Hypertension urgencies in the SPYRAL HTN-OFF MED Pivotal trial

Abstract

The SPYRAL HTN-OFF MED Pivotal trial ( https://ichgcp.net/clinical-trials-registry/NCT02439749 ) demonstrated significant reductions in blood pressure (BP) after renal denervation (RDN) compared to sham control in the absence of anti-hypertensive medications. Prior to the 3-month primary endpoint, medications were immediately reinstated for patients who met escape criteria defined as office systolic BP (SBP) ≥ 180 mmHg or other safety concerns. Our objective was to compare the rate of hypertensive urgencies in RDN vs. sham control patients. Patients were enrolled with office SBP ≥ 150 and < 180 mmHg, office diastolic BP (DBP) ≥ 90 mmHg and mean 24 h SBP ≥ 140 and < 170 mmHg. Patients had been required to discontinue any anti-hypertensive medications and were randomized 1:1 to RDN or sham control. In this post-hoc analysis, cumulative incidence curves with Kaplan-Meier estimates of rate of patients meeting escape criteria were generated for RDN and sham control patients. There were 16 RDN (9.6%) and 28 sham control patients (17.0%) who met escape criteria between baseline and 3 months. There was a significantly higher rate of sham control patients meeting escape criteria compared to RDN for all escape patients (p = 0.032), as well as for patients with a hypertensive urgency with office SBP ≥ 180 mmHg (p = 0.046). Rate of escape was similar between RDN and sham control for patients without a measured BP exceeding 180 mmHg (p = 0.32). In the SPYRAL HTN-OFF MED Pivotal trial, RDN patients were less likely to experience hypertensive urgencies that required immediate use of anti-hypertensive medications compared to sham control.

Keywords: Blood pressure; Hypertension; Hypertensive urgency; Renal denervation.

Conflict of interest statement

Prof Weber is a consultant for Medtronic, ReCor, Ablative Solutions, Johnson & Johnson and Urovant. Prof Schmieder reports grants and personal fees from Medtronic, Recor, and Ablative Solutions. Dr. Kandzari reports institutional research/grant support from Biotronik, Boston Scientific, Cardiovascular Systems, Inc., Orbus Neich, Teleflex, Medtronic and Ablative Solutions; and personal consulting honoraria from Ablative Solutions, Cardiovascular Systems, Inc., Magenta Medical, Medtronic, and Terumo. Prof Townsend is a consultant for Medtronic, AXIO and Janssen, and receives royalties from UpToDate. Prof Mahfoud is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219), and Deutsche Herzstiftung and has received scientific support and speaker honoraria from Astra-Zeneca, Bayer, Boehringer Ingelheim, Medtronic and ReCor Medical. Prof Tsioufis receives payments from Medtronic for work as center PI. Prof Kario receives personal fees from Medtronic during the conduct of the study; grants from Teijin Pharma, Omron Helthcare, FUKUDA DENSHI, Bayer Yakuhin, A & D, Daiichi Sankyo, Mochida Pharmaceutical, EA pharma, Boehringer Ingelheim Japan, Tanabe Mitsubishi Pharma Corporation, Novartis Pharma K.K., Shionogi & Co., Terumo Corporation, MSD K.K., and Sanwa Kagaku Kenkyusho; personal fees from Bristol-Myers Squibb K.K., Takeda Pharmaceutical, Daiichi Sankyo, Omron Healthcare, Bayer Yakuhin, Mochida Pharmaceutical, and Sumitomo Dainippon Pharma outside the submitted work. Dr. Pocock reports personal fees from Medtronic outside the submitted work. Dr. Tatakis has nothing to disclose. Dr. Ewen received speaker's honorarium and/or travel support from Akcea Therapeutics, AstraZeneca, Bayer, Berlin Chemie, Bristol-Myers Squibb—Pfizer, Böhringer Ingelheim, Daiichi Sankyo, Kaneka Pharma, Medtronic, Novartis and Recor. Dr. Choi reports consulting fees from Medtronic outside the submitted work. Dr. East receives research support from Medtronic. Dr. Lee reports consulting fees and research grants from Medtronic and research grants from Ablative Solutions. Dr. Ma has nothing to disclose. Dr. Cohen receives consulting fees from Medtronic, Recor and Metavention. Dr. Wilensky has nothing to disclose. Dr. Devireddy reports personal consulting honoraria from Edwards Lifesciences, Medtronic, ReCor Medical, and Shockwave Medical. Dr. Lea has nothing to disclose. Dr. Schmid has nothing to report. Mr. Fahy is an employee of Medtronic. Prof Böhm is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project number 322900939) and reports personal fees from Abbott, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, ReCor Medical, Servier, and Vifor during the conduct of the study.

© 2022. The Author(s).

Figures

Fig. 1

Kaplan–Meier estimate of rate of patients meeting escape criteria for RDN and sham control groups for A all escape patients, B patients with sustained office systolic BP ≥ 180 mmHg between randomization and 3 months, and C escape patients due to other safety concerns