Renal Denervation May Lower Treatment Burden, as Well as Blood Pressure: RADIANCE-HTN SOLO

(UPDATED) Patients with hypertension undergoing ultrasound-based renal denervation (Paradise; ReCor Medical) had sustained reductions in systolic blood pressure—and were prescribed fewer antihypertensive medications—when compared with patients who underwent a sham procedure, according to new data from the RADIANCE-HTN SOLO study.

The results, which were presented at the American College of Cardiology 2019 Scientific Session and published in Circulation, suggest that if the safety of renal denervation is maintained long term, the endovascular procedure could be a promising adjunctive therapy for patients with hypertension.

“Everybody remembers SYMPLICITY HTN-3 being a negative study, and there were many reasons why we think that was the case,” senior investigator Ajay Kirtane, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), told TCTMD. “Some of that had to do with the technique and the device, and some of it also had to do with study design. In many ways, it wasn’t designed badly, but I don’t think people realized how many medication changes patients would have in the background of the study. . . . It becomes very difficult then to asses the effect of a therapy like renal denervation when medicines are changing up and down.”   

Since SYMPLICITY HTN- 3, the field has started to bounce back, although it’s a cautious enthusiasm that reigns today. Several randomized, sham-controlled studies have demonstrated positive results, including SPYRAL HTN-OFF MED, SPYRAL HTN-ON MED, and RADIANCE-HTN SOLO. The REDUCE HTN: REINFORCE study, however, could not duplicate that success.

Sripal Bangalore, MD (NYU Langone Medical Center, New York, NY), who has been critical of the field’s exuberance in the past, particularly the early excitement around the massive reductions in systolic blood pressure seen in the single-arm studies, said these sham-controlled randomized trials have moved the field forward by showing renal denervation effectively lowers blood pressure when the confounding effect of antihypertensive therapy is removed.

“For me, we need more definitive trials, which are already in the works, but if those trials show the same result—that renal denervation reduces blood pressure—I would think there are several groups of patients where it might be beneficial,” Bangalore told TCTMD. “I’m very optimistic that this will have a role in the future,” he said. 

Similarly, Anuradha Tunuguntla, MD (Nebraska Heart Institute, Lincoln), who chaired the session at the ACC meeting, told TCTMD that RADIANCE-HTN SOLO, as well as some of the other trials, have helped physicians and researchers come to a better understanding of ultrasound-based renal denervation. “We can now say with certainty that it is effective at lowering blood pressure through a simple, straightforward procedure without much risk,” she said. “Having the sham-control is the most important key, especially in a setting like hypertension where there is a placebo effect.”  

Can Renal Denervation Reduce Medication Burden?

The 2-month results of the 140-patient RADIANCE-HTN SOLO study, which were presented at EuroPCR in May 2018, showed that renal denervation reduced daytime ambulatory blood pressure in the absence of medication. As reported by TCTMD, renal denervation in hypertensive patients not currently taking medical therapy reduced systolic blood pressure by 8.5 mm Hg versus 2.2 mm Hg in the sham-control arm, a between-group difference of 6.3 mm Hg. 

As part of the trial, patients remained off medication for 2 months after the intervention/sham unless they exceeded safety blood pressure criteria. Between 2 and 5 months, physicians stepped up antihypertensive treatment if the monthly measured home blood pressure was 135/85 mm Hg or greater. Treatment included the sequential addition of amlodipine 5 mg, standard-dose ACE inhibitor, and hydrochlorothiazide 12.5 mg, followed by dose increases of amlodipine and hydrochlorothiazide as needed.

“Renal denervation is probably not going to be a substitute for medication,” said Kirtane. “The question is: can it reduce the medication burden? In the construct of patients coming off their medication, you get a ‘reset’ in a sense. After the procedure, or the sham procedure, you add back medication to see how many medicines are needed to control their blood pressure. One of the cool aspects of this study is that patients were still blinded so we’re [adding medicine] and the treatment team doesn’t know if the patient has had the procedure or the sham. It’s a blinded test of what is required to get patients to control.”

