Belli, Anna-Maria

Coca, Antonio

Lee, Michael

Mancia, Giuseppe

Moss, Jonathan G.

Peregrin, Jan H.

Redon, Josep

Reekers, Jim A.

Schmieder, Roland E.

Tsioufis, Costas

Vorwerk, Dierk

English

PubMed

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Executive summary of the joint position paper on renal denervation of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) and the European Society of Hypertension (ESH)

Jonathan G. Moss

Anna-Maria Belli

Antonio Coca

Michael Lee

Giuseppe Mancia

Jan H. Peregrin

Josep Redon

Jim A. Reekers

Costas Tsioufis

Dierk Vorwerk

Roland E. Schmieder

Crossref

EXECUTIVE SUMMARYExecutive Summary of the Joint Position Paper on RenalDenervation of the Cardiovascular and InterventionalRadiological Society of Europe (CIRSE) and the European Societyof Hypertension (ESH)Jonathan G. Moss1 • Anna-Maria Belli2 • Antonio Coca3 • Michael Lee4 •Giuseppe Mancia5 • Jan H. Peregrin6 • Josep Redon7 • Jim A. Reekers8 •Costas Tsioufis9 • Dierk Vorwerk10 • Roland E. Schmieder11Received: 29 August 2016 / Accepted: 9 September 2016 / Published online: 22 September 2016 The Author(s) 2016. This article is published with open access at Springerlink.comIntroductionThis joint position paper, composed by an author group ofmembers of the Cardiovascular and Interventional Radio-logical Society of Europe (CIRSE) and the EuropeanSociety of Hypertension (ESH), is being published jointlyin the Cardiovascular and Interventional Radiology Journaland the Journal of Hypertension. The paper attempts toreview the evidence and provide some guidance and for-ward direction for this new and potentially still valuabletechnique. The article presented here is a brief executivesummary of the full paper which can be found on theCIRSE and ESH websites.MethodologyCIRSE and the ESH produced this joint position paperusing the following process. The formal decision of the twosocieties to draft a multidisciplinary joint position paperwas taken in November 2013, following the discussion onthe potential benefits of a joint statement on the occasion ofthe CIRSE annual meeting 2013 in Barcelona.Both societies identified and nominated recognisedexperts as members of the joint writing group for thedocument. In the case of CIRSE, the renal denervation taskforce, an already established group of senior interventionalradiologists and CIRSE members with significant experi-ence in performing renal artery denervation, representedthe society in the working group. In the case of ESH, the& Jonathan G. MossJonathan.Moss@glasgow.ac.uk1 Interventional Radiology Unit, North Glasgow UniversityHospitals, Gartnavel General Hospital, 1053 Great WesternRoad, Glasgow G12 0YN, UK2 Department of Radiology, St George’s Hospital,London SW17 0QT, UK3 Hypertension and Vascular Risk Unit, Department of InternalMedicine, Hospital Clı´nic (IDIBAPS), University ofBarcelona, Barcelona, Spain4 Department of Radiology, Beaumont Hospital, Dublin 9,Ireland5 University of Milano-Bicocca, Milan, Italy6 Department of Diagnostic and Interventional Radiology,Institute for Clinical and Experimental Medicine, Prague 4,Czech Republic7 Research Institute INCLIVA, University of Valencia andCIBERObn, ISCIII, Madrid, Spain8 University of Amsterdam, Department of Radiology,Academic Medical Centre, Amsterdam, The Netherlands9 Hippokration Hospital, National and Kapodistrian Universityof Athens, Athens, Greece10 Institute of Radiology, Klinikum Ingolstadt, Ingolstadt,Germany11 Nephrology and Hypertension, University Hospital Erlangen,Erlangen, Germany123Cardiovasc Intervent Radiol (2016) 39:1681–1683DOI 10.1007/s00270-016-1467-2eminent members of the joint writing group were selectedby the society’s council, based on their expertise.In early 2014, the first writing workshop was held and atimeline for the drafting process was agreed upon. In theperiod following the workshop, it was announced that theresults of the pivotal HTN-3 regulatory trial would soon bepublished. Therefore, a new timeline was devised to beable to take into account these important results.Once HTN-3 had been published, a critical review of thecurrently available position statements, peer-reviewedarticles and regulatory documents in the field of