Renal denervation and Symplicity HTN-3: "Dubium sapientiae initium" (doubt is the beginning of wisdom).

Abstract

Recently, results of the Simplicity Hypertension-3 (HTN-3)1 study have been presented at the American College of Cardiology scientific sessions and simultaneously published in the New England Journal of Medicine .1 Ever since the sponsoring company announced on January 9, 2014, that the study failed to meet its primary efficacy end point, the scientific community has been anxiously awaiting the details of this pivotal study. Now that the results are in and details are known (to some extent), it is time to examine the facts carefully, put the data into perspective, and deliberate on the future of renal denervation (RDN) as a therapeutic option. The study was the first randomized, single-blinded, sham-controlled study in the RDN literature. The study included 535 patients with drug-resistant hypertension randomly assigned to optimal medical therapy plus RDN or to optimal medical therapy alone plus sham procedure. The procedure was performed by >100 interventionalists throughout the United States. The study met its primary safety end point: a composite of all-cause mortality, end-stage renal disease, embolic events resulting in end-organ damage, any vascular complication, hypertensive crisis, or renal artery stenosis. The study, however, failed to meet its primary efficacy end point. Results indicate that there was no significant difference in blood pressure (BP) reduction either in the office or as measured by ambulatory monitoring. At 6 months, office BP decreased by 14.1±24 mm Hg in the RDN group and by 11.7±26 mm Hg in the sham control group ( P =0.255). The average 24-hour ambulatory systolic BP decreased by 6.75±15.11 mm Hg in the RDN group and by 4.79±17.25 mm Hg in the sham control group for a difference of 1.96 mm Hg ( P =0.979) for superiority with a margin of 2 mm Hg, thus missing the major secondary end point of the study. Although the …