Skip to main content
SpringerLink
Log in

Appraisal of the Clinical Trial Data on Renal Denervation for the Management of Resistant Hypertension

  • Chapter
  • First Online:
Renal Denervation

  • 885 Accesses

Abstract

Over the past decade several national and international societies/regulatory bodies have proposed definitions of resistant hypertension (RHTN) (Table 5.1). There are subtle differences between these definitions, but treatment-resistant systemic HTN can be described as a blood pressure (BP) that remains uncontrolled (i.e., seated office BP >140/90 mmHg) despite adherence to treatment with at least three complementary antihypertensive agents (one of which is a diuretic) already taken at optimal or best-tolerated doses [1, 3, 11, 12]. In the UK, the National Institute for Health and Care Excellence (NICE) Clinical Guideline 127 [13] (Table 5.1) has been more proscriptive with their definition by suggesting that the three antihypertensives would usually be a regimen of an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) plus a calcium channel blocker plus a thiazide-type diuretic (i.e., A+C+D regimen), in accordance with the NICE treatment algorithm (http://guidance.nice.org.uk/CG127). The NICE guidance has also suggested that RHTN should only be diagnosed after confirming inadequate BP control by use of ambulatory blood pressure monitoring (ABPM – i.e., mean daytime BP >135/85), thereby excluding so-called “white coat” hypertension. The optimal target BP in patients treated for RHTN is widely accepted to be <140/90 mmHg, although lower targets might be appropriate in those with diabetes and/or chronic kidney disease (CKD) (Table 5.1) [11]. Furthermore, it should be remembered that an individual whose BP is controlled by the incorporation of a 4th line agent continues to be labelled as having RHTN. Likewise, RHTN should not be confused with uncontrolled HTN, the latter being an umbrella term to include all those individuals unable to achieve adequate BP targets, including that due to non-adherence, despite therapeutic intervention.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 59.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 79.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Chobanian A, Bakris G, Black H, Cushman WC, Green LA, Izzo Jr JL, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The JNC 7 report. JAMA. 2003;289:2560–72.

    Article  CAS  PubMed  Google Scholar 

  2. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2007;28:1462–536.

    PubMed  Google Scholar 

  3. Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, et al. Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension. 2008;51:1403–19.

    Article  CAS  PubMed  Google Scholar 

  4. National Clinical Guideline Centre. CG127 Hypertension: the clinical management of primary hypertension in adults. 2011. p. 1–328.

    Google Scholar 

  5. Caulfield M, Belder M De, Cleveland T, Collier D, Gray H, Knight C, et al. Joint UK Societies’ consensus summary statement on renal denervation for resistant hypertension. 2011. p. 1–2.

    Google Scholar 

  6. Schmieder RE, Redon J, Grassi G, Kjeldsen SE, Mancia G, Narkiewicz K, et al. ESH position paper: renal denervation – an interventional therapy of resistant hypertension. J Hypertens. 2012;30:837–41.

    Article  CAS  PubMed  Google Scholar 

  7. Weber MA, Schiffrin EL, White WB, Mann S, Lindholm LH, Kenerson JG, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens. 2014;16:14–26.

    Article  Google Scholar 

  8. Mahfoud F, Lüscher TF, Andersson B, Baumgartner I, Cifkova R, Dimario C, et al. Expert consensus document from the European Society of Cardiology on catheter-based renal denervation. Eur Heart J. 2013;34:2149–57.

    Article  PubMed  Google Scholar 

  9. Schlaich MP, Schmieder RE, Bakris G, Blankestijn PJ, Böhm M, Campese VM, et al. International expert consensus statement: percutaneous transluminal renal denervation for the treatment of resistant hypertension. J Am Coll Cardiol. 2013;62:2031–45.

    Article  PubMed  Google Scholar 

  10. Tsioufis C, Mahfoud F, Mancia G, Redon J, Damascelli B, Zeller T, et al. What the interventionalist should know about renal denervation in hypertensive patients: a position paper by the ESH WG on the interventional treatment of hypertension. EuroIntervention. 2014;9:1027–35.

