hypertension. In parallel is gaining more information that would further refine both patient selection and level-setting expectations with renal denervation therapy.”
Reference:
- Medtronic. news.medtronic.com/2022-11-07-SPYRAL-HTN-ON-MED-study-demonstrates-meaningful-clinical-benefits-consistent-with-other-SPYRAL-HTN-renal-denervation-trials. Published Nov. 7, 2022. Accessed Nov. 10, 2022.
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Kandzari DE, et al. LB.09: Resistant hypertension: A pressure cooker. Presented at: American Heart Association Scientific Sessions; Nov. 5-7, 2022; Chicago (hybrid meeting).
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