Modest, mixed BP benefits seen with alcohol-mediated renal denervation: TARGET BP-1
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Key takeaways:
- Alcohol-mediated renal nerve denervation is a novel strategy for people with uncontrolled and treatment-resistant hypertension.
- There was a large placebo effect seen in the sham group.
ATLANTA — Adults with uncontrolled and treatment-resistant hypertension saw a modest reduction in 24-hour ambulatory BP with alcohol-mediated renal nerve denervation, although other mixed findings complicate the picture, researchers reported.
The TARGET BP-1 trial, presented at the American College of Cardiology Scientific Session, also showed no significant differences in office BP measures at 3 months between patients who underwent renal denervation or a sham procedure, as well as unexpectedly large BP reductions observed in the sham control group that researchers could not explain.
“In a large, international, sham-controlled randomized trial, alcohol-mediated renal denervation achieved its primary endpoint, with a significant reduction in 24-hour ambulatory BP, but the BP reduction is modest, and we see directionally greater reductions in other measures of BP, although they do not achieve statistical significance,” David E. Kandzari, MD, director of interventional cardiology and chief of the Piedmont Heart Institute and Cardiovascular Service Line in Atlanta, told Healio. “There was an exceptionally large [BP] reduction in the sham control group that, right now, is not fully explainable by testing and current findings. The study was also challenged by the highest rates of medical nonadherence by protocol mandate that we have ever seen in renal denervation trials.”
Need for more therapy options
Globally, more than one-third of adults have hypertension yet many remain uncontrolled, leading to an increased risk for CV events, Kandzari said during the late-breaking clinical trial presentation. A 5 mm Hg absolute reduction in office systolic BP can lead to a 10% reduction in major CV events, Kandzari said.
As Healio previously reported, the FDA recently approved two catheter renal denervation systems: one using ultrasound technology (Paradise, Recor Medical) and one using radiofrequency technology, both indicated for adults with uncontrolled hypertension. Catheter-based perivascular delivery of dehydrated alcohol is a novel method of neural ablation and has the ability to achieve a confluent arc of ablation with a single, targeted treatment in the renal artery.
“As of now, we do not have an identifiable marker for the completeness of denervation, so there may be alternative technologies, such as alcohol-mediated denervation, that may be more effective with greater efficiency,” Kandzari told Healio.
For TARGET BP-1, researchers analyzed data from 301 adults in nine countries with an office systolic BP of 150 to 180 mm Hg, office diastolic BP of 90 mm Hg or higher and mean 24-hour ambulatory systolic BP of 135 to 170 mm Hg, all despite prescription for two to five antihypertensive medications, including diuretic therapy.
“These were fairly hypertensive patients despite treatment,” Kandzari told Healio. “The office BPs approached a mean of 164/99 mm Hg; the 24-hour ambulatory BP was approximately 146/88 mm Hg.”
The primary endpoint was baseline-adjusted change in mean 24-hour ambulatory systolic BP at 3 months. Secondary endpoints included mean between-group differences in office and ambulatory BP at additional time points. Researchers also performed blood and urine testing to assess adherence to BP medications.
The findings were simultaneously published in Circulation.
Large BP reduction in sham controls
Compared with sham controls, renal denervation with the Peregrine System Kit (Ablative Solutions) was associated with a significant reduction in 24-hour ambulatory systolic BP at 3 months, with mean absolute reductions of –10 mm Hg vs. –6.8 mm Hg, respectively, for a treatment difference of –3.2 mmHg (95% CI, –6.3 to 0; P = .0487).
“This reduction with renal denervation was very impactful, but conversely, there was a 6.8 mm Hg reduction in the sham control group that perhaps lessened the potential difference between the two groups,” Kandzari told Healio.
In subgroup analysis of the primary endpoint, there were no interactions across predefined subgroups.
At 3 months, the mean change in office systolic BP was –12.7 mm Hg and –9.7 mm Hg for renal denervation and sham, respectively, for a treatment difference of –3 mm Hg (95% CI, –7 to 1; P = .173). There were no significant differences in ambulatory or office diastolic BP.
Kandzari noted that nonadherence to BP medications during the study was particularly high and occurred at rates not seen in other sham-controlled renal denervation trials, further complicating findings.
“Although, per protocol, medication changes were prohibited from baseline to follow up ... when we evaluated urine and blood testing for drug adherence at baseline, [nonadherence] approached nearly 60% at baseline and 50% at 3-month follow-up,” Kandzari told Healio. “It did not significantly differ between the two groups, but these findings are against the backdrop of very high nonadherence. This is one of the reasons why renal denervation has come to the forefront, due to having an ‘always on’ [antihypertensive] effect.”
At 6 months, adverse safety events were uncommon, with one instance of accessory renal artery dissection in the renal denervation group (0.7%).
“The therapy proves to be very safe, but with regards to efficacy, it is going to be a waiting game to see whether there is a sustained BP reduction in the renal denervation group and a loss of BP control in the sham patients,” Kandzari told Healio.
Reference:
Perspective
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Keith C. Ferdinand, MD, FACC, FAHA, FASPC, FNLA
The FDA recently approved two tools for renal nerve denervation, using ultrasound and radiofrequency. TARGET BP-1 uses a novel approach, ethanol, to denervate the renal arteries. This study was relatively small, with just 301 patients. Although the systolic BP lowering was marginal ,we look forward to data with perhaps a larger sample size and more rigorous BP lowering.
One thing that was a little surprising is that one of the promises of renal denervation is the ability to lower nocturnal BP. In the subanalysis of BP during the nighttime, there was no significant lowering. This again suggests that we need more data on this particular approach. However, we look forward to this tool as it develops, since now we have at least two forms of renal denervation. If this method is successful, in the future, we may have three.
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Wanpen Vongpatanasin, MD, FAHA
Congratulations to Dr. Kandzari and his study team. The magnitude of reduction in BP when compared with the sham group was around 3 mm Hg at short-term, 3-month follow up — a modest effect on BP.
It is important to note that this study included a select group of adults with hypertension: those with systolic BP between 150 mm Hg and 180 mm Hg, a mean diastolic BP of 90 mm Hg and prescribed two to five antihypertensive medications, including treatment with at least one diuretic. There were also many exclusion criteria for participants, such as kidney disease with [estimated glomerular filtration rate] of 45 mL/min/1.73 m2 or less, recent MI, unstable angina, stroke and obstructive sleep apnea, which is present in 20% to 50% of people with hypertension.
The rate of approximately 50% nonadherence observed in this study is consistent with most studies in the literature and not surprising. Unfortunately, a 3 mm Hg reduction in BP will not provide much meaningful benefit for patients with the baseline BP criteria for this study. This is important considering participants were not able to reduce number or dosage of antihypertensive medication for these patients.
For people with hypertension, shared decision-making is key. We need more research to see if better results may be achievable if we denervate the sympathetic nerve in organs such as the mesenteric nerve that also contributes to BP control. The rising national and global burden of hypertension creates urgency for us to explore new ways to help patients achieve better BP control.
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