David E Kandzari1, Deepak L Bhatt2, Sandeep Brar3, Chandan M Devireddy4, Murray Esler5, Martin Fahy3, John M Flack6, Barry T Katzen7, Janice Lea4, David P Lee8, Martin B Leon9, Adrian Ma8, Joseph Massaro10, Laura Mauri11, Suzanne Oparil12, William W O'Neill13, Manesh R Patel14, Krishna Rocha-Singh15, Paul A Sobotka16, Laura Svetkey14, Raymond R Townsend17, George L Bakris18. 1. Piedmont Heart Institute, Atlanta, GA, USA david.kandzari@piedmont.org. 2. Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA, USA. 3. Medtronic, Inc., Santa Rosa, CA, USA. 4. Emory University School of Medicine, Atlanta, GA, USA. 5. Baker IDI Heart and Diabetes Institute, Monash University, Melbourne, Australia. 6. Wayne State University and the Detroit Medical Center, Detroit, MI, USA. 7. Baptist Cardiac and Vascular Institute, Miami, FL, USA. 8. Stanford Hospital and Clinics, Palo Alto, CA, USA. 9. New York Presbyterian Hospital, Columbia University Medical Center and Cardiovascular Research Foundation, New York, NY, USA. 10. Harvard Clinical Research Institute, Boston, MA, USA. 11. Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA, USA Harvard Clinical Research Institute, Boston, MA, USA. 12. University of Alabama at Birmingham, Birmingham, AL, USA. 13. Division of Cardiology, Henry Ford Hospital, Detroit, MI, USA. 14. Duke University Medical Center, Durham, NC, USA. 15. Prairie Heart Institute, Springfield, IL, USA. 16. The Ohio State University, Columbus, OH, USA. 17. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 18. The University of Chicago Medicine, Chicago, IL, USA.
Abstract
AIMS: The SYMPLICITY HTN-3 randomized, blinded, sham-controlled trial confirmed the safety of renal denervation (RDN), but did not meet its primary efficacy endpoint. Prior RDN studies have demonstrated significant and durable reductions in blood pressure. This analysis investigated factors that may help explain these disparate results. METHODS AND RESULTS:Patients with resistant hypertension were randomized 2 : 1 to RDN (n = 364) or sham (n = 171). The primary endpoint was the difference in office systolic blood pressure (SBP) change at 6 months. A multivariable analysis identified predictors of SBP change. Additional analyses examined the influence of medication changes, results in selected subgroups and procedural factors. Between randomization and the 6-month endpoint, 39% of patients underwent medication changes. Predictors of office SBP reduction at 6 months were baseline office SBP ≥ 180 mmHg, aldosterone antagonist use, and non-use of vasodilators; number of ablations was a predictor in the RDN group. Non-African-American patients receiving RDN had a significantly greater change in office SBP than those receiving sham; -15.2 ± 23.5 vs. -8.6 ± 24.8 mmHg, respectively (P = 0.012). Greater reductions in office and ambulatory SBP, and heart rate were observed with a higher number of ablations and energy delivery in a four-quadrant pattern. CONCLUSIONS: Post hoc analyses, although derived from limited patient cohorts, reveal several potential confounding factors that may partially explain the unexpected blood pressure responses in both the sham control and RDN groups. These hypothesis-generating data further inform the design of subsequent research to evaluate the potential role of RDN in the treatment of resistant hypertension. CLINICALTRIALS.GOV IDENTIFIER: NCT01418261. Published on behalf of the European Society of Cardiology. All rights reserved.
RCT Entities:
AIMS: The SYMPLICITY HTN-3 randomized, blinded, sham-controlled trial confirmed the safety of renal denervation (RDN), but did not meet its primary efficacy endpoint. Prior RDN studies have demonstrated significant and durable reductions in blood pressure. This analysis investigated factors that may help explain these disparate results. METHODS AND RESULTS:Patients with resistant hypertension were randomized 2 : 1 to RDN (n = 364) or sham (n = 171). The primary endpoint was the difference in office systolic blood pressure (SBP) change at 6 months. A multivariable analysis identified predictors of SBP change. Additional analyses examined the influence of medication changes, results in selected subgroups and procedural factors. Between randomization and the 6-month endpoint, 39% of patients underwent medication changes. Predictors of office SBP reduction at 6 months were baseline office SBP ≥ 180 mmHg, aldosterone antagonist use, and non-use of vasodilators; number of ablations was a predictor in the RDN group. Non-African-American patients receiving RDN had a significantly greater change in office SBP than those receiving sham; -15.2 ± 23.5 vs. -8.6 ± 24.8 mmHg, respectively (P = 0.012). Greater reductions in office and ambulatory SBP, and heart rate were observed with a higher number of ablations and energy delivery in a four-quadrant pattern. CONCLUSIONS: Post hoc analyses, although derived from limited patient cohorts, reveal several potential confounding factors that may partially explain the unexpected blood pressure responses in both the sham control and RDN groups. These hypothesis-generating data further inform the design of subsequent research to evaluate the potential role of RDN in the treatment of resistant hypertension. CLINICALTRIALS.GOV IDENTIFIER: NCT01418261. Published on behalf of the European Society of Cardiology. All rights reserved.
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