Renal Denervation in Black Patients: SYMPLICITY HTN 3 Reassures at 36 Months

WASHINGTON, DC—Despite an initial hint to the contrary, Black patients with uncontrolled hypertension seem to benefit from renal denervation to the same extent as non-Black patients by 3 years, according to new subgroup data from SYMPLICITY HTN-3.

The trial, which showed a sustained drop in blood pressure with catheter-based renal denervation compared with a sham procedure at 3 years, had initially failed to meet its primary endpoint at 6 months. Moreover, 6-month subgroup data demonstrated that the procedure might not be as effective in Black patients compared with non-Black patients.

Deepak Bhatt, MD, MPH (Icahn School of Medicine at Mount Sinai, New York, NY), told the audience at this weekend’s CRT 2023 meeting that, back in 2014, he was initially hesitant to place any emphasis on the subgroup findings. “I didn’t want to accidentally steer the field into thinking that the procedure worked in white patients but not in Black patients,” he explained. “As it turns out, really with this longer-term follow up, I think we can say it does work in both types of patients.”

Any differences in outcomes that were noticeable at 6 months likely had to do with adherence to and complexity of medication regimens, he said during his presentation, noting that studies have also shown that hypertension control differ by race. In fact, researchers had originally stratified patients by race based on the possibility “that there would be a potentially greater treatment effect in Black patients,” said Bhatt, “not a lesser effect as we actually observed at the 6-month time point.”

“Assuming renal denervation does get approved, I don’t think we should not use it in Black patients because of that NEJM subgroup plot,” Bhat said, referring to the SYMPLICITY HTN-3 trial’s original publication. “I think that would be an error.”

Panelist Sripal Bangalore, MD (NYU School of Medicine, New York, NY), said this situation is one of the main reasons why subgroup analyses deserve to be interpreted with caution. “I'm glad we didn't conclude that it doesn't work in Blacks, because these are patients which are very difficult to treat,” he said.

Similarly, session co-moderator David Kandzari, MD (Piedmont Heart Institute, Atlanta, GA), told TCTMD these 3-year data confirm what was recently shown in the SPYRAL HTN-ON Med trial, in that “a reflexive interpretation of the data would be that perhaps there's no benefit in Black American patients.” That would be a “misperception,” he continued. Rather, “there seem to be unique differences with regard to prescription patterns and perhaps medication adherence.”

In another presentation at CRT 2023, Raymond Townsend, MD (University of Pennsylvania, Philadelphia), showed that 55% of Black American controls in the SPYRAL HTN-On Med trial increased their medication burden between baseline and 6 months and none decreased (P = 0.0382). This was in contrast to what was seen for non-Black American patients as well as those outside the US, where there were no differences in medication burden between those who received renal denervation and a sham procedure.

All these questions and nuances will likely come up again when the US Food and Drug Administration tasks its advisory committee with reviewing the data as part of the approval process—a meeting expected to take place this year, Kandzari predicted.

‘Equally Efficacious’

For the analysis, Bhatt and colleagues assessed outcomes for Black patients, who made up 26% of the original SYMPLICITY HTN-3 cohort.

Like their non-Black counterparts, Black patients who received renal denervation saw significant reductions in office, ambulatory, and 24-hour systolic and diastolic BP each at 12, 24, and 36 months compared with those in the sham procedure arm. For change in office systolic BP, the primary endpoint for which the trial was powered at 6 months, the difference between device- and sham-treated Black patients at 3 years was just shy of 25 mm Hg, an even greater difference than that seen between groups in non-Black patients, at 21 mm Hg.

The proportion of Black patients with office systolic blood pressure falling below 150 mm Hg continued to increase between 6 and 36 months, a trend also seen in a small subgroup of patients in the sham arm who, by trial design, were eligible to cross over to receive renal denervation.

Safety was good overall, with no late emerging complications in those initially randomized to renal denervation or in patients who crossed over.

Bhatt acknowledged that while drug testing to gauge adherence to antihypertensive medications was not performed, patients were prescribed maximally tolerated doses.

“These results do corroborate the fact that we did see a signal in the non-Black patients at 6 months with a significant blood pressure reduction and now we see a significant reduction in patients irrespective of race,” he said.

Going forward, Bhatt would like to see similar trials do a better job of recruiting Asian and Hispanic patients, two cohorts which he could not comment on in this study due to lack of enrolled patients.

“These data are reassuring,” Bhatt concluded. “There's nothing race-specific about renal denervation and its effects. I think in the right patient population, which personally I think here is out-of-control blood pressure in which patients are maxed out on medicines and lifestyle, I think renal denervation is equally efficacious in Blacks and non-Blacks.”