    PubMed  Google Scholar 

  11. Myat A, Redwood SR, Qureshi AC, Spertus JA, Williams B. Resistant hypertension. BMJ. 2012;345:e7473.

    Article  PubMed  Google Scholar 

  12. Myat A, Redwood SR, Qureshi AC, Thackray S, Cleland JGF, Bhatt DL, et al. Renal sympathetic denervation therapy for resistant hypertension: a contemporary synopsis and future implications. Circ Cardiovasc Interv. 2013;6:184–97.

    Article  PubMed  Google Scholar 

  13. Kumbhani DJ, Steg PG, Cannon CP, Eagle KA, Smith SC, Crowley K, et al. Resistant hypertension: a frequent and ominous finding among hypertensive patients with atherothrombosis. Eur Heart J. 2013;34:1204–14.

    Article  CAS  PubMed  Google Scholar 

  14. Daugherty SL, Powers JD, Magid DJ, Tavel HM, Masoudi FA, Margolis KL, et al. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation. 2012;125:1635–42.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Egan BM, Zhao Y, Axon RN, Brzezinski W, Ferdinand KC. Uncontrolled and apparent treatment resistant hypertension in the United States, 1988 to 2008. Circulation. 2011;124:1046–58.

    Article  PubMed Central  PubMed  Google Scholar 

  16. De la Sierra A, Segura J, Banegas JR, Gorostidi M, de la Cruz JJ, Armario P, et al. Clinical features of 8295 patients with resistant hypertension classified on the basis of ambulatory blood pressure monitoring. Hypertension. 2011;57:898–902.

    Article  PubMed  Google Scholar 

  17. Pimenta E, Calhoun DA. Resistant hypertension: incidence, prevalence, and prognosis. Circulation. 2012;125:1594–6.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Esler M. The sympathetic nervous system through the ages: from Thomas Willis to resistant hypertension. Exp Physiol. 2011;96:611–22.

    PubMed  Google Scholar 

  19. DiBona GF, Esler M. Translational medicine: the antihypertensive effect of renal denervation. Am J Physiol Regul Integr Comp Physiol. 2010;298:R245–53.

    Article  CAS  PubMed  Google Scholar 

  20. Oliveria SA, Lapuerta P, McCarthy BD, L’Italien GJ, Berlowitz DR, Asch SM. Physician-related barriers to the effective management of uncontrolled hypertension. Arch Intern Med. 2002;162:413–20.

    Article  PubMed  Google Scholar 

  21. Banegas JR, Messerli FH, Waeber B, Rodríguez-Artalejo F, de la Sierra A, Segura J, et al. Discrepancies between office and ambulatory blood pressure: clinical implications. Am J Med. 2009;122:1136–41. Elsevier Inc.

    Article  PubMed  Google Scholar 

  22. National Institute for Health and Clinical Excellence. Percutaneous transluminal radiofrequency sympathetic denervation of the renal artery for resistant hypertension. NICE Interventional Procedure Guidance 418. 2012. p. 1–10.

    Google Scholar 

  23. Mancia G, Bombelli M, Facchetti R, Madotto F, Quarti-Trevano F, Polo Friz H, et al. Long-term risk of sustained hypertension in white-coat or masked hypertension. Hypertension. 2009;54:226–32.

    Article  CAS  PubMed  Google Scholar 

  24. Fagard RH. Resistant hypertension. Heart. 2012;98:254–61.

    Article  CAS  PubMed  Google Scholar 

  25. Sarafidis PA, Bakris GL. Resistant hypertension: an overview of evaluation and treatment. J Am Coll Cardiol. 2008;52:1749–57. American College of Cardiology Foundation.

    Article  PubMed  Google Scholar 

  26. Acelajado MC, Calhoun D, Oparil S. Reduction of blood pressure in patients with treatment-resistant hypertension. Expert Opin Pharmacother. 2009;10:2959–71.

    Article  CAS  PubMed  Google Scholar 

  27. Ishikawa J, Carroll DJ, Kuruvilla S, Schwartz JE, Pickering TG. Changes in home versus clinic blood pressure with antihypertensive treatments: a meta-analysis. Hypertension. 2008;52:856–64.

    Article  CAS  PubMed  Google Scholar 

  28. Mancia G, Parati G. Office compared with ambulatory blood pressure in assessing response to antihypertensive treatment: a meta-analysis. J Hypertens. 2004;22:435–45.

