The Lancet JUNE 09, 2018

Endovascular Ultrasound Renal Denervation to Treat Hypertension (RADIANCE-HTN SOLO)

Michel Azizi, et al.

Bottom Line

The RADIANCE-HTN SOLO trial demonstrated that endovascular ultrasound-based renal denervation significantly reduces daytime ambulatory systolic blood pressure compared to a sham procedure in patients with mild-to-moderate hypertension in the absence of antihypertensive medication.

Key Findings

1. At 2 months, patients receiving ultrasound renal denervation (uRDN) experienced a greater reduction in daytime ambulatory systolic blood pressure (SBP) compared to the sham group (-8.5 mmHg vs. -2.2 mmHg; baseline-adjusted between-group difference of -6.3 mmHg; 95% CI: -9.4 to -3.1, p=0.0001).

2. The blood pressure lowering effect of uRDN was maintained at 6 months, even with the addition of standardized stepped-care antihypertensive medication, showing a baseline-adjusted difference of -4.3 mmHg (95% CI: -7.9 to -0.6, p=0.024) in favor of uRDN.

3. At 12 months, despite study unblinding, patients in the uRDN group required fewer antihypertensive medications to maintain blood pressure control compared to the sham group (mean 0 vs. 1.4 medications, p=0.015).

4. No major adverse events, such as renal artery injury or renal failure, were reported in either group through the initial follow-up periods.

Study Design

Design

RCT

Single-Blind

Sample

146

Patients

Duration

36 mo

Median

Setting

Multicenter, international

Population Patients with combined systolic-diastolic hypertension who were not taking, or were withdrawn from, antihypertensive medications.

Intervention Endovascular ultrasound renal denervation using the Paradise system

Comparator Sham procedure

Outcome Change in daytime ambulatory systolic blood pressure at 2 months

Study Limitations

• The study had a relatively small sample size, which limits the power to detect rare long-term safety events.

• The trial was conducted in a specialized setting with highly selected patients, potentially limiting the generalizability of results to broader, more complex clinical populations.

• The unblinding of patients and physicians after the 6-month primary endpoint may have introduced bias in subsequent medication management and blood pressure assessment.

• The study focused on a specific ultrasound-based device, and findings may not be directly extrapolatable to other renal denervation modalities or energy sources.

Clinical Significance

This trial provides robust evidence that ultrasound-based renal denervation is an effective and safe adjunctive therapy for reducing blood pressure and potentially decreasing the medication burden in patients with hypertension.

Historical Context

Following the controversial findings of the SYMPLICITY HTN-3 trial, which failed to show a significant blood pressure benefit from first-generation radiofrequency renal denervation, the RADIANCE-HTN trials were designed with more rigorous sham controls and standardized protocols to re-evaluate the efficacy of next-generation device-based renal denervation.

Guided Discussion

High-yield insights from every perspective

Med Student

Medical Student

Describe the physiological role of the renal sympathetic nerves in blood pressure regulation and explain the mechanism by which ultrasound renal denervation aims to lower blood pressure.

Key Response

Renal sympathetic efferent nerves stimulate renin release, increase sodium reabsorption, and decrease renal blood flow, while afferent nerves signal to the central nervous system to increase systemic sympathetic tone. Ultrasound renal denervation uses thermal energy to selectively ablate these nerves in the adventitia of the renal arteries, thereby interrupting the feed-forward cycle of sympathetic overactivity that drives many forms of hypertension.

Resident

The RADIANCE-HTN SOLO trial focused on patients with mild-to-moderate hypertension who were off medication. How does this study population differ from the 'resistant hypertension' populations of earlier trials like SYMPLICITY HTN-3, and why is this distinction important for clinical application?

Key Response

By studying patients off medications, RADIANCE-HTN SOLO eliminated the significant confounder of medication non-adherence, which plagued earlier trials. While resistant hypertension patients (on 3+ drugs) are the traditional targets, demonstrating efficacy in a simpler, drug-free cohort provides 'proof-of-concept' that the procedure itself—not just changes in pill-taking behavior—is responsible for the blood pressure reduction.

Fellow

Evaluate the technical advantages of ultrasound-based denervation used in RADIANCE over the first-generation radiofrequency (RF) systems. How might circumferential heating and penetration depth influence the consistency of the BP response?

Key Response

Ultrasound provides a circumferential, non-contact delivery of energy that can penetrate deeper into the adventitia (where nerves reside) more uniformly than point-by-point RF ablation. This potentially reduces the 'operator dependence' of the procedure and ensures a more complete denervation, which may explain the more consistent efficacy seen in the RADIANCE trials compared to earlier RF trials that lacked circumferential ablation consistency.

Attending

Considering the results of RADIANCE-HTN SOLO, how do you approach the 'patient preference' discussion for a 45-year-old with Grade 1 hypertension who is reluctant to start lifelong medication therapy?

Key Response

The trial suggests that renal denervation can provide an 'always-on' reduction in BP (roughly 8 mmHg daytime SBP). For patients with high treatment burden, side effects, or a strong preference for avoiding daily pills, this evidence supports discussing RDN as a legitimate alternative or adjunct to pharmacotherapy, emphasizing that while it may not eliminate the need for future drugs, it resets the baseline BP and mitigates the risks of non-adherence.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD

The RADIANCE-HTN SOLO trial employed a sham-control design with a 2-month primary endpoint. Critically analyze the limitations of this short-term endpoint regarding the potential for late placebo-effect attenuation or nerve regeneration.

Key Response

A 2-month window is excellent for capturing the immediate physiological impact of denervation while minimizing 'medication creep.' However, it cannot account for the long-term durability of the effect. Critics argue that sympathetic re-innervation or compensatory mechanisms (like the RAAS) might offset initial gains over years, requiring longitudinal data to confirm if the 2-month delta translates into a lifelong reduction in cardiovascular events.

Journal Editor

As a reviewer, how would you evaluate the impact of 'escape' medication protocols in RADIANCE-HTN SOLO on the interpretation of the primary efficacy endpoint?

Key Response

Reviewers look for the number of patients who had to restart meds for safety (BP >180/110) before the 2-month mark. If a higher proportion of the sham group required escape meds, the 'true' treatment effect of RDN might actually be underestimated because the sham group's average BP was lowered by those medications. Editors check if the trial used intention-to-treat analysis and how it handled these missing/rescued data points to ensure the results aren't biased.

Guideline Committee

Given the positive outcomes of the RADIANCE-HTN SOLO and the later RADIANCE TRIO trials, what shift is required in the ESC or ACC/AHA guidelines regarding the 'Class of Recommendation' for renal denervation?

Key Response

Current guidelines (like the 2023 ESH guidelines) have moved RDN to a Class IIb recommendation for patients with resistant hypertension or those who cannot tolerate drugs. The high-quality sham-controlled evidence from RADIANCE-HTN SOLO justifies moving RDN from an 'experimental' status to a 'shared decision-making' option, specifically highlighting ultrasound RDN as having a more robust evidence base for efficacy than earlier technologies.

Clinical Landscape

Noteworthy Related Trials

2014

SYMPLICITY HTN-3

n = 535 · NEJM

Tested

Radiofrequency renal denervation

Population

Patients with resistant hypertension

Comparator

Sham procedure

Endpoint

Change in office systolic blood pressure at 6 months

Key result: The trial failed to show a significant benefit in blood pressure reduction compared to the sham procedure.

2018

SPYRAL HTN-OFF MED

n = 146 · Lancet

Tested

Radiofrequency renal denervation

Population

Patients with uncontrolled hypertension off antihypertensive medications

Comparator

Sham procedure

Endpoint

Change in 24-hour ambulatory systolic blood pressure at 3 months

Key result: Renal denervation provided a statistically significant and clinically relevant reduction in blood pressure compared to sham control in the absence of medications.

2021

RADIANCE-HTN TRIO

n = 136 · Lancet

Tested

Ultrasound renal denervation

Population

Patients with resistant hypertension on standardized triple-drug therapy

Comparator

Sham procedure

Endpoint

Change in ambulatory daytime systolic blood pressure at 6 months

Key result: Ultrasound renal denervation significantly reduced daytime ambulatory systolic blood pressure compared to the sham procedure in patients with resistant hypertension.

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