Medical policy: Renal Denervation for Uncontrolled Hypertension

Policy number: MP 1.166

Effective date: 4/1/2026

Policy

Radiofrequency ablation of the renal sympathetic nerves is considered medically necessary for individuals whose blood pressure remains above >130/80 mmHg despite use of three (3) or more antihypertensive medications from three classes (angiotensin‑converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, thiazide diuretics, and beta blockers) at maximally tolerated doses or with intolerance to antihypertensive medications whose blood pressure remains uncontrolled despite attempting lifestyle modifications (see Policy Guidelines).

Ultrasound ablation of the renal sympathetic nerves is considered medically necessary for individuals whose blood pressure remains above >130/80 mmHg despite use of three (3) or more antihypertensive medications from three classes (angiotensin‑converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, thiazide diuretics, and beta blockers) at maximally tolerated doses or with intolerance to antihypertensive medications whose blood pressure remains uncontrolled despite attempting lifestyle modifications (see Policy Guidelines).

Policy guidelines

Priority for renal denervation of the renal sympathetic nerves may be appropriately given to patients with higher cardiovascular risk (e.g., comorbidities of coronary artery disease, diabetes, prior transient ischemic attack/cerebrovascular accident, or chronic kidney disease) who may have the greatest benefit from blood pressure reduction.

The procedure should only be performed in experienced, specialized centers with multidisciplinary hypertension teams involving experts in hypertension and percutaneous cardiovascular interventions after shared decision‑making about the risks and benefits of treatment with the individual.

There is too little data to support the use of renal denervation for the following: stage 1 HTN, isolated systolic HTN, stage 4 or 5 chronic kidney disease, single kidney, kidney transplant recipients, or redo renal denervation in individuals who fail to respond to initial renal denervation.

Contraindications include pregnancy, fibromuscular dysplasia, stented renal artery, renal artery aneurysm, significant renal artery stenosis, known kidney or secreting adrenal tumors, and unaddressed causes of secondary hypertension.

Product variations

This policy is only applicable to certain programs and products administered by Capital Blue Cross and subject to benefit variations. Please see additional information below.

FEP PPO - Refer to FEP Medical Policy Manual.

Description/background

Uncontrolled hypertension

Recommendations for blood pressure generally target <130/80 mmHg, although blood pressure goal can vary (e.g., comorbidities, life‑expectancy). High blood pressure, or hypertension (HTN) is estimated to affect approximately 30% of the population in the U.S. It accounts for a high burden of morbidity related to stroke, ischemic heart disease, kidney disease, and peripheral arterial disease. An estimated 1 in 4 adults with hypertension have their hypertension under control, but the remaining 77% (93 million) remain uncontrolled. Uncontrolled hypertension is diagnosed when an individual’s blood pressure remains above targeted levels (typically ≥140/90 mmHg) when a patient either is not using, or unable to use, treatments to control blood pressure or when hypertension persists despite antihypertensive therapies. The definition of uncontrolled hypertension is inclusive of resistant hypertension in which blood pressure remains above the targeted range despite the use of 3 or more antihypertensive medications, including a diuretic, with complementary mechanisms of action. A number of factors may contribute to uncontrolled hypertension including nonadherence to medications, excessive salt intake, inadequate doses of medications, excess alcohol intake, volume overload, drug‑induced hypertension, and other forms of secondary hypertension. Also, sometimes it is necessary to address comorbid conditions (i.e., obstructive sleep apnea) to control blood pressure adequately.

Radiofrequency denervation of the renal sympathetic nerves

Increased sympathetic nervous system activity has been linked to essential hypertension. Surgical sympathectomy has been shown to be effective in reducing blood pressure but is limited by the adverse events of surgery and was largely abandoned after effective medications for hypertension became available. The renal sympathetic nerves arise from the thoracic nerve roots and innervate the renal artery, the renal pelvis, and the renal parenchyma. Radiofrequency ablation (RFA) of the renal sympathetic nerves is thought to decrease both the afferent sympathetic signals from the kidney to the brain and the efferent signals from the brain to the kidney. This procedure decreases sympathetic activation, decreases vasoconstriction, and decreases activation of the renin‑angiotensin system.

The procedure is performed percutaneously with access at the femoral artery. A flexible catheter is threaded into the renal artery, and a controlled energy source, most commonly low‑power RF energy, is delivered to the arterial walls where the renal sympathetic nerves are located. Once adequate RF energy has been delivered to ablate the sympathetic nerves, the catheter is removed.