    Article  CAS  PubMed  Google Scholar 

  29. Mancia G, Sega R, Bravi C, De Vito G, Valagussa F, Cesana G, et al. Ambulatory blood pressure normality: results from the PAMELA study. J Hypertens. 1995;13:1377–90.

    Article  CAS  PubMed  Google Scholar 

  30. Dolan E, Stanton A, Thijs L, Hinedi K, Atkins N, McClory S, et al. Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study. Hypertension. 2005;46:156–61.

    Article  CAS  PubMed  Google Scholar 

  31. Pickering TG, White WB. When and how to use self (home) and ambulatory blood pressure monitoring. J Am Soc Hypertens. 2008;2:119–24.

    Article  PubMed  Google Scholar 

  32. Salles GF, Cardoso CRL, Muxfeldt ES. Prognostic influence of office and ambulatory blood pressures in resistant hypertension. Arch Intern Med. 2008;168:2340–6.

    Article  PubMed  Google Scholar 

  33. Yakovlevitch M, Black HR. Resistant hypertension in a tertiary care clinic. Arch Intern Med. 1991;151:1786–92.

    Article  CAS  PubMed  Google Scholar 

  34. Garg JP, Elliott WJ, Folker A, Izhar M, Black HR. Resistant hypertension revisited: a comparison of two university-based cohorts. Am J Hypertens. 2005;18:619–26.

    Article  PubMed  Google Scholar 

  35. Pimenta E, Gaddam K, Oparil S. Mechanisms and treatment of resistant hypertension. J Clin Hypertens. 2008;10:239–44.

    Article  CAS  Google Scholar 

  36. Verloop WL, Vink EE, Voskuil M, Vonken E-J, Rookmaaker MB, Bots ML, et al. Eligibility for percutaneous renal denervation: the importance of a systematic screening. J Hypertens. 2013;31:1662–8.

    Article  CAS  PubMed  Google Scholar 

  37. Schlaich MP, Sobotka P, Krum H, Lambert E, Esler MD. Renal sympathetic-nerve ablation for uncontrolled hypertension. N Engl J Med. 2009;361:932–4.

    Article  CAS  PubMed  Google Scholar 

  38. Krum H, Schlaich M, Whitbourn R, Sobotka P, Sadowski J, Bartus K, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;373:1275–81.

    Article  PubMed  Google Scholar 

  39. Krum H, Schlaich MP, Böhm M, Mahfoud F, Rocha-Singh K, Katholi R, et al. Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the Symplicity HTN-1 study. Lancet. 2013;383:622–9.

    Article  PubMed  Google Scholar 

  40. Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Böhm M. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010;376:1903–9.

    Article  PubMed  Google Scholar 

  41. Symplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension. 2011;57:911–7.

    Article  Google Scholar 

  42. Esler MD, Krum H, Schlaich M, Schmieder RE, Böhm M, Sobotka PA. Renal sympathetic denervation for treatment of drug-resistant hypertension: one-year results from the symplicity HTN-2 randomized, controlled trial. Circulation. 2012;126:2976–82.

    Article  CAS  PubMed  Google Scholar 

  43. Medtronic. SymplicityTM RDN System Clinical Trial Data [Internet]. 2014. Available from: http://www.medtronicrdn.com/intl/healthcare-professionals/symplicity-rdn-system/symplicity-clinical-trial-data/index.htm.

  44. Virmani R. Perirenal nerve distribution, density and quantification: implications for the evaluation of device safety and efficacy disclosure statement of financial interest. Transcatheter Cardiovascular Therapeutics, Miami; 2012.

    Google Scholar 

  45. Johns EJ. Resistant hypertension and renal denervation: 3 years on. Lancet. 2014;383:583–4.

    Article  PubMed  Google Scholar 

  46. Doumas M, Douma S. Interventional management of resistant hypertension. Lancet. 2009;373:1228–30.

    Article  PubMed  Google Scholar 

  47. Doumas M, Anyfanti P, Bakris G. Should ambulatory blood pressure monitoring be mandatory for future studies in resistant hypertension: a perspective. J Hypertens. 2012;30:874–6.

    Article  CAS  PubMed  Google Scholar 

  48. Vonend O, Antoch G, Rump LC, Blondin D. Secondary rise in blood pressure after renal denervation. Lancet. 2012;380:778.

