Raymond R Townsend1, Felix Mahfoud2, David E Kandzari3, Kazuomi Kario4, Stuart Pocock5, Michael A Weber6, Sebastian Ewen7, Konstantinos Tsioufis8, Dimitrios Tousoulis8, Andrew S P Sharp9, Anthony F Watkinson9, Roland E Schmieder10, Axel Schmid10, James W Choi11, Cara East11, Anthony Walton12, Ingrid Hopper13, Debbie L Cohen14, Robert Wilensky15, David P Lee16, Adrian Ma16, Chandan M Devireddy17, Janice P Lea17, Philipp C Lurz18, Karl Fengler18, Justin Davies19, Neil Chapman19, Sidney A Cohen14, Vanessa DeBruin20, Martin Fahy20, Denise E Jones20, Martin Rothman21, Michael Böhm7. 1. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: townsend@upenn.edu. 2. Department of Internal Medicine III, University Hospital of Saarland, Saarland University, Homburg/Saar, Germany; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA. 3. Piedmont Heart Institute, Atlanta, GA, USA. 4. Jichi Medical University School of Medicine, Tochigi, Japan. 5. London School of Hygiene & Tropical Medicine, London, UK. 6. SUNY Downstate College of Medicine, Brooklyn, NY, USA. 7. Department of Internal Medicine III, University Hospital of Saarland, Saarland University, Homburg/Saar, Germany. 8. University of Athens, Hippocration Hospital, Athens, Greece. 9. The Royal Devon and Exeter Hospital, Exeter, UK. 10. University Hospital Erlangen, Erlangen, Germany. 11. Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, TX, USA. 12. The Alfred Hospital and Monash University, Melbourne, VIC, Australia. 13. The Alfred Hospital, Melbourne, VIC, Australia. 14. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Medtronic PLC, Santa Rosa, CA, USA. 15. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 16. Stanford Hospital & Clinics, Stanford, CA, USA. 17. Emory University School of Medicine, Atlanta, GA, USA. 18. University of Leipzig-Heart Center, Leipzig, Germany. 19. Imperial College and Hammersmith Hospital, Imperial, London, UK. 20. Medtronic PLC, Santa Rosa, CA, USA. 21. Medtronic PLC, Santa Rosa, CA, USA; Barts Health Trust, London, UK.
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.
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.
Authors: Nandita Raikwar; Cameron Braverman; Peter M Snyder; Robert A Fenton; David K Meyerholz; Francois M Abboud; Sailesh C Harwani Journal: Am J Physiol Heart Circ Physiol Date: 2019-06-07 Impact factor: 4.733
Authors: Robert M Carey; David A Calhoun; George L Bakris; Robert D Brook; Stacie L Daugherty; Cheryl R Dennison-Himmelfarb; Brent M Egan; John M Flack; Samuel S Gidding; Eric Judd; Daniel T Lackland; Cheryl L Laffer; Christopher Newton-Cheh; Steven M Smith; Sandra J Taler; Stephen C Textor; Tanya N Turan; William B White Journal: Hypertension Date: 2018-11 Impact factor: 10.190