Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED)

A randomised, sham-controlled, proof-of-concept trial

Raymond R Townsend, Felix Mahfoud, David E Kandzari, Kazuomi Kario, Stuart J Pocock, Michael A. Weber, Sebastian Ewen, Konstantinos Tsioufis, Dimitrios Tousoulis, Andrew S.P. Sharp, Anthony F. Watkinson, Roland Erich Schmieder, Axel Schmid, James W. Choi, Cara East, Anthony Walton, Ingrid Hopper, Debbie L. Cohen, Robert Wilensky, David P. Lee & 13 others Adrian Ma, Chandan M Devireddy, Janice P Lea, Philipp C. Lurz, Karl Fengler, Justin Davies, Neil Chapman, Sidney A. Cohen, Vanessa DeBruin, Martin P Fahy, Denise E. Jones, Martin T Rothman, Michael Böhm

Research output: Contribution to journalArticleResearchpeer-review

204 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2160-2170
Number of pages11
JournalThe Lancet
Volume390
Issue number10108
DOIs
Publication statusPublished - 11 Nov 2017

Keywords

  • renal denervation
  • hypertension

Cite this

Townsend, Raymond R ; Mahfoud, Felix ; Kandzari, David E ; Kario, Kazuomi ; Pocock, Stuart J ; Weber, Michael A. ; Ewen, Sebastian ; Tsioufis, Konstantinos ; Tousoulis, Dimitrios ; Sharp, Andrew S.P. ; Watkinson, Anthony F. ; Schmieder, Roland Erich ; Schmid, Axel ; Choi, James W. ; East, Cara ; Walton, Anthony ; Hopper, Ingrid ; Cohen, Debbie L. ; Wilensky, Robert ; Lee, David P. ; Ma, Adrian ; Devireddy, Chandan M ; Lea, Janice P ; Lurz, Philipp C. ; Fengler, Karl ; Davies, Justin ; Chapman, Neil ; Cohen, Sidney A. ; DeBruin, Vanessa ; Fahy, Martin P ; Jones, Denise E. ; Rothman, Martin T ; Böhm, Michael. / Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED) : A randomised, sham-controlled, proof-of-concept trial. In: The Lancet. 2017 ; Vol. 390, No. 10108. pp. 2160-2170.
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title = "Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): A randomised, sham-controlled, proof-of-concept trial",
abstract = "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.",
keywords = "renal denervation, hypertension",
author = "Townsend, {Raymond R} and Felix Mahfoud and Kandzari, {David E} and Kazuomi Kario and Pocock, {Stuart J} and Weber, {Michael A.} and Sebastian Ewen and Konstantinos Tsioufis and Dimitrios Tousoulis and Sharp, {Andrew S.P.} and Watkinson, {Anthony F.} and Schmieder, {Roland Erich} and Axel Schmid and Choi, {James W.} and Cara East and Anthony Walton and Ingrid Hopper and Cohen, {Debbie L.} and Robert Wilensky and Lee, {David P.} and Adrian Ma and Devireddy, {Chandan M} and Lea, {Janice P} and Lurz, {Philipp C.} and Karl Fengler and Justin Davies and Neil Chapman and Cohen, {Sidney A.} and Vanessa DeBruin and Fahy, {Martin P} and Jones, {Denise E.} and Rothman, {Martin T} and Michael B{\"o}hm",
year = "2017",
month = "11",
day = "11",
doi = "10.1016/S0140-6736(17)32281-X",
language = "English",
volume = "390",
pages = "2160--2170",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier",
number = "10108",

}

Townsend, RR, Mahfoud, F, Kandzari, DE, Kario, K, Pocock, SJ, Weber, MA, Ewen, S, Tsioufis, K, Tousoulis, D, Sharp, ASP, Watkinson, AF, Schmieder, RE, Schmid, A, Choi, JW, East, C, Walton, A, Hopper, I, Cohen, DL, Wilensky, R, Lee, DP, Ma, A, Devireddy, CM, Lea, JP, Lurz, PC, Fengler, K, Davies, J, Chapman, N, Cohen, SA, DeBruin, V, Fahy, MP, Jones, DE, Rothman, MT & Böhm, M 2017, 'Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): A randomised, sham-controlled, proof-of-concept trial', The Lancet, vol. 390, no. 10108, pp. 2160-2170. https://doi.org/10.1016/S0140-6736(17)32281-X

Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED) : A randomised, sham-controlled, proof-of-concept trial. / Townsend, Raymond R; Mahfoud, Felix; Kandzari, David E; Kario, Kazuomi ; Pocock, Stuart J; Weber, Michael A.; Ewen, Sebastian; Tsioufis, Konstantinos ; Tousoulis, Dimitrios; Sharp, Andrew S.P.; Watkinson, Anthony F.; Schmieder, Roland Erich; Schmid, Axel; Choi, James W.; East, Cara; Walton, Anthony; Hopper, Ingrid; Cohen, Debbie L.; Wilensky, Robert; Lee, David P.; Ma, Adrian; Devireddy, Chandan M; Lea, Janice P; Lurz, Philipp C.; Fengler, Karl; Davies, Justin; Chapman, Neil; Cohen, Sidney A. ; DeBruin, Vanessa; Fahy, Martin P; Jones, Denise E.; Rothman, Martin T; Böhm, Michael.

In: The Lancet, Vol. 390, No. 10108, 11.11.2017, p. 2160-2170.

Research output: Contribution to journalArticleResearchpeer-review

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 J

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 Erich

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 P

AU - Jones, Denise E.

AU - Rothman, Martin T

AU - Böhm, Michael

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.

KW - renal denervation

KW - hypertension

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