Michael Böhm1, Kazuomi Kario2, David E Kandzari3, Felix Mahfoud4, Michael A Weber5, Roland E Schmieder6, Konstantinos Tsioufis7, Stuart Pocock8, Dimitris Konstantinidis7, James W Choi9, Cara East9, David P Lee10, Adrian Ma10, Sebastian Ewen11, Debbie L Cohen12, Robert Wilensky12, Chandan M Devireddy13, Janice Lea13, Axel Schmid6, Joachim Weil14, Tolga Agdirlioglu14, Denise Reedus3, Brian K Jefferson15, David Reyes15, Richard D'Souza16, Andrew S P Sharp17, Faisal Sharif18, Martin Fahy19, Vanessa DeBruin19, Sidney A Cohen20, Sandeep Brar19, Raymond R Townsend12. 1. Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg (Saar), Germany. Electronic address: michael.boehm@uks.eu. 2. Jichi Medical University School of Medicine, Tochigi, Japan. 3. Piedmont Heart Institute, Atlanta, GA, USA. 4. Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg (Saar), Germany; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA. 5. SUNY Downstate College of Medicine, Brooklyn, NY, USA. 6. Universitätsklinikum Erlangen, Erlangen, Germany. 7. National and Kapodistrian University of Athens, Hippocratio Hospital, Athens, Greece. 8. London School of Hygiene & Tropical Medicine, London, UK. 9. Baylor Scott and White Heart and Vascular Hospital, Dallas, TX, USA. 10. Stanford Hospital and Clinics, Stanford, CA, USA. 11. Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg (Saar), Germany. 12. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 13. Emory University School of Medicine, Atlanta, GA, USA. 14. Sana Cardiomed Heart Center, LÜbeck, Germany. 15. TriStar Centennial Medical Center, Nashville, TN, USA. 16. The Royal Devon and Exeter Hospital, Exeter, UK. 17. University Hospital of Wales, Cardiff, UK; University of Exeter, Exeter, UK. 18. Galway University Hospitals and National University of Ireland Galway, Galway, Ireland. 19. Medtronic, Santa Rosa, CA, USA. 20. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Medtronic, Santa Rosa, CA, USA.
Abstract
BACKGROUND: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. METHODS: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749. FINDINGS: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was -3·9 mm Hg (Bayesian 95% credible interval -6·2 to -1·6) and for office systolic blood pressure the difference was -6·5 mm Hg (-9·6 to -3·5). No major device-related or procedural-related safety events occurred up to 3 months. INTERPRETATION: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. FUNDING: Medtronic.
BACKGROUND: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. METHODS: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749. FINDINGS: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was -3·9 mm Hg (Bayesian 95% credible interval -6·2 to -1·6) and for office systolic blood pressure the difference was -6·5 mm Hg (-9·6 to -3·5). No major device-related or procedural-related safety events occurred up to 3 months. INTERPRETATION: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. FUNDING: Medtronic.