TY - JOUR
T1 - Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED)
T2 - a randomised, sham-controlled, proof-of-concept trial
AU - Townsend, Raymond R.
AU - Mahfoud, Felix
AU - Kandzari, David E.
AU - Kario, Kazuomi
AU - Pocock, Stuart
AU - Weber, Michael A.
AU - Ewen, Sebastian
AU - Tsioufis, Konstantinos
AU - Tousoulis, Dimitrios
AU - Sharp, Andrew S.P.
AU - Watkinson, Anthony F.
AU - Schmieder, Roland E.
AU - Schmid, Axel
AU - Choi, James W.
AU - East, Cara
AU - Walton, Anthony
AU - Hopper, Ingrid
AU - Cohen, Debbie L.
AU - Wilensky, Robert
AU - Lee, David P.
AU - Ma, Adrian
AU - Devireddy, Chandan M.
AU - Lea, Janice P.
AU - Lurz, Philipp C.
AU - Fengler, Karl
AU - Davies, Justin
AU - Chapman, Neil
AU - Cohen, Sidney A.
AU - DeBruin, Vanessa
AU - Fahy, Martin
AU - Jones, Denise E.
AU - Rothman, Martin
AU - Böhm, Michael
AU - Aoki, Jiro
AU - Batson, Bryan
AU - Dangas, George
AU - David, Shukri
AU - Patel, Manesh
AU - Patel, Kiritkumar
AU - Singh, Jasvindar
AU - Weber, Thomas
AU - Weil, Joachim
AU - Zeller, Thomas
AU - Ziada, Khaled
AU - Tanabe, Kengo
AU - Wilkins, Robert
AU - Contreras, Johanna
AU - Steigerwalt, Susan
AU - Reedus, Denise
AU - Hoshide, Satoshi
N1 - Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/11/11
Y1 - 2017/11/11
N2 - Background 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. Methods 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. Findings 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. Interpretation Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation. Funding Medtronic.
AB - Background 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. Methods 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. Findings 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. Interpretation Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation. Funding Medtronic.
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U2 - 10.1016/S0140-6736(17)32281-X
DO - 10.1016/S0140-6736(17)32281-X
M3 - Article
C2 - 28859944
AN - SCOPUS:85028396109
SN - 0140-6736
VL - 390
SP - 2160
EP - 2170
JO - The Lancet
JF - The Lancet
IS - 10108
ER -