Endovascular Ultrasound Renal Denervation to Treat Hypertension
Authors: Azizi Michel , Saxena Manish , Wang Yale , Jenkins J. Stephen , Devireddy Chandan , Rader Florian , Fisher Naomi D. L. , Schmieder Roland E. , Mahfoud Felix , Lindsey Jason , Sanghvi Kintur , Todoran Thomas M. , Pacella John , Flack John , Daemen Joost , Sharp Andrew S. P. , Lurz Philipp , Bloch Michael J. , Weber Michael A. , Lobo Melvin D. , Basile Jan , Claude Lisa , Reeve-Stoffer Helen , McClure Candace K. , Kirtane Ajay J. ,   RADIANCE II Investigators and Collaborators, Mullin Christopher , McClure Candace K. , Thackeray Lisa , Wang Yongshi , Chertow Glenn , Chandra Venita , Dauerman Harold , Kahan Thomas , Ullery Steven , Beohar Nirat , Dogan Ozgen , Mokrzycki Michelle , Mullaney Scott , Redfors Bjorn , Vefali Huseng , Loening Andreas , Zagoria Ron , Skeik Nedaa , Bae Richard , McMeans Amy , Goldman JoAnne , Peterson Rose , Tutor Isabelle , Harrison Michael , Penning Angel , Lea Janice , Fiebach Amanda , Merlin Claudia , Dohad Suhail , Tran Anne , Bhatia Kirin , Sobieszczyk Piotr , Halliday Ian , Munson Tay , Laster Steven , Bunte Mathew , Hart Anthony , King Dana , Hall Jamie , Krathen Courtney , Lewis Luot , Willitts Ashley , Awkar Anthony , Palmer Casey , Tecklenburg Anna , Schindler John , Muldoon Matthew , Albright MaryJo , Nicholson Tracy , Chami Youseff , Hafiz Abdul Moiz , Starkey Emily , Adams Kristal , Bernardo Nelson , Veis Judith , Hashim Hayder , Singh Suman , Whitman Donna , Stouffer Rick , Hinderliter Alan , Allen Meghan , Scholl Tatum , Fong Pete , Gainer James , Crook Sherron , Hatchcock Ellen , Cohen Debbie , Giri Jay , Kobayashi Taisei , Neubauer Robin , Naidu Suveeksha , Radhakrishnan Jai , Batres Candido , Edwards Suzanne , Khuddus Matheen , Zentko Suzanne , Touchton Abby , Roberson Marti , Akinapelli Abhilash , English Lisa , Neumann Bridget , Mendelsohn Farrel , Brantley Hutton , Cawthon Thomas , DeRamus Susan , Wade Wesley , Fishman Robert , Tuohy Edward , LeBlanc Jessica , McCurry Tina , Krishnaswamy Amar , Laffin Luke , Bajzer Christopher , Boros Marilyn , Branche Monica , Abraham Josephine , Abraham Anu , Stijleman  Inge , Hsi David , Martin Scott , Portnay Edward , Fiebach Maryann , Garavito Carolina , Adams Todd , Teklinski Andrew , Leech Adam , Drilling Patrick , Tulik Lynda , Benzuly Keith , Paparello James , Fintel Dan , Ramirez Haydee , Kats Lauren , Huang Paul , Biswas Santanu , Risher Serena , Pratt Kristina , Ibebuogu Uzoma , Johnson Karen , Cushman William , Jones Lisa , Jackson Leigh , Landers David , Pasala Tilak , Salazer Thomas , Canino Peter , Arakelian Patricia , Yang Yi-Ming , Khaliq Asma , Weinberg Mitchell , Abetu Yihenew , Gulliver Alana , Reilly JP , Garasic Joseph , Chugh Atul , Bertolet Barry , Go Brian , Gollapudi Raghava , Cohn Joel , Rogers Kevin , Mathur Anthony , Jain Ajay , Balawon Armida , Zongo Oliver , Topham Christine , Anderson Richard , Thompson Elizabeth , Spiro Nikki , Hodges Elizabeth , Ellam Timothy , Bagnall Alan , Jackson Ralph , Bridgett Victoria , Wilson Peter , Das Neelanjan , Doulton Timothy , Loader David , Hector Gemma , Levy Terry , Bent Clare , Kodoth Vivek , Horler Stephanie , Nix Sara , Robinson Nicholas , Al-Janabi Firas , Sayer Jeremy , Iyer Sudha Ganesh , Redman Emily , Ramirez Jonaifah , Padmanabhan Sandosh , Sharif Faisal , Alhmoudi Aishah , Lunardi Mattia , Coen Eileen , Glynn Nicola , Lauder Lucas , Kulenthiran Saarraaken , Koch Christina , Wachter Angelika , Schmid Axel , Kannenkeril Dennis , Heinritz Ulrike , Endres-Frohlich Kerstin , Rommel Karl Philipp , Fengler Karl  , Petzold Martin , Büttner Margit , Weil Joachim , Agdirlioglu Tolga , Köllner Tanja , Stephan Jeannine , Dagkonakis Nikolaos , Hamann Frank , Ettl Ute , Petzsche Ulrike , Reimer Peter , Hausberg Martin , Hinrichs Ralf , Di Ponio-Voit Isabella , Lutz Matthias , Gosse Philippe , Cremer Antoine , Papadopoulos Panteleimon , Gaudissard Julie , Maire Florent , Sapoval Marc , Livrozet Marine , Regrag Asma , Paquet Valerie , Delsart Pascal , Hennicaux Justin , Sommeville Coralie , Bertrand Fabien , Lafeber Melvin , Zeijen Victor , Ruiter Amo , van Ramshorst Jan , Xaplanteris Panagiotis , Briki Rachid , de Hemptinne Quentin , Pascal Severine , Renard Katty , Lefebvre Pascal , Ferdinande Bert , Iglesias Juan F. , Ehret Georg , Gallego Laetitia , Dobretz Kevin 
Published: February 2023