At 6 months, 65.2% of patients in the renal denervation arm were receiving antihypertensive medication compared with 84.5% of those in the sham-control arm (P = 0.008). Patients in the intervention arm were taking, on average, 0.9 medications, versus 1.3 in the sham group. Overall, 34.8%, 42.0%, and 17.4% of patients undergoing renal denervation were taking zero, 1, or 2 medications at 6 months, respectively. In contrast, 15.5%, 47.9%, or 26.8% of patients in the sham arm were taking the same number of antihypertensive medications at 6 months. The defined daily dose of antihypertensive medications was also significantly lower in the renal denervation arm.

Despite the less intensive use of medical therapy, renal denervation reduced daytime ambulatory systolic blood pressure to a greater extent: 18.1 mm Hg with renal denervation versus 15.6 mm Hg in the control arm (adjusted between-group difference 4.3 mm Hg; P = 0.024). In the present study, there were no major adverse events at 6 months in either group.  

Bangalore noted that a 4-mm Hg difference in ambulatory blood pressure is equivalent to an approximate 10-mm Hg reduction in office blood pressure, although the between-group difference accounts for changes in medication between 2 and 5 months.  “If you step back, and look at the 2-month results, which was a 6-mm Hg decrease, what does that mean? Depending on the agent you use, it could be half a hypertensive agent, or a full hypertensive agent. It’s a decent amount, but it’s not what we saw back in the day. Some of those early SYMPLICITY studies showed a 30-mm Hg decrease. We’re not seeing that. It’s more realistic now.”

Kirtane said eliminating a full hypertensive medication from daily use would be “clinically meaningful for patients.” Patients with more severe hypertension, such as those refractory to treatment, are likely to see the biggest antihypertensive effect with renal denervation, he added.

Blood Pressure is Hard to Control    

While renal denervation is likely to be an adjunctive therapy, or an alternative to the escalation of antihypertensive medications, Kirtane pointed out there are patients who achieve adequate control of their blood pressure without the addition of drugs. However, even within this randomized, clinical trial, just 56.5% and 43.7% in the renal denervation and sham arms, respectively, had ambulatory systolic blood pressures under control (defined as < 135 mm Hg).

“It shows us blood pressure is hard to control, number one, and number two, that in the real world the rate of control is probably a lot worse,” he said. As a clinician, any blood pressure-lowering tool, “particularly one you don’t have to take every day, has the potential to be helpful provided we can further prove its long-term safety and efficacy,” said Kirtane.

For Bangalore, while treatment-resistant hypertensive patients would be obvious candidates for renal denervation, patients taking a large number of medications for concurrent conditions could also be considered.

“If you want to reduce treatment burden, where we’re reducing the number of pills, maybe it’s a group of patients to consider?” said Bangalore. “The third group would be patients enrolled in these trials—simple hypertensive patients washed off [treatment]. To me, this trial showed that one in three patients who got the procedure were free of blood pressure medication at 6 months. I don’t think that’s trivial.”

To TCTMD, Tunuguntla said that compliance is a major issue for some patients, particularly those who are taking multiple medications, or taking high doses of drugs. Being able to reduce medication burden can reduce the potential for side effects or drug-drug interactions, especially in higher-risk patients with comorbid conditions, she said. Tunuguntla agreed that renal denervation would likely play a role in treatment-resistant hypertension, and that it could also emerge as a treatment in younger, low-risk patients with mild-to-moderate hypertension.

“A lot of them don’t want to be on a daily medication,” she said. “I see a lot of patients and there is a lot of hesitation.” When the topic of starting drug therapy comes up in conversation, patients suddenly want to try almost anything first before committing to antihypertensive medication, she noted. “It’s unique in that we have a procedure for a long-term condition that can be treated without compliance issues of taking medication every day.”  

Kirtane, Bangalore, and Tunuguntla all stressed that long-term studies are still needed to assess safety, as well as the durability of the blood pressure effect (RADIANCE-HTN SOLO is scheduled to follow patients for 3 years).