Medicine uptitration amps up RDN benefit for drug-resistant hypertension

In patients with multidrug-resistant hypertension (HTN), the blood pressure (BP)-lowering benefit of renal denervation (RDN) achieved at 2 months was amplified when a stepped-care medication escalation protocol was added between 2 and 6 months, updates from the RADIANCE-HTN TRIO trial have shown.

“At 2 months, there were greater reductions with RDN vs a sham procedure, on the background of the combination triple* pill,” said Dr Ajay Kirtane from Columbia University Irving Medical Center, New York City, New York, US, during his virtual presentation at TCT 2021.

“In the 6-month analysis … further BP reductions were observed in both arms [when] we sought to evaluate the effects of [medicine uptitration] if home BP remained uncontrolled from 2 to 6 months after randomization,” Kirtane continued. “[T]he RDN arm started off ahead at 1 and 2 months, particularly home systolic BP (SBP), and remained ahead out to 6 months.”

After adjusting for baseline BP and number of medications, the drop in home SBP remained significant in favour of RDN vs sham (mean, –11.5 vs –8.9 mm Hg; p=0.027). The difference was not significant for office (mean, –10.4 vs –11.2 mm Hg; p=0.240) and daytime ambulatory SBP (mean, –11.8 vs –12.3 mm Hg; p=0.65). [TCT 2021, Late-Breaking Clinical Science Session]

There was a slight increase in additional medications used at 6 months in both the RDN and sham arms (0.7 vs 1.1; p=0.045). Use of aldosterone antagonists also increased, but to a lesser extent in the RDN vs the sham arm (40 percent vs 61 percent; p=0.017).

“As far as safety data goes, there was not really a change between baseline and 6 months and no difference between study arms with regard to eGFR**,” noted Kirtane.

 

RDN an additional option, NOT a replacement

A total of 136 patients were initially randomized 1:1 to receive either the RDN or a sham procedure for 2 months. Patients who still had elevated BPs after 2 months (n=130) received an additional regimen comprising spironolactone 25 mg, sequentially followed by bisoprolol 10 mg, a centrally acting α2 receptor agonist***, and an α1 receptor blocker^#.

“It is important to put the results into clinical perspective,” Kirtane noted. “[W]e have to emphasize that lifestyle modification and pharmacotherapy, especially as shown in this trial, are effective and standard of care for treating HTN. It is notable that the sham arm had further and dramatic reductions in BP with the initiation of an aldosterone antagonist; therefore, we know lifestyle modification and pharmacotherapy worked.”

However, despite best efforts to institute these interventions, nonadherence and intolerance may occur, leading to persistently elevated BP and resistant HTN, thus increasing cardiovascular disease risk over time, he continued. “[T]herefore, the question is, what is the role of RDN in that background?”

“In that light, RDN can offer an additional – but not a replacement – option to further lower BP, especially for patients whose BP is uncontrolled despite genuine attempts to institute conventional therapies,” Kirtane concluded.

 

Important additional evidence

“These data are really important, because [these add to] our knowledge that RDN works [not only] in patients without any anti-HTN medications but also in patients on a triple fixed combination, and now in patients [receiving] fourth-line anti-HTN drugs,” commented virtual discussant Dr Felix Mahfoud from the Saarland University Hospital, Homburg, Germany.

Presenter Dr David Kandzari from Piedmont Healthcare, Atlanta, Georgia, US, added his insights. “This is a welcome addition to the breadth of evidence we have emerging with RDN. It shows some sustainability albeit through 6 months with it. It again highlights safety, which is a consistent message.”

“[Moreover,] medication burden is a large driver in terms of patient preferences for a device-based vs a pharmacologic approach. In most instances, these are going to be complimentary therapies like it is for just about all interventions that we do, but the impact on medication burden I think will be quite meaningful,” added Kandzari.