Ultrasound denervation of the renal sympathetic nerves

Ultrasound renal denervation (uRDN) is a minimally invasive procedure designed to treat hypertension by disrupting renal sympathetic nerves. The procedure targets the same physiological mechanism as radiofrequency ablation, aiming to decrease both afferent and efferent sympathetic signaling between the kidneys and the brain. This reduction in sympathetic activation is thought to decrease vasoconstriction and inhibit the renin‑angiotensin system, ultimately leading to blood pressure reduction.

The uRDN procedure is typically performed under local anesthesia with conscious sedation. Access is obtained through the femoral artery, and the catheter is advanced to the renal artery under fluoroscopic guidance. Once positioned, the catheter’s balloon is inflated with cooling fluid, and ultrasound energy is delivered. Usually, 2‑3 ultrasound emissions are delivered per renal artery, with the ability to treat both main renal arteries and accessory renal arteries when present.

Regulatory status

Two renal denervation devices have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of hypertension (FDA product code: QYI):

• Paradise^® Ultrasound Renal Denervation System (ReCor Medical, Inc.)

The Paradise^® Ultrasound Renal Denervation System (ReCor Medical, Inc.) was approved by the FDA on November 7, 2023 and the Symplicity Spyral™ Renal Denervation System (Medtronic, Inc.) was approved by the FDA on November 17, 2023. Both systems are indicated to reduce blood pressure as an adjunctive treatment in hypertension patients in whom lifestyle modifications and antihypertensive medications do not adequately control blood pressure.

No other renal denervation devices are currently FDA approved for the treatment of hypertension. Several other devices that were previously in development, such as the EnligHTN™ system (St. Jude Medical) and Vessix™ system (Boston Scientific), are no longer being marketed for this indication.

Rationale

For individuals who have uncontrolled hypertension, despite the use of anti‑hypertensive medications, who receive radiofrequency ablation (RFA) of the renal sympathetic nerves, the evidence includes several randomized controlled trials (RCTs), numerous systematic reviews of the RCTs, and a multinational registry study. Relevant outcomes are symptoms, change in disease status, morbid events, functional outcomes, and treatment‑related mortality. The range of effects seen with denervation is wide, reflecting different patient selection, degree of procedural completeness, and trial design. The SPYRAL HTN‑OFF MED study found that multielectrode renal denervation was superior to sham in the absence of background antihypertensive medication therapy, with between‑group differences of ‑4.0 mmHg for 24‑h SBP and ‑6.6 for office SBP at 3 months. The unpowered SPYRAL HTN‑ON MED pilot study also found significant between‑group differences of ‑7.4 mmHg for 24‑h SBP and ‑6.8 mmHg for office SBP at 6 months; however, results were only significant for the subgroup of patients non‑adherent to medications. Long‑term data from the SPYRAL HTN‑ON MED study suggest that blood pressure reductions with multielectrode renal denervation are progressive and sustained over time. The SPYRAL HTN‑ON MED Expansion study failed to meet its primary efficacy endpoint of a 0.03 mmHg difference between renal denervation and sham control groups at 6 months. Additional RCTs evaluating radiofrequency denervation are ongoing.

For individuals who have uncontrolled hypertension, despite the use of anti‑hypertensive medications, who receive ultrasound renal denervation (uRDN), the evidence includes 4 randomized sham‑controlled trials, 1 RCT comparing uRDN to radiofrequency‑based renal denervation, and a pooled analysis of 3 sham‑controlled RCTs. Relevant outcomes are change in blood pressure, medication use, and treatment‑related morbidity. Two trials, RADIANCE‑HTN SOLO and RADIANCE‑HTN TRIO evaluated uRDN in patients with no antihypertensive medication usage or 2 months post‑intervention. The RADIANCE‑HTN SOLO trial demonstrated that uRDN was superior to sham, with a between‑group difference of ‑6.3 mmHg for daytime ambulatory systolic blood pressure (SBP) at 2 months. RADIANCE‑HTN TRIO showed a ‑4.5 mmHg difference in daytime ambulatory SBP at 2 months. The durability of these effect was confirmed over 36 months of open‑label follow‑up, with significant reductions in office SBP from baseline seen with uRDN group. The REQUIRE trial, conducted in Asian populations, did not show a significant difference between uRDN and sham control, possibly due to study design limitations. Long‑term data from these trials show that blood pressure reductions with uRDN are sustained over time, although differences between uRDN and sham control groups diminished at 6 or 12 months after medication titration in some trials. FDA’s analysis of safety and effectiveness data from RADIANCE‑HTN TRIO and SOLO trials demonstrated improved outcomes in the uRDN group and acceptable safety. Collectively, the evidence suggests that uRDN may result in an improvement in net health outcomes for patients with uncontrolled hypertension despite the use of anti‑hypertensive medications.