    Article  PubMed  Google Scholar 

  49. Kaltenbach B, Id D, Franke JC, Sievert H, Hennersdorf M, Maier J, et al. Renal artery stenosis after renal sympathetic denervation. J Am Coll Cardiol. 2012;60:2694–5.

    Article  PubMed  Google Scholar 

  50. Mahfoud F, Cremers B, Janker J, Link B, Vonend O, Ukena C, et al. Renal hemodynamics and renal function after catheter-based renal sympathetic denervation in patients with resistant hypertension. Hypertension. 2012;60:419–24.

    Article  CAS  PubMed  Google Scholar 

  51. Böhm M, Mahfoud F, Ukena C, Bauer A, Fleck E, Hoppe UC, et al. Rationale and design of a large registry on renal denervation: the Global SYMPLICITY registry. EuroIntervention. 2013;9:484–92.

    Article  PubMed  Google Scholar 

  52. Bohm M. The global SYMPLICITY registry: safety and effectiveness of renal artery denervation in real world patients with uncontrolled hypertension. Washington, DC: American College of Cardiology Scientific Sessions; 2014.

    Google Scholar 

  53. Benamer H, Mylotte D, Garcia-Alonso C, Unterseeh T, Garot P, Louvard Y, et al. Renal denervation a treatment for resistant hypertension: a French experience. Ann Cardiol Angieol (Paris). 2013;62:384–91.

    Article  CAS  Google Scholar 

  54. Bhatt DL, Bakris GL. The promise of renal denervation. Cleve Clin J Med. 2012;79:498–500.

    Article  PubMed  Google Scholar 

  55. Persu A, Renkin J, Asayama K, O’Brien E, Staessen J. Renal denervation in treatment-resistant hypertension: the need for restraint and more and better evidence. Expert Rev Cardiovasc Ther. 2013;11:739–49.

    Article  CAS  PubMed  Google Scholar 

  56. Kandzari DE, Bhatt DL, Sobotka P, O’Neill WW, Esler M, Flack JM, et al. Catheter-based renal denervation for resistant hypertension: rationale and design of the SYMPLICITY HTN-3 trial. Clin Cardiol. 2012;35:528–35.

    Article  PubMed  Google Scholar 

  57. Bhatt DL, Kandzari DE, O’Neill WW, D’Agostino R, Flack JM, Katzen BT, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370:1393–401.

    Article  CAS  PubMed  Google Scholar 

  58. Messerli F, Bangalore S. Renal denervation for resistant hypertension? N Engl J Med. 2014;370:1454–7.

    Article  CAS  PubMed  Google Scholar 

  59. Medtronic. Medtronic completes first-in-man study for investigational next-generation multi-electrode renal denervation system in patients with treatment-resistant hypertension [Internet]. 2012. Available from: http://newsroom.medtronic.com/phoenix.zhtml?c=251324&p=irol-newsArticle&ID=1772019&highlight=.

  60. Whitbourn RJ, Harding S, Rothman MT, Walton T. TCT-491 renal artery denervation with a new simultaneous multielectrode catheter for treatment of resistant hypertension: results from the Symplicity Spyral(tm) first-in-man study. J Am Coll Cardiol. 2013;62:B150.

    Article  Google Scholar 

  61. Worthley S, Tsioufis C. Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: the EnligHTN I trial. Eur Heart J. 2013;34:2132–40.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Boston Scientific. Vessix global clinical program REDUCE HTN FIM and post market study [Internet]. 2014 [cited 2014 Mar 24]. Available from: http://www.bostonscientific.com/renal-denervation/Data_Cases/Clinical_Data/clinical-data.html.

  63. Mabin T, Sapoval M, Cabane V, Stemmett J, Iyer M. First experience with endovascular ultrasound renal denervation for the treatment of resistant hypertension. EuroIntervention. 2012;8:57–61.

    Article  PubMed  Google Scholar 

  64. Kona Medical. Clinical data reported for WAVE I and WAVE II studies of renal denervation therapy for hypertension at transcatheter cardiovascular therapeutics conference [Internet]. 2014 [cited 2014 Mar 25]. Available from: http://konamedical.com/renal-denervation-therapy-studies/.

  65. Neuzil P, Whitbourn RJ, Starek Z, Esler MD, Brinton T, Gertner M. TCT-61 optimized external focused ultrasound for renal sympathetic denervation – wave II trial. J Am Coll Cardiol. 2013;62:B20.