Importance

Two initial sham-controlled trials demonstrated that ultrasound renal denervation decreases blood pressure (BP) in patients with mild to moderate hypertension and hypertension that is resistant to treatment.

Objective

To study the efficacy and safety of ultrasound renal denervation without the confounding influence of antihypertensive medications in patients with hypertension.

Design, Setting, and Participants

Sham-controlled, randomized clinical trial with patients and outcome assessors blinded to treatment assignment that was conducted between January 14, 2019, and March 25, 2022, at 37 centers in the US and 24 centers in Europe, with randomization stratified by center. Patients aged 18 years to 75 years with hypertension (seated office systolic BP [SBP] ≥140 mm Hg and diastolic BP [DBP] ≥90 mm Hg despite taking up to 2 antihypertensive medications) were eligible if they had an ambulatory SBP/DBP of 135/85 mm Hg or greater and an SBP/DBP less than 170/105 mm Hg after a 4-week washout of their medications. Patients with an estimated glomerular filtration rate of 40 mL/min/1.73 m2 or greater and with suitable renal artery anatomy were randomized 2:1 to undergo ultrasound renal denervation or a sham procedure. Patients were to abstain from antihypertensive medications until the 2-month follow-up unless prespecified BP criteria were exceeded and were associated with clinical symptoms.

Interventions

Ultrasound renal denervation vs a sham procedure.

Main Outcomes and Measures

The primary efficacy outcome was the mean change in daytime ambulatory SBP at 2 months. The primary safety composite outcome of major adverse events included death, kidney failure, and major embolic, vascular, cardiovascular, cerebrovascular, and hypertensive events at 30 days and renal artery stenosis greater than 70% detected at 6 months. The secondary outcomes included mean change in 24-hour ambulatory SBP, home SBP, office SBP, and all DBP parameters at 2 months.

Results

Among 1038 eligible patients, 150 were randomized to ultrasound renal denervation and 74 to a sham procedure (mean age, 55 years [SD, 9.3 years]; 28.6% female; and 16.1% self-identified as Black or African American). The reduction in daytime ambulatory SBP was greater with ultrasound renal denervation (mean, −7.9 mm Hg [SD, 11.6 mm Hg]) vs the sham procedure (mean, −1.8 mm Hg [SD, 9.5 mm Hg]) (baseline-adjusted between-group difference, −6.3 mm Hg [95% CI, −9.3 to −3.2 mm Hg], P &amp;lt; .001), with a consistent effect of ultrasound renal denervation throughout the 24-hour circadian cycle. Among 7 secondary BP outcomes, 6 were significantly improved with ultrasound renal denervation vs the sham procedure. No major adverse events were reported in either group.

Conclusions and Relevance

In patients with hypertension, ultrasound renal denervation reduced daytime ambulatory SBP at 2 months in the absence of antihypertensive medications vs a sham procedure without postprocedural major adverse events.

Trial Registration

ClinicalTrials.gov Identifier: NCT03614260