Definitions/background

N/A

Disclaimer

Capital Blue Cross’ medical policies are used to determine coverage for specific medical technologies, procedures, equipment, and services. These medical policies do not constitute medical advice and are subject to change as permitted by law or applicable clinical evidence from independent treatment guidelines. Treating providers are solely responsible for medical advice and treatment of members. These policies are not a guarantee of coverage or payment. Payment of claims is subject to a determination regarding the member’s benefit program and eligibility on the date of service, and a determination that the services are medically necessary and appropriate. Final processing of a claim is based upon the terms of contract that applies to the member’s benefit program, including benefit limitations and exclusions. If a provider or a member has a question concerning this medical policy, please contact Capital Blue Cross’ Provider Services or Member Services.

Coding information

Note: This list of codes may not be all-inclusive, and codes are subject to change at any time. The identification of a code in this section does not denote coverage as coverage is determined by the terms of member benefit information. In addition, not all covered services are eligible for separate reimbursement.

Covered when medically necessary

References

1. Cluett JL, Blake O, Brown AL, et al. Renal Denervation for the Treatment of Hypertension: A Scientific Statement From the American Heart Association. Hypertension. Oct 2024; 81(10): e135-e148. PMID 39101202
2. Acelajado MC, Calhoun DA. Resistant hypertension, secondary hypertension, and hypertension crises: diagnostic evaluation and treatment. Cardiol Clin. Nov 2010; 28(4): 639-54. PMID 20937447
3. Centers for Disease Control and Prevention (CDC). Facts About Hypertension. Updated July 6, 2023; https://www.cdc.gov/bloodpressurefacts.htm. Accessed May 12, 2025.
4. Food and Drug Administration (FDA). Circulatory System Devices Panel. FDA Executive Summary, Premarket Application (PMA) for Pivotal Medtronic, Inc. Symplicity Spyral Renal Denervation System. 2023; https://www.fda.gov/media/171411/download. Accessed May 12, 2025.
5. Doumas M, Papademetriou V, Doumas S, et al. Benefits from treatment and control of patients with resistant hypertension. Int J Hypertens. Dec 22 2010; 2011: 318549. PMID 21234402
6. Zile MR, Little WC. Effect of autonomic modulation: more than just blood pressure. J Am Coll Cardiol. Mar 06 2012; 59(10): 910-912. PMID 22381426
7. Coppolino G, Pisano A, Rivoli L, et al. Renal denervation for resistant hypertension. Cochrane Database Syst Rev. Feb 21 2017; (2): CD011499. PMID 28220472
8. Sixtyvatch J, Smirt M, Phan MT, et al. Renal Denervation for Uncontrolled and Resistant Hypertension: Systematic Review and Network Meta-Analysis of Randomized Trials. J Clin Med. Feb 16 2021; 10(4). PMID 33669915
9. Ogoyama Y, Tada K, Abe M, et al. Effects of renal denervation on blood pressures in patients with hypertension: a systematic review and meta-analysis of randomized sham-controlled trials. Hypertens Res. Feb 2022; 45(2): 210-220. PMID 34657140
10. Papadopagli M, Covella M, Berra E, et al. Effectiveness of Renal Denervation in Resistant Hypertension: A Meta-Analysis of 11 Controlled Studies. High Blood Press Cardiovasc Prev. Jun 2018; 25(2): 167-176. PMID 29352063
11. Townsend RR, Mahfoud F, Kandzari DE, et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet. Nov 11 2017; 390(10108): 2160-2170. PMID 28859944
12. Bohm M, Kario K, Kandzari DE, et al. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet. May 02 2020; 395(10234): 1444-1451. PMID 32234634
13. Kandzari DE, Böhm M, Mahfoud F, et al. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet. Jun 09 2018; 391(10134): 2346-2355. PMID 29803589
