New tools for hypertension: Catheter-based renal denervation devices bring hope, questions
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Key takeaways:
- After many years and multiple trials, two FDA-approved renal denervation systems are now available in the U.S.
- The devices treat people with persistent hypertension despite use of medications and diet.
Editor’s Note: This is part 1 of a two-part Healio Exclusive series on renal denervation for hypertension control. Part 2 can be viewed here.
Hypertension remains an outsized burden in the U.S. and globally, affecting one in three adults worldwide, with approximately four of every five of those adults not adequately treated, according to a recent WHO report.
The number of people living with hypertension, defined in the WHO report as a BP of at least 140 mm Hg systolic/90 mm Hg diastolic or taking medication for hypertension, doubled from 650 million in 1990 to 1.3 billion in 2019. Many adults struggle with resistant hypertension, defined as elevated BP above goal despite concurrent use of three or more antihypertensive medications of different classes, one of which is a diuretic, at maximal or maximally tolerated doses.
For those with difficult-to-control hypertension, a new, minimally invasive option is now available alongside lifestyle recommendations and medical therapy. In November, the FDA approved two renal denervation devices for people with uncontrolled hypertension despite maximally tolerated therapies, ushering in the first-ever interventional procedures with indications to lower BP.
“Hypertension is the most powerful and prevalent CV risk factor. It is more of a risk factor than the control of diabetes with HbA1c,” Keith C. Ferdinand, MD, the Gerald S. Berenson Endowed Chair in Preventive Cardiology, professor of medicine in the John W. Deming Department of Medicine at Tulane University School of Medicine and a member of the Healio | Cardiology Today Editorial Board, said during an interview. “Hypertension is more prevalent among people who self-identify as Black, affecting more than 50% to 60% of that population. Because of its potency and prevalence, we should not restrict our ability to control hypertension, a powerful risk factor.”
The first approved device, an ultrasound renal denervation system (Paradise, Recor Medical), lowers BP by denervating the sympathetic nerves surrounding the renal arteries, reducing the overactivity that can lead to hypertension. The second device approved by the FDA soon after, a radiofrequency renal denervation system (Symplicity, Medtronic), similarly ablates the renal nerves with heat energy, leading to a drop in BP.
The procedure offers hope for patients with uncontrolled high BP after other options have failed, according to Ajay J. Kirtane, MD, SM, director of Columbia Interventional Cardiovascular Care.
“There are many patients with hypertension refractory to multiple medications, and with multiple hospitalizations and even prior CV events due to uncontrollable BP,” Kirtane told Healio. “To at least have some hope that we may be able to control their BP better is so gratifying. There are so many patients with BP that is uncontrolled despite the best efforts at lifestyle modification and medications. The approval of a renal denervation device offers clinicians the ability to offer a device-based adjunct to their care that may help them be better controlled.”
Experts, however, are quick to caution that denervating the sympathetic nerves is not a panacea for hypertension; patients should not expect to discontinue all antihypertensive medications after undergoing renal denervation. Not all patients respond to treatment, and debate continues regarding ideal candidates for the intervention.
“In most of the studies, the patients who were on multiple medicines had to remain on at least one or two medicines,” Ferdinand said. “What renal denervation may help do is simplify therapy by removing the need for at least one form of pharmacotherapy. The patient will still need combination therapy to control resistant hypertension. This is another alternative that we will have to try and control that 15% to 20% of persons with resistant hypertension.”
A critical gap in care
Naomi D.L. Fisher, MD, director of hypertension services and the hypertension specialty clinic at Brigham and Women’s Hospital, said up to half of patients prescribed medications for hypertension are not taking them. Fisher added that, for many people, lifestyle modification and standard care medical therapies are inadequate.
“The evidence is undeniable. Medical therapy just is not working,” Fisher told Healio. “We only have to look at control rates to see what a poor job we are doing with current therapies. Despite having multiple classes of drugs and dozens of affordable drug choices, our control rates are hovering around 25% in the U.S. Underlying this dismal statistic is the reality that many of our patients are not able to tolerate enough medications to control their BP.”
Fisher said there are many reasons for nonadherence, including real or perceived adverse events, multiple comorbidities that drive up pill burden, cultural decisions, and a lack of clear discussions between clinicians and patients.
“But multiple studies show that after 1 year, fewer than half of our patients are taking their antihypertensive medications as we prescribe them,” Fisher said. “There is this giant bucket of nonadherence, which underlies a lot of uncontrolled hypertension. Some people do take their medicines religiously, but their hypertension is still resistant to at least three medications. Those are the minority, and that is why we say ‘apparent’ resistant hypertension.”