renaldenervation was performed with regard to methodology,results and conclusions. Several further drafting workshopsand teleconferences were held between the two groups todiscuss interpretations and plan the writing phase.The drafting process of this joint position paper allowedfor an extensive exchange among interventional radiolo-gists and hypertension specialists, and achieved a consen-sus document agreeable to all the contributors. However,the negative results of the first randomised controlled trialwith sham control of this therapy that were publishedduring the drafting process had a significant impact on theongoing assessment. The publication of this position paperintervenes at a point in time where renal artery denervationseems to have lost its momentum in Europe, but the jointwriting group deems it thus all the more important to give acomprehensive account of this therapy, including thepotential benefits and urgent need for more scientific dataof randomised trials.Review of ContentRenal denervation (RDN) was reported as an exciting newdevelopment for the treatment of resistant hypertension in2009 [1]. This minimally invasive technique gained rapidacceptance across the globe, although the majority ofprocedures were carried out in one country (Germany). TheSymplicity HTN-2 randomised trial [2] added furthersupportive evidence (both efficacy and safety) and by late2013 no fewer than 60 companies were investing in thetechnology. The global potential is obvious with 5–10 % ofhypertensive patients (a third of the world population)falling into the ‘‘resistant’’ category. They are a very high-risk group, and RDN has the potential to result in a markedreduction in cardiovascular morbidity and mortality.The Symplicity HTN-3 FDA regulatory randomisedtrial, which would prove pivotal in the assessment of thetherapy, included a sham arm and used ABPM in the lar-gest trial to date (n = 535). Therefore, it addressed manyof the shortcomings of the earlier trials. The results pub-lished in NEJM in March 2014 showed a failure to achievethe primary efficacy outcome in reducing office bloodpressure at 6 months compared to the sham procedure. Thesafety endpoint was met with a major adverse event rate of1.4 % [3].It is difficult to exaggerate the fallout from this trial andits effect across the globe was almost immediate and per-haps also exaggerated. There has been much criticism andpraise of HTN-3 and a wide range of opinions persist.Although RDN appears to be consistently safe across alltrials (albeit with limited short-term follow-up), the maincontroversy is with regard to efficacy and here the trialshave produced mixed and conflicting results. As a result ofHTN-3 in particular, there has been a dramatic reduction inthe use of RDN in all countries in the order of 80 %, andtwo major companies have withdrawn from the market.The trial was well designed but has been criticised inseveral respects. One hundred and eleven different inter-ventionists treated the 364 patients in the active arm (34 %of operators only carried out a single procedure). Themajority of patients (N = 253) did not have a successfulfour-quadrant ablation [4]. It must, however, be noted thatthe guidance technologies applicable to RDN (for exampleultrasound) continue to evolve and may offer a moreeffective denervation in the future.The interpretation of results also proved challenging.The anatomical studies of human renal nerve anatomy arelimited and inconsistent, and further research is needed toguide RDN devices for the future [5, 6]. RDN is currentlyseverely hampered by having no easy method to measurethe completeness of denervation, which largely remains a‘‘blind technique’’. Variations in the use of aldosteroneantagonists drug turbulence in HTN-3 may have introducedconfounders.There are lessons to be learned from previous RDN trialdesigns and this group remains interested in RDN, althoughhigh-quality research is needed before widespread adoptionof this expensive technology. This research should includesham arms, use of ABPM to select and monitor patients,objective assessment of drug adherence and long-termassessment of the renal artery and renal function. Thesetrials should be conducted in high-volume specialist