14. Mahfoud F, Kandzari DE, Kario K, et al. Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial. Lancet. Apr 09 2022; 399(10333): 1410-1419. PMID 35390320
15. Kandzari DE, Kario K, Mahfoud F, et al. The SPYRAL HTN Global Clinical Trial Program: Rationale and design for studies of renal denervation in the absence (SPYRAL HTN-OFF MED) and presence (SPYRAL HTN-ON MED) of antihypertensive medications. Am Heart J. Feb 2016; 171(1): 82-91. PMID 26609604
16. Kario K, Mahfoud F, Kandzari DE, et al. Long-term reduction in morning and nighttime blood pressure after renal denervation: 36-month results from the SPYRAL HTN-ON MED trial. Hypertension. Jan 2023; 80(1): 280-288. PMID 36241705
17. Kandzari DE, Townsend RR, Kario K, et al. Safety and Efficacy of Renal Denervation in Patients Taking Antihypertensive Medications. J Am Coll Cardiol. Nov 07 2023; 82(19): 1809-1823. PMID 37914540
18. Townsend RR, Ferdinand KC, Kandzari DE, et al. Impact of Antihypertensive Medication Changes After Renal Denervation Among Different Patient Groups: SPYRAL HTN-ON MED. Hypertension. May 2024; 81(5): 1095-1105. PMID 38341554
19. Mahfoud F, Townsend RR, Kandzari DE, et al. Long-Term, Patient-Level Analysis of Radiofrequency Renal Denervation in the SYMPLICITY Clinical Trial Program. JACC Adv. Mar 2025; 4(3): 101606. PMID 39985884
20. Mahfoud F, Mancia G, Schmieder RE, et al. Outcomes Following Radiofrequency Renal Denervation According to Antihypertensive Medication Therapy. J Am Coll Cardiol. Aug 2023; 82(8): 1759-1770. PMID 37317686
21. Azizi M, Sharp ASP, Fisher NDL, et al. Patient-Level Pooled Analysis of Endovascular Ultrasound Renal Denervation or a Sham Procedure of 6 Months After Medication Escalation: The RADIANCE Clinical Trial Program. Circulation. Mar 05 2024; 149(10): 747-759. PMID 34775979
22. Azizi M, Daemen J, Lobo MD, et al. Twelve-Month Results From the RADIANCE-HTN SOLO Trial of Ultrasound Renal Denervation. JACC Cardiovasc Interv. Dec 2020; 13(24): 2922-2933. PMID 33357531
23. Rader F, Kritharides L, Wang Y, et al. Durability of blood pressure reduction after ultrasound renal denervation: three-year follow-up of the randomized RADIANCE-HTN SOLO Trial. Eur Heart J. Oct 2022; 43(18): 1677-1685. PMID 35913759
24. Azizi M, Mahfoud F, Weber MA, et al. Effects of Renal Denervation vs Sham in Resistant Hypertension after Medication Escalation. Prespecified Analysis at 6 Months of the RADIANCE-HTN TRIO Randomized Clinical Trial. JAMA Cardiol. Dec 01 2022; 7(12): 1244-1252. PMID 36350593
25. Kario K, Yook Y, Okumura K, et al. Catheter-based ultrasound renal denervation in patients with resistant hypertension: randomized, controlled REQUIRE trial. Hypertens Res. Feb 2022; 45(2): 221-231. PMID 34659405
26. McEvoy JW, McCarthy CP, Bruno RM, et al. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. Eur Heart J. Oct 07 2024; 45(38): 3912-4018. PMID 39321975
27. Barbato E, Azizi M, Schmieder RE, et al. Renal denervation in the management of hypertension in adults. A clinical consensus statement of the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. Apr 17 2023; 44(15): 1313-1330. PMID 36790101
28. Mancia G, Kreutz R, Brunström M, et al. 2023 ESH Guidelines for the management of arterial hypertension. The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens. Dec 01 2023; 41(12): 1874-2071. PMID 37345492
29. National Institute for Health and Care Excellence (NICE). Interventional procedures guidance: Percutaneous transluminal radiofrequency sympathetic denervation of the renal artery for resistant hypertension. IPG418. March 2012; https://www.nice.org.uk/guidance/ipg418. Accessed May 12, 2025.
30. Savienathan RW, East CA, Feldman DN, et al. SCAI Position Statement on Renal Denervation for Hypertension. Patient Selection, Operator Competence, Training and Technique, and Organizational Recommendations. J Soc Cardiovasc Angiogr Interv. 2023; 2(6Pt A): 101121. PMID 39129887