麻豆传媒

Real but modest blood pressure reductions were achieved with renal denervation across six sham-controlled trials, a meta-analysis found.

Renal denervation cut 24-hour ambulatory systolic blood pressure by 3.65 mm Hg more than controls on average over a median follow-up of 2 to 6 months (P<0.001), reported Herbert Aronow, MD, MPH, of Warren Alpert Medical School of Brown University in Providence, Rhode Island, and colleagues in the .

"I think that the results should lead practitioners to keep their minds open about the possibility that this may in the end be a very effective strategy to help control blood pressure," Aronow told 麻豆传媒.

His group noted that the degree of blood pressure lowering "is in line with that observed in placebo-controlled trials of clinically effective antihypertensive drugs and approximates that deemed clinically meaningful by expert consensus."

These data "are interesting, although numerous questions arise regarding the future of RSD [renal sympathetic denervation] in the treatment of hypertension," wrote Sverre E. Kjeldsen, MD, PHD, of the University of Oslo in Norway, and colleagues in .

In December 2018, an FDA advisory committee met with stakeholders and manufacturers to discuss effectiveness endpoints, safety, potential indications, and other considerations for renal denervation and other as-yet-unapproved catheter-based treatments for high blood pressure.

Even as these details are sorted out, the evidence is clear that there is an antihypertensive effect of RSD, the editorialists wrote. "This conclusion is consistent with the known contribution of sympathetic overactivity in the pathogenesis of essential hypertension."

The latest trials have found that the procedure does really reduce blood pressure: RADIANCE-HTN SOLO and SPYRAL HTN-OFF MED both produced modestly positive data for denervation with newer-generation technology.

Indeed, the meta-analysis showed bigger reductions in daytime ambulatory systolic blood pressure with renal denervation in second-generation trials (6.12 vs 2.14 mm Hg for first-generation trials; P=0.04 for interaction). The interaction was not significant when it came to 24-hour monitoring, however.

"Although our study demonstrated more pronounced blood pressure reduction in second-generation trials for daytime ASBP [ambulatory systolic blood pressure], future studies will need to further examine whether second-generation is superior to first-generation trial design with respect to other blood pressure measurements," the study authors cautioned.

The first-generation trials "should be ignored," since the second-generation trials are "much more valid and more meaningful," commented John Hirshfeld Jr., MD, of the Hospital of the University of Pennsylvania in Philadelphia.

For their meta-analysis, the researchers included six randomized controlled trials that compared sham and renal denervation in at least 50 patients with uncontrolled hypertension. In all, there were 977 patients, with mean age ranging from 52.8 years to 64.5 years.

The investigators found that renal denervation was linked with blood pressure improvements over sham by a range of measures:

• Office diastolic blood pressure (weighted mean difference -3.37 mm Hg; P<0.001)
• Daytime ambulatory diastolic blood pressure (-1.57 mm Hg; P=0.008)
• 24-hour ambulatory diastolic blood pressure (-1.71 mm Hg; P=0.01)
• Office systolic blood pressure (-5.53 mm Hg; P<0.001)
• Daytime ambulatory systolic blood pressure (-4.07 mm Hg; P<0.001)

Adverse events related to renal denervation were rare. In the SYMPLICITY HTN-3 trial, major adverse events were found in 0.6% of the sham-controlled group and 1.4% of the renal denervation group.

The investigators acknowledged the limitations of their meta-analysis in that it pooled patients with varied characteristics from trials with different protocols. The trials involved short-term follow-up (max 6 months), were not powered to determine efficacy endpoints, and were designed for proof of concept.

"Some of the earlier trials enrolled a wide variety of patients, perhaps too broad of a patient group, allowed operators without much experience with the technique to perform the procedures, allowed for a lot of changes in medication to occur with patients throughout the duration of the trial, and chose an outcome in the trial that might not have been the ideal outcome to study, meaning the office blood pressure," said Aronow.

The findings of this analysis should inform the design of pivotal, larger trials to assess the long-term safety and efficacy of renal denervation among hypertension patients, the investigators said.