cen-tres with the appropriate physician expertise in hyperten-sion management supported by well-trained and auditedinterventionists. Participation in clinical trials and reg-istries is strongly recommended.Compliance with Ethical StandardsConflict of Interest Anna-Maria Belli is a member of the BostonScientific Advisory Board. Giuseppe Mancia has received speaker’sor consultation fees from Actavis, Bayer, Bo¨hringer Ingelheim, Fer-rer, Lilly, Medtronic Vascular Inc, Menarini Int, Merck Serono, MSD,Novartis, Recordati, Sanofi, Servier and Takeda in the past24 months. Costas Tsioufis has received a Research Grant from StJude Medical and Travel Expenses and Honoraria from St. JudeMedical and Medtronic. Roland E. Schmieder has received Speaker1682 J. G. Moss et al.: CIRSE-ESH Position on renal denervation of the Cardiovascular and Interventional. . .123fees, Consultancy and Advisory Board fees, etc. from Kona Medical,Medtronic and Recor. All other authors declare that they have noconflicts of interest.Open Access This article is distributed under the terms of theCreative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricteduse, distribution, and reproduction in any medium, provided you giveappropriate credit to the original author(s) and the source, provide alink to the Creative Commons license, and indicate if changes weremade.References1. Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J,Bartus K, et al. Catheter-based renal sympathetic denervation forresistant hypertension: a multicentre safety and proof-of-principlecohort study. Lancet. 2009;373:1275–81.2. Symplicity HTN-2 Investigators, Esler MD, Krum H, Sobotka PA,Schlaich MP, Schmieder RE, Bo¨hm M. Renal sympatheticdenervation in patients with treatment-resistant hypertension(The Symplicity HTN-2 Trial): a randomised controlled trial.Lancet. 2010;376:1903–9.3. Bhatt DL, Kandzari DE, O’Neill WW, D’Agostino R, Flack JM,Katzen BT, et al. A controlled trial of renal denervation forresistant hypertension. N Engl J Med. 2014;370:1393–401.4. Kandzari DE, Bhatt DL, Brar S, Devireddy CM, Esler M, Fahy M,et al. Predictors of blood pressure response in the SYMPLICITYHTN-3 trial. Eur Heart J. 2015;36:219–27.5. Sakakura K, Ladich E, Cheng Q, Otsuka F, Yahagi K, Fowler DR,et al. Anatomic assessment of sympathetic peri-arterial renalnerves in man. J Am Coll Cardiol. 2014;64:635–43.6. Mahfoud F, Lu¨scher TF, Andersson B, Baumgartner I, Cifkova R,Dimario C, et al. Expert consensus document from the Europeansociety of cardiology on catheter-based renal denervation. EurHeart J. 2013;34:2149–57.J. G. Moss et al.: CIRSE-ESH Position on renal denervation of the Cardiovascular and Interventional. . . 1683123

CardioVascular and Interventional Radiology

Executive Summary of the Joint Position Paper on Renal Denervation of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) and the European Society of Hypertension (ESH)

Renal denervation (RDN) was reported as a novel exciting treatment for resistant hypertension in 2009. An initial randomized trial supported its efficacy and the technique gained rapid acceptance across the globe. However, a subsequent large blinded, sham arm randomized trial conducted in the USA (to gain Food and Drug Administration approval) failed to achieve its primary efficacy end point in reducing office blood pressure at 6 months. Published in 2014 this trial received both widespread praise and criticism. RDN has effectively stopped out with clinical trials pending further evidence. This joint consensus document representing the European Society of Hypertension and the Cardiovascular and Radiological Society of Europe attempts to distill the current evidence and provide future direction and guidanc

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Executive summary of the joint position paper on renal denervation of the Cardiovascular and Interventional Radiological Society of Europe and the European Society of Hypertension

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Executive summary of the joint position paper on renal denervation of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) and the European Society of Hypertension (ESH)

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