Renal Denervation for HTN: More Studies Needed

Renal denervation effected significant—but modest—reductions in both ambulatory and office blood pressure measurements, with an average reduction of about 4/2 mmHg, according to results of a meta-analysis published in the Journal of the American College of Cardiology. Further, this benefit was not affected by the use of antihypertensive treatments.

Researchers concluded, therefore, that renal denervation—a minimally invasive procedure that is still investigational in the U.S.—may be a viable option in patients with insufficiently treated hypertension who are not willing to add antihypertensive agents.

“Sham controlled trials have demonstrated that current renal denervation catheters produce a statistically significant reduction in blood pressure, albeit with a modest treatment size,” study co-author Deepak Bhatt, MD, MPH, executive director of Interventional Cardiovascular Programs, Brigham and Women’s Hospital Heart & Vascular Center, and professor of medicine, Harvard Medical School, Boston, told BreakingMED in an e-mail correspondence. “The mechanisms of action of renal denervation would be expected to provide a benefit in both types of patients. If approved, it would seem more logical to use it in patients who are maximally treated with medical therapy but still have poorly controlled blood pressure.”

For this meta-analysis, Bhatt and colleagues identified seven blinded, randomized, placebo-controlled trials of catheter-based renal denervation that compared its effects in patients treated with antihypertensive medications as well as those not treated.

In the 1,368 patients included in these trials (782 randomized to renal denervation; 586 to placebo), denervation significantly reduced the following blood pressure measurements:

• Ambulatory systolic: mean difference, −3.61 mmHg (95% CI: −4.89 to −2.33 mmHg; P˂0.0001).
• Ambulatory diastolic: mean difference, −1.85 mmHg (95% CI: −2.78 to −0.92; P˂0.0001).
• Office systolic: mean difference, −5.86 mmHg (95% CI: −7.77 to −3.94; P˂0.0001).
• Office diastolic: mean difference, −3.63 mmHg (95% CI: −4.77 to −2.50; P˂0.0001).

Bhatt and fellow researchers found no evidence of any significant impact of concomitant treatment with antihypertensive medications on effects of denervation at any endpoint.

Across seven trials, the following occurred: four deaths, nine strokes, one embolism, and two vascular complications, one case of new renal artery stenosis. But, noted researchers, adverse events “were rare and not more common with denervation than with the placebo procedure.”

According to Bhatt, more studies are needed.

“I think more data from randomized, sham-controlled trials are necessary. Longer term data and assessment of any impact on clinical events such as stroke and heart failure would be useful, though I am not aware of any such adequately powered, randomized, sham-controlled trials,” he said, adding that studies on the cost-efficacy of the procedure are also needed.

Ultimately, he told BreakingMED, “There is a potential role in patients with very poorly controlled blood pressure, such as patients already on multiple medications with intolerance to additional medications.”

David E. Kandzari, MD, of Piedmont Heart Institute, Atlanta, reviewed the trajectory of renal denervation.

“Over the past decade, renal denervation (RDN) has traveled a storied path from initial widespread enthusiasm poised for substantial public health impact only to be followed by abrupt disillusionment with lack of demonstrable efficacy in the SYMPLICITY HTN-3 trial. With perseverance, additional exploratory preclinical and clinical studies endeavored to show signals of effectiveness with RDN, and a contemporary generation of trials has consistently demonstrated safety and effectiveness. At present, five sham-controlled, randomized RDN studies using two different RDN methods have demonstrated significant BP reductions both in the presence and absence of concomitant antihypertensive therapies (Figure). Such studies not only reaffirm the biologic proof of principle for this novel treatment but also demonstrate a complementary benefit in uncontrolled hypertension despite prescribed medications,” he wrote in his accompanying editorial comment.

Kandzari added that, to date, there have been over 20 meta-analyses of studies of renal denervation published, with an almost equal number of reviews on its other effects.

“Given the promise of RDN and its potential to influence the escalating prevalence of uncontrolled hypertension, not only will there remain intense interest to individual clinical trial outcomes but also meta-analyses of aggregated results. Considering the cadence of studies in this space, the shelf-life of RDN meta-analyses is seemingly brief as the inclusion of each additional trial leads to a new report. As with other meta-analyses, interpretation will invariably assume a class effect to specific RDN technologies, similarity in enrollment criteria and patients, and equipoise among first generation versus more contemporary trials. Expectedly, the popularity of RDN meta-analyses will continue, yet the fairest of all will be considerate interpretation of the individual trials,” he concluded.

In an interview with BreakingMED, Dipti Itchhaporia, MD, president of the American College of Cardiology, noted that this analysis was underpowered and did not demonstrate durability of results.

She succinctly summed up the results from Bhatt et al.

“Until now, we have not seen any significant difference in the past in the trials. In previous sham trials, there was no benefit. But here, there seems to be a small signal, and what this tells us is that there needs to be a larger trial to see if this is really a trend,” she said.

“Before, the door was sort of closed on renal denervation. Maybe there’s a little bit of an opening—a crack—to say that there may be some benefit. But I don’t know if we can say that with this underpowered study. We need a larger trial to really [be able to] say that,” Itchhaporia concluded.

Study limitations include the short duration of follow-up, that the analysis was limited to the effects of denervation on only BP rather than on events, differing study variables and antihypertensive regimens used in the trials, and the inclusion of only randomized, blinded, placebo-controlled trials.

1. Renal denervation led to modest but significant reductions in all ambulatory and office BP parameters, according to a systematic review and meta-analysis of seven blinded placebo-controlled randomized trials.

2. Researchers and experts caution that larger scale observational studies are needed to assess safety and long-term durability of results.

Liz Meszaros, Deputy Managing Editor, BreakingMED™

Cat ID: 6

Topic ID: 74,6,730,6,127,410,192,916