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World J Hypertens. May 23, 2015; 5(2): 74-78
Published online May 23, 2015. doi: 10.5494/wjh.v5.i2.74
Symplicity-3 hypertension trial: Basic and clinical insights
Benjamin J Scherlag, Sunny S Po
Benjamin J Scherlag, Sunny S Po, Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States
Author contributions: Both authors contributed to this manuscript.
Conflict-of-interest: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Benjamin J Scherlag, PhD, Heart Rhythm Institute, University of Oklahoma Health Sciences Center, 1200 Everett Drive (6E103), Oklahoma City, OK 73104, United States. benjamin-scherlag@ouhsc.edu
Telephone: +1-405-2054457 Fax: +1-405-2717455
Received: September 27, 2014
Peer-review started: September 28, 2014
First decision: December 17, 2014
Revised: February 19, 2015
Accepted: March 16, 2015
Article in press: March 18, 2015
Published online: May 23, 2015
Abstract

Symplicity-3 hypertension (HTN) was a recently completed clinical trial that was assumed to be the basis for the approved use of renal artery denervation for the treatment of resistant hypertension in the United States. Dramatic reductions in blood pressure had been reported in two clinical trials (Symplicity-1HTN, -2HTN) carried out in Europe, however Symplicity-3HTN did not show a significant reduction of systolic blood pressure in patients with resistant hypertension 6 mo after renal artery denervation as compared with a sham control. (Denervation group, blood pressure reduction: -14 ± 24, Sham control: -12 ± 26 mmHg). In this review we discuss several potential explanations for the failure of efficacy of Symplicity-3HTN taking into account basic and clinical factors which could have played a role in the discrepancy between the European and American experience.

Keywords: Hypertension, Renal artery denervation, Aorticorenal ganglia, Atrial fibrillation

Core tip: The failure of the Symplicity-3 trial which subjected patients to renal artery denervation to significantly reduce resistant hypertension has been ascribed to many factors. In this review, we focus on the lack of a “biomarker” as a major deficiency in achieving the expected efficacy. We also present experimental and clinical evidence to support the importance of a biomarker to acutely predict long term success of renal artery denervation for effective treatment for drug resistant hypertension.