Renal Denervation to Control Blood Pressure: Case Closed?

A study of renal denervation therapy may have been underpowered to detect important improvements in blood pressure control over a 6-month period.

The SIMPLICITY HTN-3 trial investigated the role of renal denervation as a new treatment modality for patients with medication-resistant hypertension. In this trial, which was conducted across 87 study centers in the United States, 535 patients with medication-resistant hypertension either received the denervation procedure or a sham procedure, in addition to usual care with antihypertensive medication.

During the Simplicity procedure, the physician uses a catheter to alter the output of nerves that are present in the renal artery. These nerves lead to the kidneys, contributing to the sympathetic nervous system activation that modulates the kidneys’ long-term control of blood pressure. By reducing the sympathetic output of the nerves to the kidneys, the procedure may improve blood pressure control.

Approximately two-thirds of patients in the trial received the procedure, and the remaining one-third of patients underwent a sham surgery. The results, announced at the 63th Scientific Meeting of the American Cardiology College in Washington, DC, March 29-31, 2014, showed that the surgery failed to meet its primary end point of reducing blood pressure between the baseline and 6-month evaluation time. As a result, Medtronic has ceased further investigation—a business move that may not be justified, given the design of the SIMPLICITY HTN-3 trial.¹

Some clinicians believe that the SIMPLICITY HTN-3 trial was underpowered to detect a difference in the blood pressure levels between control groups and treatment groups. The SIMPLICITY HTN-3 trial was designed to detect a 15-mmHg difference between the sham and surgery groups. If, for instance, the actual difference achieved with renal denervation was 7 mmHg, the difference in blood pressure levels between the sham and control groups would show no significant difference in blood pressure readings.²

The results of the larger SIMPLICITY HTN-3 trial conflict with the results of the smaller, earlier SIMPLICITY HTN-2 trial. In a 24-month follow-up of patients enrolled in the SIMPLICITY HTN-2 trial, reported at the 62nd Annual Scientific Session of the American College of Cardiology, March 9-11, 2013, the procedure reduced systolic blood pressure by an average of 29 mmHg and reduced systolic blood pressure by an average of 10 mmHg in a group of 40 patients.³

Renal denervation therapy with Medtronic's Simplicity system is minimally invasive and the procedure has a low rate of adverse events.^1,3

Results of a larger analysis may be necessary to show the benefit that may be attained with use of the Simplicity system. Although the SIMPLICITY HTN-3 trial included a substantial number of patients (N = 535), the study may have been underpowered to detect decreases in blood pressure as large as 7 mmHg. If Medtronic decides to pursue approval of the Simplicity system, post hoc analyses may help the investigators identify subgroups of patients that may benefit from treatment with Medtronic’s renal denervation procedure.^1-3

References:

• Medtronic. Medtronic Announces U.S. Renal Denervation Pivotal Trial Fails to Meet Primary Efficacy Endpoint While Meeting Primary Safety Endpoint [press release]. http://newsroom.medtronic.com/phoenix.zhtml?c=251324&p=irol-newsArticle&ID=1889335. Accessed April 2014.
• Staessen JA, Jin Y, Persu A. SYMPLICITY HTN-3 results to be announced: a mystery or a story foretold? J Biomed Res. 2014;28(2):73-74.
• Medtronic. New Data Reinforce Significant Blood Pressure Reduction Sustained to Two Years Using the Symplicity Renal Denervation System [press release]. http://newsroom.medtronic.com/phoenix.zhtml?c=251324&p=irol-newsArticle&ID=1802677&highlight=. Accessed April 2014.