Hypertension is associated with an increased risk of cardiovascular events and has a high prevalence rate in the United States. Unfortunately, roughly one half of hypertensive patients have sub-optimal control of their blood pressure. When untreated or undertreated, hypertension can lead to an array of complications including left ventricular hypertrophy, heart failure (both preserved and reduced ejection fraction), ischemic stroke, intracranial hemorrhage, ischemic heart disease, and chronic or end-stage kidney disease (Basile & Bloch, 2024).

Contemporary medication therapy for the treatment of hypertension can be inadequate to achieve blood pressure goals. Refractory hypertension is defined as blood pressure not at goal when a patient is taking at least three antihypertensive agents, from different drug classes (including a diuretic), prescribed at maximally tolerated dosages and frequency, with the exclusion of pseudoresistance of white coat hypertension and medication non-compliance. Similarly, patients who require four or medications to achieve blood control are classified as controlled refractory hypertension (Brook & Townsend, 2024).

Renal denervation (RDN) is an emerging therapeutic option for patients with refractory hypertension and even for those not currently on medication. RDN has been proven to be a safe and efficacious procedure that is gaining renewed interest after several recent sham-controlled trials demonstrated sustained lowering of blood pressure. RDN is a minimally invasive catheter-based procedure via the femoral artery utilizing radiofrequency or ultrasound intervention of the renal afferent and efferent nerves within the wall of the renal arteries. This results in a disruption of the signals between the kidney and the brain, which reduces sympathetic activity locally in the kidney and systemically that leads to a decrease in renin activity and increase renal perfusion (Marcusohn et al., 2023).  

RDN trials date back to 2014 with the SYMPLICITY HTN-3 that was a prospective, single-blind, randomized, sham-controlled trial enrolling patients with severe resistant hypertension using first-generation radiofrequency ablation devices. Initial 6-month data failed to show evidence of significantly lower blood pressure post-intervention. In 2022, however, 3-year follow up data of this trial demonstrated a decrease in office systolic blood pressure of 26.4 mm Hg in the treatment group versus 5.7 mm Hg in the sham group. There have been two additional trials with patients taking antihypertensive medications to help understand the role of RDN as adjunctive therapy. RADIANCE HTN TRIO trial was published in 2021 and was a randomized, international, multicenter, single-blind, sham-controlled trial that enrolled patients taking at least three antihypertensive medications utilizing ultrasound RDN. The results demonstrated a reduction in daytime ambulatory SBP of 8.0 mm Hg, compared to 3.0 mm Hg in the sham group. SPYRAL HTN-ON MED trial was published in 2022 and was also a prospective, randomized, sham-controlled, patient and assessor-blinded trial with patients prescribed one to three antihypertensive medications utilizing radiofrequency RDN. This trial showed significant blood pressure reductions with 20% lower medication burden at six months with RDN versus sham procedure. Both trials supported the use of RDN as effective adjunctive therapy with minimal safety events (Azizi et al., 2021; Mahfoud et al., 2022).

There have also been two noteworthy trials that enrolled patients who were not on antihypertensive medication to investigate the usefulness of RDN in blood pressure management in this population. RADIANCE HTN SOLO, published in 2018, was a multicenter, international, single-blind, randomized, sham-controlled trial implementing ultrasound RDN that demonstrated reduction daytime ambulatory systolic blood pressure at 2 months. A three-year follow up analysis showed a lasting reduction in office BP of 18 mm Hg from baseline to 36 months (Azizi et al., 2018; Rader et al., 2022). In 2020, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) was an international, prospective, single-blinded, sham-controlled trial that showed superiority of radiofrequency RND compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. There was a mean reduction in SBP and diastolic BP (DBP) of 4.7 mm Hg and 3.7 mm Hg respectively, compared to 0.6 mmHg and 0.8 mmHg in the sham group (Bohm et al., 2020).

