It’s been a busy past year for renal denervation, and it’s set to hot up even more. The European Society of Hypertension (ESH) recently updated its guidelines at its annual meeting in June to recommend renal denervation as an adjunctive therapy to resistant hypertension.
Combined with a US Food and Drug Administration (FDA) Advisory Committee Meeting on 22-23 August 2023 to discuss what would be the first approval in the US for renal denervation devices, the treatment is currently in a crucial period.
But with a plethora of resistant hypertension treatments already available, will renal denervation become a practical option for patients?
Using high energy to destroy nerves might not be the most talked about treatment for reducing high blood pressure, but there is evidence that the catheter-based procedure works.
The procedure involves radiofrequency or ultrasound ablation of afferent and efferent nerves located in the renal artery that carry important signals to the brain that control blood pressure. Reducing the functionality of these pathways leads to various blood pressure-lowering mechanisms.
It’s a potential option for patients who don’t respond to blood pressure-lowering drugs, who make up approximately 20% of hypertension patients.
Whilst there are devices approved in Europe, there are currently no renal denervation systems that are approved for medical use in the US. However, Medtronic and ReCor are two companies that are eagerly awaiting the FDA verdict for their devices in August.
If approved by the FDA, it could potentially help open avenues for the therapy’s more widespread adoption by healthcare professionals.
The FDA hearing alone is a sign that renal denervation has come a long way from its ancestral beginnings in 1953 when the removal of renal nerves was first used as a treatment option for hypertension. Since then, it’s existed in somewhat of a limbo after decades of mixed sentiment and underwhelming results.
Randomised trials key in resurgence
One of the reasons the ESH supported renal denervation as a treatment option was due to several multi-centre, prospective, single-blind, randomised, controlled studies. The big-hitting trials were conducted by Medtronic and ReCor Medical, who both have renal denervation systems lined up for the FDA committee meeting.
“Since 2017, multiple sham-controlled trials using either ultrasound or radiofrequency-based renal denervation have consistently shown that renal denervation lowered consistently blood pressure in patients with hypertension either off-medications or on- medications,” Professor Michel Azizi, head of the Hypertension Excellence Center, Hôpital Européen, Georges Pompidou, Paris, France and an investigator of the RADIANCE trials, tells Medical Device Network.
“This led to new guidelines which approved renal denervation use for adjunct therapy to lifestyle measures and antihypertensive medications.”
Renal denervation systems have been around for a while – indeed Medtronic, ReCor, and Johnson & Johnson (J&J) all have CE-marked devices in Europe – but Professor Azizi said misplaced early hype around the systems and weakly designed trials hindered any meaningful early success.
“The main reason was the too rapid entry into the market and initial hype around the first unipolar SYMPLICTY catheter even though there were extremely heterogeneous results of the early trials up to 2015.”
“Subsequently, we learned where the renal nerves were more abundant to be ablated around the renal arteries. This led to improved catheter designs and improved procedures. Moreover, the trial designs were harmonised and improved relying on ambulatory blood pressure monitoring (ABPM) as the primary endpoint, which was not the case in the majority of the early trials.”
Medtronic produced mixed 2022 results for its Simplicity denervation system. The SYMPLICITY HTN-3 trial indicated that the system was no different from a sham procedure in reducing office and ambulatory blood pressure in patients with resistant hypertension. But at a final three-year follow-up, patients who originally received renal denervation demonstrated large reductions in blood pressure.
In another trial, SPYRAL HTN-ON MED, Medtronic missed the primary endpoint as measured by a change in blood pressure over 24-hour ambulatory monitoring. However, once again, patients did see a statistically significant reduction in office-based systolic blood pressure, which was the trial’s secondary endpoint.
Medtronic’s renal denervation race competitor, ReCor revealed results for its Paradise Ultrasound Renal Denervation system in February 2023. Results from the Radiance II trial, which were published in the Journal of the American Medical Association (JAMA), demonstrated the system met primary efficacy endpoints.
But theory and practice are very different principles, and questions are being asked about the cost and feasibility of the treatment in clinical practice.
Reimbursement and cost
Currently, reimbursement status varies between countries in Europe.
European healthcare systems can choose from Medtronic’s Simplicity Spyral system, ReCor Medical’s Paradise system, or J&J’s Renlane system, all of which are CE-marked. A Medtronic-funded 2023 review published in Interventional Cardiology, Review, Research and Resources stated that more trial results and subsequent FDA approval would help advance the reimbursement landscape in Europe. As usual, much of the therapy’s future depends on the FDA verdict in August.
GlobalData analyst Shabnam Pervez says that exact estimates of renal denervation costs are hard to ascertain due to the procedure’s ad hoc use. Results from a 2018 statistical model published in the American Journal of Hypertension estimated a total cost of $6430.
Pervez adds that the current model estimates are polarised but given the efficacy of the procedure and the resulting reduced risk of stroke, coronary disease, heart failure, and end-stage renal disease, costs are offset. It could be seen as “priceless” Pervez concludes.
Professor Azizi, who places the current cost of the procedure at around €4000-5000, says that costs should decrease as more procedures are conducted.
Azizi comments: “To the cost of the catheter, the environmental costs should be added (interventionalist, anaesthesiologist, one-day hospitalisation, access to the cath lab. However, the procedure is done once, and as such, should be compared to life-long treatment.
“Because of its long-term blood pressure-lowering effects and increased time-in target blood pressure range, renal denervation would be cost-effective in the highest risk patients over a lifetime horizon.”
Indeed, a 2012 study published in the Journal of the American College of Cardiology investigating the quality-adjusted life year (QALY) concurs. The study showed a QALY increase from 12.07 to 13.17 years. This led to a discounted incremental cost-effectiveness ratio of $3,071/QALY. The researchers concluded that renal denervation for resistant hypertension might not solely be cost-effective, it could even be cost-saving. They add that although there is a big outlay at the time of treatment, it seems to offer better value over time compared to other, well-accepted treatments.
Results from the bigger medical device players in the industry have helped a mini-resurgence for renal denervation. And although the issue of reimbursement in America will remain, August will be a landmark month for renal denervation.
When the FDA convenes to discuss approval for Medtronic’s and ReCor’s devices, whether the systems are approved or rejected will greatly influence the market’s future. A market, which, according to a model by GlobalData, could be worth nearly $500m by 2033.
Azizi says: “It is difficult to see in a crystal ball what the FDA’s decisions will be. Much evidence has been provided on the effectiveness of the RDN. We hope that the FDA will take it into account.”