Study Suggests Renal Denervation No More Effective Than Intensified Drug Treatment

In patients with true resistant hypertension, renal denervation does not result in a blood pressure drop greater than what can be achieved by intensified drug treatment including spironolactone, according to results of a prematurely halted randomized trial published online November 24, 2014, ahead of print in Hypertension. The procedure was, however, shown to be safe.

“Further studies on a larger sample of subjects with true [resistant hypertension] would be appropriate before the final role of denervation is established,” write Ján Rosa, MD, PhD, of General University Hospital (Prague, Czech Republic), and colleagues. “Currently, renal denervation is not a routine therapeutic approach in patients with severe hypertension and should be reserved for use only in hypertension centers and only after a thorough examination.”

Performed at 3 tertiary, high-volume centers in the Czech Republic, the PRAGUE-15 trial randomized patients with resistant hypertension—defined by an office systolic blood pressure > 140 mm Hg after treatment with at least 3 antihypertensives, including a diuretic—to renal denervation with the Symplicity catheter (Medtronic) or intensified pharmacotherapy that included spironolactone 25 mg daily in patients able to tolerate the drug. Resistant hypertension was confirmed with exclusion of secondary hypertension, 24-hour ambulatory blood pressure monitoring, and measurement of plasma antihypertensive drug levels before enrollment.

Following the release of SYMPLICITY HTN-3 results, the trial was stopped early after enrolling 52 patients in the renal denervation arm and 54 patients in the pharmacotherapy arm. Mean office blood pressure at baseline was 159/92 mm Hg and 155/89 mm Hg, respectively, in the 2 groups. Patients were taking an average of 5.1 and 5.4 antihypertensive drugs.

After 6 months, 24-hour systolic pressure declined in the renal denervation arm (by 8.6 mm Hg) and pharmacotherapy arm (by 8.1 mm Hg; both P = .001), but the reductions were similar between the groups (P = .87). The same pattern was seen for office systolic pressure as well as for diastolic pressure in both ambulatory and office settings.

After 6 months, the average number of drugs taken in the pharmacotherapy group rose by 0.3 (P < .001) reflecting increased use of spironolactone—although 21 patients could not take the medication because of hyperkalemia or intolerance. There was no change in the number of drugs used in the renal denervation arm.

After adjustment for the number of medications taken and aldosterone antagonist use, however, there was still no difference between the study arms in blood pressure changes during follow-up.

Patients receiving intensified pharmacotherapy had an increase in serum creatinine (5.3 µmol/L) and a decrease in creatinine clearance (-.3 mL/s per 1.73 m2; both P = .048), although the between-group comparisons were only borderline significant (P = .06). Six patients in this group developed hyperkalemia, and 1 developed unstable angina.

There were few side effects in the renal denervation group. One patient had an ischemic stroke, 1 an NSTEMI, and 1 a renal artery dissection that was treated with immediate stenting. All 4 spasms that occurred were managed with intraarterial nitrates.

Insights Into Both Strategies

Dr. Rosa and colleagues acknowledge that the study was limited by the lack of a sham control—as was used in SYMPLICITY HTN-3—and by the small number of patients, but they say that PRAGUE-15 had some advantages over the larger trial. Secondary causes of hypertension were thoroughly excluded and compliance with antihypertensive therapies was confirmed before enrollment, thus insuring the inclusion of true resistant hypertension patients, they say.

In an accompanying editorial, Felix Mahfoud, MD, of Saarland University Hospital (Homburg, Germany), and colleagues note that “the study provides interesting insights into the efficacy and safety of intensified drug treatment and catheter-based renal denervation in patients with resistant hypertension.”

They point out that most of the blood pressure reduction in the pharmacotherapy arm came from those who were able to take spironolactone, although the drug carries side effects that might not be fully apparent in the first 6 months.

The editorialists also question the researchers’ use of intention-to-treat analysis, calling it “objectionable in face of a relatively small number of patients and the obvious pilot character of the study because of its premature stop.” They add that “[p]er-protocol analyses with exclusion of patients receiving suboptimal treatment could have provided interesting insights.”

Yet according to Dr. Mahfoud and colleagues, the study raises important clinical questions:

If renal denervation is as effective as intensifying drug therapy, should patients get to choose which treatment they receive?

Should renal denervation be offered to patients who either do not want to start taking spironolactone or are at risk for side effects from the drug?

Is renal denervation a valid option for patients who do not respond to spironolactone?

“It will require additional rigorously performed, randomized, controlled clinical studies to determine the role of renal denervation in hypertension treatment finally, with or without spironolactone,” they conclude.

 


Sources:

 

1. Rosa J, Widimský P, Toušek P, et al. Randomized comparison of renal denervation versus intensified pharmacotherapy including spironolactone in true-resistant hypertension: six-month results from the PRAGUE-15 study. Hypertension. 2014;Epub ahead of print.

2. Mahfoud F, Ruilope LM, Böhm M, Schmieder RE. Aldosterone antagonists and renal denervation: friends or foes [editorial]? Hypertension 2014;Epub ahead of print.

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Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

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Disclosures
  • The study was supported by a research project from the Ministry of Education of the Czech Republic and by Charles University research project UNCE and PRVOUK.
  • Dr. Rosa reports no relevant conflicts of interest.
  • Dr. Mahfoud reports having support from Deutsche Hochdruckliga und Deutsche Gesellschaft für Kardiologie and receiving research grants, speaker honoraria, and consulting fees from Boston Scientific, Cordis, Medtronic/Ardian, and St. Jude.

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