Renal Denervation Lowers BP Across High-risk Groups: Global SYMPLICITY Registry
“I think we are very close to clinical adoption of these technologies,” Felix Mahfoud says.
Blood pressure reductions in the 3 years after renal denervation are relatively consistent across various patient subsets with uncontrolled hypertension and high cardiovascular risk, according to an analysis of the Global SYMPLICITY Registry.
In the overall cohort, the average reduction in 24-hour systolic BP from baseline was 8.9 mm Hg, researchers led by Felix Mahfoud, MD (Saarland University Hospital, Homburg/Saar, Germany), report in a study published online ahead of the June 16, 2020, issue of the Journal of the American College of Cardiology.
Consistent drops averaging 8.6 to 10.4 mm Hg were seen across high-risk subgroups, including older patients and those with resistant hypertension, type 2 diabetes, isolated systolic hypertension, chronic kidney disease, and A-fib (P < 0.0001 for all). In addition, sustained falls were seen in patients at all baseline levels of atherosclerotic cardiovascular disease (ASCVD) risk.
These data can complement those from the recent sham-controlled trials that have demonstrated the safety and efficacy of renal denervation, Mahfoud indicated, pointing out that the trials were conducted in somewhat “artificial” groups of patients who were not taking any antihypertensive drugs or only one to three medications. “This is not the patient population . . . that will very likely be treated with this technology,” he told TCMTD.
Instead, denervation will likely be used primarily in patients with high CV risk taking several medications, a group well represented in the Global SYMPLICITY Registry. “This is the kind of real-world, more clinically relevant scenario than what we have seen in the very well-defined clinical studies that we completed, so I think that adds a lot to the profile of renal denervation and to the clinical picture we are trying to frame it in,” Mahfoud said.
Global SYMPLICITY Registry
The most recent sham-controlled trials in renal denervation—including RADIANCE-HTN SOLO, SPYRAL HTN-ON MED, SPYRAL HTN-OFF MED (pilot), and SPYRAL HTN-OFF MED (pivotal)—established the safety and efficacy of the procedure in relatively low-risk patients with uncontrolled hypertension, Mahfoud et al note, but it’s unclear whether the response would be similar in patients with either high CV risk or a condition associated with increased sympathetic activity, like diabetes, congestive heart failure, chronic kidney disease, obstructive sleep apnea, or arrhythmias.
The Global SYMPLICITY Registry, which includes those types of patients, is an ongoing multicenter registry with a planned enrollment of 3,000 and follow-up lasting 3 years. As of March 2019, 2,652 patients had been enrolled at 196 centers in 45 countries; 99.8% had a history of hypertension. Renal denervation was performed using either the Symplicity Flex or Symplicity Spyral radiofrequency catheter (both Medtronic).
I think we can now state that denervation lowers blood pressure. Felix Mahfoud
Reductions in BP obtained on 24-hour ambulatory monitoring and in the office were seen by the 6-month mark and then sustained out to 3 years. For 24-hour systolic BP, 3-year reductions from baseline were seen across high-risk groups, including patients 65 and older (8.7 mm Hg) and those with resistant hypertension (10.4 mm Hg), type 2 diabetes (10.2 mm Hg), isolated systolic hypertension (8.6 mm Hg), chronic kidney disease (10.1 mm Hg), and A-fib (10.0 mm Hg).
The investigators divided patients according to baseline ASCVD risk using the American Heart Association/American College of Cardiology calculator (< 10%, 10% to < 20%, and 20% or more) and found that BP declined after denervation in all of the groups. At 3 years, the drops in 24-hour systolic BP were 8.6, 6.0, and 7.6 mm Hg across the three risk groups, respectively, with no significant differences in the effect size between groups.
In post hoc subgroup analyses, reductions in systolic BP were generally similar in older versus younger patients and in those with versus without isolated systolic hypertension, A-fib, or diabetes.
As expected, rates of death, CV death, and hospitalization for new-onset heart failure or A-fib were elevated in patients with the highest baseline ASCVD risk. “But even in that patient population, we do see significant falls in blood pressure over time, and this may translate into improved outcomes over time,” Mahfoud said.
Patients with diabetes had higher risks of MI, end-stage renal disease, elevated creatinine levels, death, and CV death. All-cause mortality was more frequent in patients with A-fib, and CV death was more common in patients with isolated systolic hypertension.
“Future studies should assess the efficacy of renal denervation to prevent major adverse cardiovascular events in patients with isolated systolic and other specified forms of hypertension,” the authors say.
Chasing the ‘Holy Grail’
In an accompanying editorial, Stephen Textor, MD (Mayo Clinic, Rochester, MN), points out that the recent sham-controlled trials, though positive, have reported only short-term results and were modest in both size and antihypertensive effect.
Major concerns around renal denervation, he says, center on patient selection to optimize BP-lowering effects, durability of the effects, and methods to evaluate the technical success of the procedure.
Nonetheless, these new data “reaffirm the potential for renal denervation to achieve sustained, moderate systolic BP reductions, consistent with the more recent preliminary reports using somewhat different technologies for denervation,” Textor says, noting that some patients in the registry had reductions of systolic BP exceeding 30 to 40 mm Hg through 3 years. “Although these were not universally achieved, these data are consistent with occasional patients that have major BP reductions and can reduce antihypertensive drug requirements after renal denervation.”
Textor says, however, that it remains unclear how to identify the patients who are likely to derive clinically important benefits from denervation: “Identifying the truly optimal candidates for renal denervation remains the unresolved ‘holy grail’ for this technology.”
According to Mahfoud, investigators “are trying hard to identify predictors of response,” acknowledging that the current analysis doesn’t help in that regard since reductions in BP were seen across high-risk groups. Research is also ongoing to try to develop methods for determining when denervation has been achieved in the cath lab, he added.
Pending answers to those questions, “I think we are very close to clinical adoption of these technologies,” Mahfoud said. “I think we can now state that denervation lowers blood pressure. That statement is evidence-based given the results of the recent independently powered sham-controlled trials, and the first pivotal study that has been published in the meantime. It appears to be safe. And now we are working on identifying the best patient cohort, or the patient cohort with the highest benefit after denervation.”
Mahfoud F, Mancia G, Schmieder R, et al. Renal denervation in high-risk patients with hypertension. J Am Coll Cardiol. 2020;75:2879-2888.
Textor SC. Renal denervation and international registry data: where are we now? J Am Coll Cardiol. 2020;75:2889-2891.
- The Global SYMPLICITY Registry is funded by Medtronic.
- Mahfoud reports receiving support from Deutsche Gesellschaft für Kardiologie and Deutsche Forschungsgemeinschaft; and having received speaker honoraria from Medtronic and ReCor.
- Textor reports no relevant conflicts of interest.