The aim of this double-blind, randomized, sham-controlled study was to verify the blood pressure (BP)-lowering efficacy of externally delivered focused ultrasound for renal denervation (RDN).
Nonrandomized, first proof-of-concept study and experimental evidence suggested that noninvasive techniques of RDN emerged as an alternative approach of RDN to invasive technologies.
WAVE IV, an international, randomized (1 : 1) sham-controlled, double-blind prospective clinical study, was prematurely stopped. Patients were enrolled if office BP was at least 160 mmHg and 24-h ambulatory BP was at least 135 mmHg, while taking three or more antihypertensive medications. The treatment consisted of bilateral RDN using therapeutic levels of ultrasound energy and the sham consisted of bilateral application of diagnostic levels of ultrasound energy.
In the 81 treated patients neither changes in office BP at 12 and 24 weeks, nor changes in 24-h ambulatory BP at 24-week follow-up visit differed between the two groups significantly. Of note, no safety signal was observed. Adherence analysis disclosed full adherence in 77% at baseline and 82% at 6 months’ follow-up visit. Post hoc analysis revealed that stricter criteria for stabilization of BP at baseline were associated with a numerically greater change in 24-h ambulatory BP in the RDN group than in the sham group.
Our data did not prove that antihypertensive efficacy of the externally delivered focused ultrasound for RDN was greater than the sham effect. Stabilization of BP at baseline was identified as an important determinant of BP changes.
aDepartment of Nephrology and Hypertension, University Hospital of the Friedrich-Alexander University Erlangen-Nürnberg, Erlangen
bInstitute of Legal Medicine, Forensic Toxicology Department, Goethe University, Frankfurt/Main
cInstitute for Preventive Medicine, Mahlow, Germany
dKona Medical, Department of Surgery, Stanford School of Medicine, Stanford, California
eKona Medical, Bellevue, Washington, USA
fMedizinische Klinik I, Clemenshospital GmbH, Münster, Germany
gNIHR Barts Cardiovascular Biomedical Research Unit, William Harvey Research Institute
hSt Bartholomew's Hospital, London
iRenal Unit, Heart of England NHS Foundation Trust, Birmingham, UK
jKardiologie, Angiologie und Pneumologie, Universitätsklinikum Bonn, Bonn, Germany
kMercy Angiography, Auckland, New Zealand
lRoyal Exeter and Devon Hospital, Exeter, UK
mCardioVascular Center, Sankt Katharinen Hospital, Frankfurt, Germany
nCardiology Department, University Hospital Brno
oMedical Faculty, Masaryk University Brno
pI. International Clinical Research Center, St. Anne's University Hospital, 1st Department of Internal Medicine/Cardioangiology, Brno, Czech Republic
qMedizinische Klinik II, Kardiologie und Angiologie, Sana Kliniken Lübeck, Lübeck
rUniversitätsklinikum Hamburg-Eppendorf, III. Medizinische Klinik und Poliklinik Hamburg, Germany
sDepartment of Interventional Cardiology and Angiology, Institute of Cardiology, Warsaw, Poland
Correspondence to Roland E. Schmieder, University Hospital of the Friedrich-Alexander-University Erlangen-Nürnberg, Nephrology and Hypertension, Ulmenweg 18, Erlangen 91054, Germany. Tel: +9131 85 36245; fax: +9131 85 36215; e-mail: Roland.Schmieder@uk-erlangen.de, firstname.lastname@example.org
Abbreviations: ABPM, ambulatory BP monitoring; BP, blood pressure; eGFR, estimated glomerular filtration rate; ITT, intention to treat; MI, myocardial infarction; RDN, therapeutic renal denervation; SEM, standard error of the mean; SNS, sympathetic nervous system; TRH, treatment-resistant hypertension
Received 12 May, 2017
Revised 15 August, 2017
Accepted 4 September, 2017
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