    Article  Google Scholar 

  66. Neuzil P, Petru J, Vondrakova D, Kopriva K, Chovanec M, Sediva L, et al. TCT-356 circumferential therapeutic ultrasound for the treatment of resistant hypertension: preliminary results of human feasibility study (SOUND-ITV). J Am Coll Cardiol. 2012;60:B101–2.

    Article  Google Scholar 

  67. Davis MI, Filion KB, Zhang D, Eisenberg MJ, Afilalo J, Schiffrin EL, et al. Effectiveness of renal denervation therapy for resistant hypertension: a systematic review and meta-analysis. J Am Coll Cardiol. 2013;62:231–41.

    Article  PubMed  Google Scholar 

  68. Howard JP, Nowbar AN, Francis DP. Size of blood pressure reduction from renal denervation: insights from meta-analysis of antihypertensive drug trials of 4,121 patients with focus on trial design: the CONVERGE report. Heart. 2013;99:1579–87.

    Article  PubMed  Google Scholar 

  69. Howard JP, Cole GD, Sievert H, Bhatt DL, Papademetriou V, Kandzari DE, et al. Unintentional overestimation of an expected antihypertensive effect in drug and device trials: mechanisms and solutions. Int J Cardiol. 2014;172:29–35.

    Article  PubMed  Google Scholar 

  70. Václavík J, Sedlák R, Plachy M, Navrátil K, Plásek J, Jarkovsky J, et al. Addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT): a randomized, double-blind, placebo-controlled trial. Hypertension. 2011;57:1069–75.

    Article  PubMed  Google Scholar 

  71. De Souza F, Muxfeldt E, Fiszman R, Salles G. Efficacy of spironolactone therapy in patients with true resistant hypertension. Hypertension. 2010;55:147–52.

    Article  PubMed  Google Scholar 

  72. Chapman N, Dobson J, Wilson S, Dahlöf B, Sever PS, Wedel H, et al. Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension. 2007;49:839–45.

    Article  CAS  PubMed  Google Scholar 

  73. Calhoun DA, White WB. Effectiveness of the selective aldosterone blocker, eplerenone, in patients with resistant hypertension. J Am Soc Hypertens. 2008;2:462–8. American Society of Hypertension.

    Article  PubMed  Google Scholar 

  74. Lane DA, Shah S, Beevers DG. Low-dose spironolactone in the management of resistant hypertension: a surveillance study. J Hypertens. 2007;25:891–4.

    Article  CAS  PubMed  Google Scholar 

  75. Corrao G, Nicotra F, Parodi A, Zambon A, Heiman F, Merlino L, et al. Cardiovascular protection by initial and subsequent combination of antihypertensive drugs in daily life practice. Hypertension. 2011;58:566–72.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Rayne Institute, British Heart Foundation Center of Research Excellence, St Thomas’ Hospital, King’s College London, 4th Floor, Lambeth Wing, Westminster Bridge Road, London, SE1 7EH, UK

    Aung Myat BSc (Hons), MBBS, MRCP

  2. Interventional Cardiovascular Programs, Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    Deepak L. Bhatt MD, MPH, FACC, FAHA, FSCAI, FESC

Authors
  1. Aung Myat BSc (Hons), MBBS, MRCP
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Deepak L. Bhatt MD, MPH, FACC, FAHA, FSCAI, FESC
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Deepak L. Bhatt MD, MPH, FACC, FAHA, FSCAI, FESC .

Editor information

Editors and Affiliations

  1. St. Luke's Medical Center, Phoenix, Arizona, USA

    Richard R. Heuser

  2. Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia

    Markus Schlaich

  3. CardioVascular Center Frankfurt Sankt Katharinen, Frankfurt, Germany

    Horst Sievert

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag London

About this chapter

Cite this chapter

Myat, A., Bhatt, D.L. (2015). Appraisal of the Clinical Trial Data on Renal Denervation for the Management of Resistant Hypertension. In: Heuser, R., Schlaich, M., Sievert, H. (eds) Renal Denervation. Springer, London. https://doi.org/10.1007/978-1-4471-5223-1_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-5223-1_5

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-5222-4

  • Online ISBN: 978-1-4471-5223-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation