Renal denervation: An adjunct for treating drug-resistant hypertension?

Ultrasound renal denervation (RDN) offers a blood-pressure (BP) lowering benefit for individuals with triple drug-resistant hypertension compared with a sham procedure, according to the RADIANCE-HTN TRIO trial presented at ACC.21.

Uncontrolled hypertension remains a major public health issue despite the availability of a variety of medications, noted coprincipal investigator Dr Ajay Kirtane from the New York-Presbyterian/Columbia University Irving Medical Center, New York, New York, US, in a press release.

“Endovascular RDN reduces BP in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown … This study has shown for the first time that RDN can effectively [and safely] lower BP in patients in whom it is uncontrolled despite standardized treatment with three guideline-recommended medications,” said Kirtane.

At 2 months, the reduction in daytime ambulatory systolic BP (SBP) in the intention-to-treat (ITT) cohort was greater with RDN vs sham (–8.0 vs –3.0 mm Hg; median difference, –4.5 mm Hg; p_adjusted=0.02). A similar trend was observed in the per-protocol population (median difference, –5.4 mm Hg; p_adjusted=0.01) and in patients with complete ambulatory BP data (–5.8 mm Hg; p_adjusted=0.005). [Lancet 2021;doi:10.1016/S0140-6736(21)00788-1]

Median differences in other SBP parameters in the ITT cohort also favoured RDN over sham, including 24-hour ambulatory (–4.2 mm Hg; p_adjusted=0.02), night-time ambulatory (–3.9 mm Hg; p_adjusted=0.04), office (–7.0 mm Hg; p_adjusted=0.04), and home SBP (–4.0 mm Hg; p_adjusted=0.05).

The consistent SBP reductions with RDN reinforces the validity of the findings, noted the researchers. “Tipping-point analysis showed the results to be robust … The effect of RDN on the primary efficacy endpoint was consistent across sex, ethnicity, age, abdominal circumference, and baseline BPs.”

Of the three major adverse events (AEs) that occurred a month following RDN, only one was deemed procedure-related (access site pseudo-aneurysm) which successfully resolved with thrombin injection.

The study enrolled individuals (mean age 53 years, 80 percent male) with a mean office BP of 163/104 mm Hg at study entry despite being on a mean of four antihypertensive agents. Participants were switched from their existing medications to a standardized regimen comprising a single-pill, fixed-dose, daily combination of three* antihypertensives for 4 weeks. Following which, patients whose daytime ambulatory BP remained at ≥135/85 mm Hg (n=136) were randomized 1:1 to receive either an ultrasound-based RDN or a sham procedure.

The current results align with other sham-controlled trials with more optimized designs. [J Am Coll Cardiol 2019;73:1633-1642] The current findings also support those of RADIANCE-HTN SOLO, the other RADIANCE-HTN cohort which looked into a patient population with mild-to-moderate hypertension who were weaned off medications. [Lancet 2018;391:2335-2345]

Taken together, the findings suggest that catheter-based RDN via ultrasound or radiofrequency reduces BP across a spectrum of hypertension severity, noted Kirtane and colleagues. “If the BP-lowering effect and safety of RDN are maintained in the long-term … RDN offers an additional tool that we could use to help these patients, hopefully achieving better overall control of hypertension, especially if longer-term data support the durability and safety of the procedure.”

The team will continue to follow the participants for 3 years to ascertain the durability, safety, and long-term benefit of RDN for the different degrees of hypertension. The 6- and 12-month follow-up phases (masked and unmasked, respectively), wherein spironolactone is added as fourth-line therapy, will also explore whether RDN may be an alternative to adding other antihypertensives to reduce the risk of drug-related AEs and nonadherence to treatment. [Hypertension 2018;72:e53-e90]