9.2 Current Status of Renal Denervation to Treat Hypertension

These proceedings summarize the educational activity of the 16th Biennial Meeting of the International Andreas Gruentzig Society held January 31-February 3, 2022 in Punta Cana, Dominican Republic

Faculty Disclosures     Vendor Acknowledgments

2022 IAGS Summary Document

Statement of the problem or issue

Hypertension remains the leading cause of cardiovascular morbidity and mortality throughout the world. Approximately 30% of adults worldwide and up to 50% of adults in the United States (US) currently suffer from hypertension. Current US national guidelines for target systolic blood pressure are now set at 130 mm Hg. This value is based on compelling data from the SPRINT trial.¹ Furthermore, it turns out that as little as 10 mm Hg reduction in systolic blood pressure yields substantial reduction in risks of stroke, heart attack, and death. One of the biggest challenges is that only 30%–40% of all individuals with hypertension are currently achieving guideline-based blood pressure reduction. Some of this is due to failure to recognize the presence of hypertension, in other cases it is inadequate prescription of medications, and in many other cases it is related to medication noncompliance, which remains a profound problem. Given all these challenges in medication treatment for hypertension, there is a potential role for device-based blood pressure management (renal denervation; RDN). Safe and effective device-based therapies could provide potentially useful alternative treatments that may lower blood pressure successfully.

Gaps in our knowledge

Renal denervation attempts to disrupt sympathetic nerve flow from the kidney to the medulla of the brain stem (afferent signal) and also inhibits efferent nerve fibers from brain stem to kidney. The efferent nerves are important in the release of renin as well as aldosterone. Recent data from a pivotal, randomized, sham-controlled study has shown meaningful BP reduction that is observable over the entire 24 hours of a day (the “always on” phenomenon).² The gaps in our knowledge in RDN relate to questions of efficacy. There are now small, randomized, sham-control trials and a large meta-analysis showing efficacy of RDN,³ but the results from the largest pivotal trial (On-Medication) are still pending. Other questions remain as to the best technique for RDN, which include radiofrequency (RF) thermal ablation, thermal ablation with ultrasound, and chemical ablation. The longer-term efficacy and safety of these various techniques have not yet been fully defined, although data are accumulating. One of the more intriguing gaps in our knowledge is the issue of “nonresponders,” and whether we can determine by upfront testing who will get the best blood pressure lowering response following RDN. Finally, there are still questions about the optimal population who may benefit from this therapy, if and when it is FDA approved.

Possible solutions

We await the results of the ongoing large pivotal trial from Medtronic (SPYRAL HTN-ON MED, NCT02439775). These data will be extremely helpful in establishing the safety and efficacy of RF RDN. Other studies that are currently underway include large randomized trials using thermal ablation with ultrasound (RADIANCE-HTN, SOLO and TRIO Cohorts, ReCor Medical, NCT02649426), and chemical RDN with alcohol using the Peregrine system from Ablative Solutions (TARGET BP 1, NCT02910414). Additional technologies developed in the future to assist with RDN may include direct nerve sensing and/or stimulation, which might help predict patients who will get better responses, as well as quantifying the precise degree of denervation achieved by the procedure. Finally, there are some intriguing early data regarding genetic testing, which may eventually enable providers to select RDN for individuals identified to be the “best responders” to RDN.  If the currently ongoing randomized trials demonstrate good safety and efficacy, it is believed that RDN can become an important tool in the management of patients with poorly controlled hypertension.

References

1. The SPRINT research group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015;373(22):2103-2116. doi:10.1056/NEJMoa1511939

2. Bohm M, Kario K, Kandzari D, et al. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicenter, randomized, sham-controlled trial. Lancet, 2020; 395(10234):1444-1451. doi:10.1016/S0140-6736(20)30554-7

3. Ahmad Y, Francis DP, Bhatt DL, Howard JP. Renal denervation for hypertension. A systematic review and meta-analysis of randomized, blinded, placebo-controlled trials. JACC Cardiovasc Interv. 2021;14:2614-2624. doi:10.1016/j.jcin.2021.09.020