Expectations vs. reality: How low can BP go after renal denervation?
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Key takeaways:
- Data show renal denervation safely lowers BP, but some question the durability of effect.
- Experts continue to research how to identify nonresponders to therapy.
Editor’s Note: This is part 2 of a two-part Healio Exclusive series on renal denervation for hypertension control. Part 1 can be viewed here.
The FDA approvals of two renal denervation devices for people with uncontrolled hypertension have been hailed by hypertension experts as a much-needed advance in the field; yet, questions remain about limitations of this type of therapy.
As real-world use of the two interventional devices begins — the FDA approved both ultrasound and radiofrequency renal denervation devices in November — uncertainties around the procedure remain. Among them are how to choose ideal candidates for renal denervation, determining who will respond to therapy and the cost effectiveness of denervating the sympathetic nerves.
Durability of effect
During two meetings of the FDA’s Circulatory System Devices Panel of the Medical Devices Advisory Committee in August, some panelists expressed concerns about a modest reduction in BP with the devices, as well as the potential for device overuse among clinicians.
Data from one of the studies Medtronic submitted to the FDA, SPYRAL HTN-ON MED, was cited by several panelists who expressed concerns about a small effect on BP lowering in adults with uncontrolled hypertension with BP medications continued during the trial. There was a nonsignificant 0.03 mm Hg ambulatory systolic BP reduction among participants in the renal denervation arm vs. sham controls, which did not meet the primary endpoint of significant change in 24-hour ambulatory systolic BP compared with a sham procedure.
Medtronic attributed those results to changes that occurred among patients in the sham group. Researchers identified a 10-fold difference in changes in medications that would favor BP lowering in the sham control group, which researchers said was an unexpected reduction not observed in previous studies.
“A lot of the disappointment came on the background of incredibly high expectations from the early trials, where systolic BP fell by 20 to 30 points,” Fisher said. “Many were expecting this blockbuster, dramatic fall in BP, which we have not seen since. It is important to look at the decreases we are getting, which are drops in ambulatory BP on the order of 5, 6, 7 mm Hg. That translates to a fall in office BP of about 10 points, which is the same degree of efficacy from a potent antihypertensive medication. Additionally, we know that a drop of office BP of 10 points translates to a 20% or so reduction in CV risk.”
Herbert D. Aronow, MD, MPH, FACC, FSCAI, FSVM, medical director of heart and vascular services and the Benson Ford Chair in Heart and Vascular at Henry Ford Health, agreed that small reductions in BP, even 2 mm Hg to 3 mm Hg, will likely translate into “substantial reductions” in risk for CV events, including MI and stroke.
“Based on the wealth of data we have on ultrasound and radiofrequency renal denervation, we have seen efficacy and safety in the short term and durability out to 3 years,” Aronow, also chair of the SCAI writing group behind the renal denervation position statement, told Healio. “From real-world registry data, we see continued effectiveness and no signal for harm up to 5 years out. The data in aggregate suggest durability.”
Unanswered questions
As real-world renal denervation use begins, there are still some unanswered questions about the procedure, according to experts.
“We have two problems,” Townsend said. “No. 1, one-third of patients do not respond to renal denervation and we do not who those people are. No. 2, when we denervate, we do not really know how thorough the denervation is. We put the catheter in, we ablate, we take the catheter out. Then, we wait 3 months to see what happened.”
Aronow agreed it would be helpful if interventionalists could immediately discern if a renal denervation procedure were successful. Such work is currently underway in research labs, but remains unavailable for clinical use, he said.
“Unlike other procedures we perform, with renal denervation we do not have real-time feedback,” Aronow said. “There is no point-of-care test, if you will, that indicates that the renal denervation procedure was or was not successful. We are relegated to watchful waiting. Either it worked or it did not work, and we won’t know right away.”
Another issue going forward will be cost-effectiveness, Aronow said.
“There have been early studies suggesting favorable cost effectiveness, mostly outside of the U.S., but we do not fully understand cost-effectiveness of renal denervation in the U.S.,” Aronow said. “It may turn out that it is cost-effective for a large proportion of patients with hypertension, or maybe it will end up that we should only consider this therapy for a small piece of the pie. From a value-based care standpoint, cost-effectiveness, including ascertainment of quality metrics, should guide our decisions.”
Data also suggest that renal denervation may have beneficial effects on other conditions associated with sympathetic imbalance, including sleep apnea, left ventricular hypertrophy, albuminuria, atrial fibrillation and even polycystic kidney disease. Those data could eventually open up the procedure to more patients, according to Ferdinand.
“There is some basic science that suggests renal denervation may affect cardiac arrhythmias,” Ferdinand said. “There may be benefits for people with impaired glucose intolerance and metabolic syndrome. And again, going back to race and ethnicity, if renal denervation improves outcomes across all populations, those who identify as Black would benefit, since they have more severe and highly prevalent hypertension.”
With two renal denervation devices now on the commercial market and post-marketing surveillance underway, Aronow said there has been a “resurgence” in interest around hypertension because of the emerging technologies.
That interest, Aronow said, should benefit everyone living with hypertension.
“This is a tremendous opportunity for us in the CV field because we have not been as successful as perhaps we could have been with the tools we have had up until now,” Aronow said. “To appropriately triage patients to renal denervation therapy, we need multidisciplinary collaboration. Only the minority of patients coming through hypertension specialty centers will need a renal denervation procedure, but it is the majority who will benefit from having done so. These efforts are going to up our game when it comes to hypertension management in general and serve a much broader population than just those who ultimately may end up having a renal denervation procedure.”
We want to hear from you:
Healio wants to hear from you: What are your thoughts on the durability of renal denervation for lowering BP? Have your patients asked about the procedure? Share your thoughts with Healio by emailing the author at rschaffer@healio.com or posting to X (Twitter) and tagging @CardiologyToday. We will contact you if we wish to publish any part of your story.
References:
- FDA briefing documents (Medtronic). https://www.fda.gov/media/171411/download. Published Aug. 23, 2023. Accessed Jan. 9, 2024.
- FDA briefing documents (Recor). https://www.fda.gov/media/171388/download. Published Aug. 22, 2023. Accessed Jan. 9, 2024.
- Medtronic briefing documents. Available at: https://www.fda.gov/media/171412/download. Published Aug. 23, 2023. Accessed Jan. 9, 2024.
- Recor briefing documents. Available at: https://www.fda.gov/media/171397/download. Published Aug. 22, 2023. Accessed Jan. 9, 2024.
- Schmieder RE, et al. J Hypertens. 2021;doi:10.1097/HJH.0000000000002933.
- Swaminathan RV, et al. J Soc Card Angio Interv. 2023;doi:10.1016/j.jscai.2023.101121.
- WHO. Global report on hypertension. https://www.who.int/teams/noncommunicable-diseases/hypertension-report. Published Sept. 19, 2023. Accessed Jan. 9, 2024.
For more information:
Herbert Aronow, MD, MPH, FSCAI, can be reached at haronow1@hfhs.org; X (Twitter): @herbaronowmd.
Keith C. Ferdinand, MD, can be reached at kferdina@tulane.edu; X (Twitter): @kcferdmd.
Naomi D.L. Fisher, MD, FTOS, can be reached at nfisher@bwh.harvard.edu.
Raymond R. Townsend, MD, FAHA, can be reached at townsend@upenn.edu.
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