{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T23:40:58Z","timestamp":1789342858499,"version":"build-2803163510"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004374","name":"Medtronic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004374","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Res Cardiol"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The SPYRAL HTN-OFF MED Pivotal trial (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02439749\">https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02439749<\/jats:ext-link>) 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)\u2009\u2265\u2009180\u00a0mmHg 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\u2009\u2265\u2009150 and\u2009&lt;\u2009180\u00a0mmHg, office diastolic BP (DBP)\u2009\u2265\u200990\u00a0mmHg and mean 24\u00a0h SBP\u2009\u2265\u2009140 and\u2009&lt;\u2009170\u00a0mmHg. 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\u2013Meier 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\u00a0months. There was a significantly higher rate of sham control patients meeting escape criteria compared to RDN for all escape patients (<jats:italic>p<\/jats:italic>\u2009=\u20090.032), as well as for patients with a hypertensive urgency with office SBP\u2009\u2265\u2009180\u00a0mmHg (<jats:italic>p<\/jats:italic>\u2009=\u20090.046). Rate of escape was similar between RDN and sham control for patients without a measured BP exceeding 180\u00a0mmHg (<jats:italic>p<\/jats:italic>\u2009=\u20090.32). 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.<\/jats:p>\n                <jats:p><jats:bold>Graphical abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s00392-022-02064-5","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T10:03:07Z","timestamp":1658224987000},"page":"1269-1275","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Hypertension urgencies in the SPYRAL HTN-OFF MED Pivotal trial"],"prefix":"10.1007","volume":"111","author":[{"given":"Michael A.","family":"Weber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland E.","family":"Schmieder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Kandzari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond R.","family":"Townsend","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Mahfoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Tsioufis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuomi","family":"Kario","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Pocock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fotis","family":"Tatakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Ewen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara","family":"East","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie L.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Wilensky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandan M.","family":"Devireddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice P.","family":"Lea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Schmid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Fahy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"B\u00f6hm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"2064_CR1","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/S0140-6736(05)17741-1","volume":"365","author":"PM Kearney","year":"2005","unstructured":"Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J (2005) Global burden of hypertension: analysis of worldwide data. Lancet 365:217\u2013223","journal-title":"Lancet"},{"key":"2064_CR2","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.1016\/j.jacc.2017.11.005","volume":"71","author":"PK Whelton","year":"2018","unstructured":"Whelton PK, Carey RM, Aronow WS et al (2018) 2017 ACC\/AHA\/AAPA\/ABC\/ACPM\/AGS\/APhA\/ASH\/ASPC\/NMA\/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of The American College Of Cardiology\/American Heart Association Task Force On Clinical Practice Guidelines. J Am Coll Cardiol 71:2199\u20132269","journal-title":"J Am Coll Cardiol"},{"key":"2064_CR3","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1161\/CIRCRESAHA.118.313220","volume":"124","author":"M Burnier","year":"2019","unstructured":"Burnier M, Egan BM (2019) Adherence in hypertension. Circ Res 124:1124\u20131140","journal-title":"Circ Res"},{"key":"2064_CR4","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1097\/HJH.0000000000002842","volume":"39","author":"L Lauder","year":"2021","unstructured":"Lauder L, Ewen S, Glasmacher J et al (2021) Drug adherence and psychosocial characteristics of patients presenting with hypertensive urgency at the emergency department. J Hypertens 39:1697\u20131704","journal-title":"J Hypertens"},{"key":"2064_CR5","doi-asserted-by":"publisher","first-page":"2335","DOI":"10.1016\/S0140-6736(18)31082-1","volume":"391","author":"M Azizi","year":"2018","unstructured":"Azizi M, Schmieder RE, Mahfoud F et al (2018) Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial. Lancet 391:2335\u20132345","journal-title":"Lancet"},{"key":"2064_CR6","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1016\/S0140-6736(20)30554-7","volume":"395","author":"M Bohm","year":"2020","unstructured":"Bohm M, Kario K, Kandzari DE et al (2020) Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet 395:1444\u20131451","journal-title":"Lancet"},{"key":"2064_CR7","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s00392-020-01595-z","volume":"109","author":"M Bohm","year":"2020","unstructured":"Bohm M, Townsend RR, Kario K et al (2020) Rationale and design of two randomized sham-controlled trials of catheter-based renal denervation in subjects with uncontrolled hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) and presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications: a novel approach using Bayesian design. Clin Res Cardiol 109:289\u2013302","journal-title":"Clin Res Cardiol"},{"key":"2064_CR8","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1111\/jch.13083","volume":"19","author":"H Guiga","year":"2017","unstructured":"Guiga H, Decroux C, Michelet P et al (2017) Hospital and out-of-hospital mortality in 670 hypertensive emergencies and urgencies. J Clin Hypertens (Greenwich) 19:1137\u20131142","journal-title":"J Clin Hypertens (Greenwich)"},{"key":"2064_CR9","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1097\/HJH.0000000000001582","volume":"36","author":"A Persu","year":"2018","unstructured":"Persu A, Gordin D, Jacobs L et al (2018) Blood pressure response to renal denervation is correlated with baseline blood pressure variability: a patient-level meta-analysis. J Hypertens 36:221\u2013229","journal-title":"J Hypertens"},{"key":"2064_CR10","doi-asserted-by":"publisher","first-page":"i4098","DOI":"10.1136\/bmj.i4098","volume":"354","author":"SL Stevens","year":"2016","unstructured":"Stevens SL, Wood S, Koshiaris C et al (2016) Blood pressure variability and cardiovascular disease: systematic review and meta-analysis. BMJ 354:i4098","journal-title":"BMJ"},{"key":"2064_CR11","doi-asserted-by":"publisher","first-page":"2346","DOI":"10.1016\/S0140-6736(18)30951-6","volume":"391","author":"DE Kandzari","year":"2018","unstructured":"Kandzari DE, Bohm M, Mahfoud F et al (2018) Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet 391:2346\u20132355","journal-title":"Lancet"},{"key":"2064_CR12","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s11906-006-0051-6","volume":"8","author":"G Parati","year":"2006","unstructured":"Parati G, Faini A, Valentini M (2006) Blood pressure variability: its measurement and significance in hypertension. Curr Hypertens Rep 8:199\u2013204","journal-title":"Curr Hypertens Rep"},{"key":"2064_CR13","doi-asserted-by":"publisher","first-page":"3845690","DOI":"10.1155\/2019\/3845690","volume":"2019","author":"A Berukstis","year":"2019","unstructured":"Berukstis A, Navickas R, Neverauskaite-Piliponiene G et al (2019) Arterial destiffening starts early after renal artery denervation. Int J Hypertens 2019:3845690","journal-title":"Int J Hypertens"}],"container-title":["Clinical Research in Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00392-022-02064-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00392-022-02064-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00392-022-02064-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T22:03:46Z","timestamp":1667253826000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00392-022-02064-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,19]]},"references-count":13,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["2064"],"URL":"https:\/\/doi.org\/10.1007\/s00392-022-02064-5","relation":{},"ISSN":["1861-0684","1861-0692"],"issn-type":[{"value":"1861-0684","type":"print"},{"value":"1861-0692","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,19]]},"assertion":[{"value":"12 May 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 July 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"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\u00a0institutional 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 f\u00fcr 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\u2014Pfizer, B\u00f6hringer 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 B\u00f6hm 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.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}