Raymond R. Townsend, MD, FAHA, professor of medicine and director of the Hypertension Program at the Hospital of the University of Pennsylvania, said BP control with drugs alone often worsens over time. Many people, he said, simply cannot tolerate the drug regimens.
“People say, ‘If you can lower BP with meds, why not?’” Townsend told Healio. “We have to point out, we are not lowering it with meds. Who enrolls in a clinical trial? These are not generic Americans; these are motivated people.”
‘This is like cutting the phone lines’
Renal denervation is an emerging technology to address the ongoing problem of difficult-to-treat and resistant hypertension, but the concept is not a new one. It attracted much interest from researchers and industry in the early 2010s, until the failure of a pivotal trial of the first version of the Symplicity device in 2014. Thereafter, some companies abandoned their renal denervation programs and others redesigned their technologies to make them more effective.
“The current approach is percutaneous access, where the interventionalist feeds a catheter through the aorta into the right and left renal arteries to deliver energy,” Fisher said. “The energy is used to ablate renal sympathetic nerves that lie in the adventitia surrounding the renal arteries. The most widely tested devices use radiofrequency ablation or ultrasound energy as sources.”
Researchers have also studied the use of chemical renal denervation with alcohol, which data suggest could be a safe and feasible alternative to energy-based renal denervation. However, there are fewer studies assessing that technology, Fisher said.
Townsend said ablating the sympathetic renal nerves engages several mechanisms to lower BP.
“The renal nerves do three main things,” Townsend said. “When stimulated, they promote release of renin from the kidney. If you stimulate harder, they recover more sodium from what your kidneys are filtering, so there is less sodium in the urine. If you stimulate maximally, you will actually see the arteries constrict. We believe that when we ablate, however we do it, we are probably disengaging all three mechanisms to various degrees. The brain and the kidney talk to one another, so this is like cutting the phone lines. We are interrupting that process. That seems, in two out of three people, to provide a meaningful reduction in BP.”
Selecting optimal candidates
The FDA label indications for the two approved renal denervation devices are broad: Both state they are to be used for adults with hypertension not adequately controlled with lifestyle changes and medications. Those indications could potentially open the procedure up to large swaths of patients.
“There is a fear that the floodgates will open,” Fisher said. “I do not think that will happen. We have this new technology that, for a select group of patients, could be lifesaving. We always start with lifestyle recommendations. There is no replacement for exercise, maintaining healthy body weight, reducing dietary sodium and alcohol. These universal therapies always come first and should always continue no matter what else is added. Medications come next. We are looking at patients in whom all of these attempts have already been made.”
Ferdinand said it remains unclear who are ideal candidates for renal denervation.
“The ideal candidates for renal denervation have yet to be realized,” Ferdinand said. “It will likely be patients with good adherence and BP poorly controlled despite being prescribed two or perhaps three medications at optimal doses, one of which should be a thiazide-type diuretic. In these patients, the renal nerve catheter does not remove the need for pharmacotherapy. But it will help simplify therapy and, along with combination pills, perhaps give more consistent BP control in the long term, with less difficulty maintaining appropriate adherence.”
In August, the Society for Cardiovascular Angiography and Interventions (SCAI) released a position statement on renal denervation, emphasizing patient selection, optimal techniques, competence, training and institutional recommendations. In 2020, the European Society of Hypertension (ESH) published a consensus statement on renal denervation in the Journal of Hypertension, stating the need for a structured process that ensures the appropriate performance of the procedure and adequate selection of hypertensive patients.
“The latter should also incorporate patients’ perspective and preference that needs to be respected in a shared decision-making process,” the position paper notes.
The ESH and SCAI guidelines both list renal denervation as a class 2b indication for people with uncontrolled BP despite therapy or if therapy is causing adverse events or poor quality of life.
“The guidelines are coming together regarding this second group of patients, recommending that renal denervation is not just for patients with resistant hypertension,” Fisher said.
Ferdinand said renal denervation will not eliminate the need for antihypertensive medicines for many patients with more difficult-to-treat or resistant hypertension.
“Patients should recognize that there is no one approach and most patients will be continued on an antihypertensive regimen, even if simplified or reduced by this innovative approach,” Ferdinand said. “With any new therapy or device, we should never over-promise results and at the same time ensure any beneficial effects are applied with health equity in mind, overcoming barriers to availability and costs.”
Editor’s Note: Part 2 of this Healio Exclusive series will discuss the questions that remain about renal denervation, including the durability of effect.
We want to hear from you:
Healio wants to hear from you: Who might be ideal candidates for renal denervation? What are your concerns? 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:
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.
Ajay J. Kirtane, MD, SM, can be reached at ak189@cumc.columbia.edu; X (Twitter): @ajaykirtane.
Raymond R. Townsend, MD, FAHA, can be reached at townsend@upenn.edu.
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