In early 2023, the American College of Cardiology released a consensus statement regarding RDN supporting its use and encouraging a multidisciplinary team approach at centers that will offer this treatment. Then after more than a decade since the inception of the technology, the FDA approved both the radiofrequency and ultrasound RDN devices in the United States in November 2023. RDN may be the key to allow many patients to finally achieve optimal blood pressure control and overall reduce their risk of cardiovascular adverse events.

References: 

Azizi, M., Sanghvi, K., Saxena, M., Gosse, P., Reilly, J. P., Levy, T., Rump, L. C., Persu, A., Basile, J., Bloch, M. J., Daemen, J., Lobo, M. D., Mahfoud, F., Schmieder, R. E., Sharp, A. S. P., Weber, M. A., Sapoval, M., Fong, P., Pathak, A., Lantelme, P., … RADIANCE-HTN investigators (2021). Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial. Lancet (London, England), 397(10293), 2476–2486. https://doi.org/10.1016/S0140-6736(21)00788-1

Azizi, M., Schmieder, R. E., Mahfoud, F., Weber, M. A., Daemen, J., Davies, J., Basile, J., Kirtane, A. J., Wang, Y., Lobo, M. D., Saxena, M., Feyz, L., Rader, F., Lurz, P., Sayer, J., Sapoval, M., Levy, T., Sanghvi, K., Abraham, J., Sharp, A. S. P., … RADIANCE-HTN Investigators (2018). Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial. Lancet (London, England), 391(10137), 2335–2345. https://doi.org/10.1016/S0140-6736(18)31082-1

Basile, J. & Bloch, M. (2024, January 31). Overview of hypertension in adults. UpToDate https://www.uptodate.com/contents/overview-of-hypertension-in-adults

Böhm, M., Kario, K., Kandzari, D. E., Mahfoud, F., Weber, M. A., Schmieder, R. E., Tsioufis, K., Pocock, S., Konstantinidis, D., Choi, J. W., East, C., Lee, D. P., Ma, A., Ewen, S., Cohen, D. L., Wilensky, R., Devireddy, C. M., Lea, J., Schmid, A., Weil, J., … SPYRAL HTN-OFF MED Pivotal Investigators (2020). Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet (London, England), 395(10234), 1444–1451. https://doi.org/10.1016/S0140-6736(20)30554-7   

Brook, R. and Townsend, R. (2024, May 14). Treatment of resistance hypertension. UpToDate.  https://www.uptodate.com/contents/treatment-of-resistant-hypertension

Mahfoud, F., Kandzari, D. E., Kario, K., Townsend, R. R., Weber, M. A., Schmieder, R. E., Tsioufis, K., Pocock, S., Dimitriadis, K., Choi, J. W., East, C., D'Souza, R., Sharp, A. S. P., Ewen, S., Walton, A., Hopper, I., Brar, S., McKenna, P., Fahy, M., & Böhm, M. (2022). Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial. Lancet (London, England), 399(10333), 1401–1410. https://doi.org/10.1016/S0140-6736(22)00455-X  

Marcusohn, E., Tobe, S, Dueck, A., & Madan, M. (2023). Renal denervation for uncontrolled hypertension. Canadian Medical Association Journal, 195(43), E1475-E1480. https://www.doi.org/10.1503/cmaj.230745  

Rader, F., Kirtane, A. J., Wang, Y., Daemen, J., Lurz, P., Sayer, J., Saxena, M., Levy, T., Scicli, A. P., Thackeray, L., Azizi, M., & Weber, M. A. (2022). Durability of blood pressure reduction after ultrasound renal denervation: three-year follow-up of the treatment arm of the randomised RADIANCE-HTN SOLO trial. EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology, 18(8), e677–e685. https://doi.org/10.4244/EIJ-D-22-00305

Schmieder, R., Burnier, M., East, C., Tsioufis, K., & Delaney, S. (2023). Renal Denervation: A Practical Guide for Health Professionals Managing Hypertension. Interventional cardiology (London, England), 18, e06. https://doi.org/10.15420/icr.2022.38

 

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GUIDELINE SUMMARY	BLOG	NURSING SPECIALTY
Hypertension	Measuring Non-Invasive Blood Pressure Step by Step	Cardiac Nursing