Raymond R Townsend, Felix Mahfoud, David E Kandzari, Kazuomi Kario, Stuart Pocock, Michael A Weber, Sebastian Ewen, Konstantinos Tsioufis, Dimitrios Tousoulis, Andrew S P Sharp, Anthony F Watkinson, Roland E Schmieder, Axel Schmid, James W Choi, Cara East, Anthony Walton, Ingrid Hopper, Debbie L Cohen, Robert Wilensky, David P Lee, Adrian Ma, Chandan M Devireddy, Janice P Lea, Philipp C Lurz, Karl Fengler, Justin Davies, Neil Chapman, Sidney A Cohen, Vanessa DeBruin, Martin Fahy, Denise E Jones, Martin Rothman, Michael Böhm, SPYRAL HTN-OFF MED trial investigators*, Jiro Aoki, Bryan Batson, Michael Böhm, James W Choi, Debbie L Cohen, George Dangas, Shukri David, Justin Davies, Chandan M Devireddy, David Kandzari, Kazuomi Kario, David P Lee, Philipp C Lurz, Manesh Patel, Kiritkumar Patel, Roland E Schmieder, Andrew S P Sharp, Jasvindar Singh, Konstantinos Tsioufis, Anthony Walton, Thomas Weber, Joachim Weil, Thomas Zeller, Khaled Ziada, Kengo Tanabe, Robert Wilkins, Felix Mahfoud, Cara East, Robert Wilensky, Johanna Contreras, Susan Steigerwalt, Neil Chapman, Janice P Lea, Denise Reedus, Satoshi Hoshide, Adrian Ma, Karl Fengler, Laura Svetkey, Anjani Rao, Axel Schmid, Anthony F Watkinson, Angela Brown, Dimitrios Tousoulis, Ingrid Hopper, Markus Suppan, Tolga Agdirlioglu, Elias Noory, Craig Chasen

Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; p<0·0001), office SBP -10·0 mm Hg (-15·1 to -4·9; p=0·0004), and office DBP -5·3 mm Hg (-7·8 to -2·7; p=0·0002). No significant changes were seen in the sham-control group: 24-h SBP -0·5 mm Hg (95% CI -3·9 to 2·9; p=0·7644), 24-h DBP -0·4 mm Hg (-2·2 to 1·4; p=0·6448), office SBP -2·3 mm Hg (-6·1 to 1·6; p=0·2381), and office DBP -0·3 mm Hg (-2·9 to 2·2; p=0·8052). The mean difference between the groups favoured renal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP -5·0 mm Hg (95% CI -9·9 to -0·2; p=0·0414), 24-h DBP -4·4 mm Hg (-7·2 to -1·6; p=0·0024), office SBP -7·7 mm Hg (-14·0 to -1·5; p=0·0155), and office DBP -4·9 mm Hg (-8·5 to -1·4; p=0·0077). Baseline-adjusted analyses showed similar findings. There were no major adverse events in either group. Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation. Medtronic.