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Published in: Current Treatment Options in Cardiovascular Medicine 12/2014

01-12-2014 | Prevention (L Sperling and D Gaita, Section Editors)

Renal Denervation Therapy for Resistant Hypertension

Authors: Mark Davis, MD, Ernesto L. Schiffrin, MD, PhD, Dominique Joyal, MD

Published in: Current Treatment Options in Cardiovascular Medicine | Issue 12/2014

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Opinion statement

Hypertension is common and leads to significant cardiovascular morbidity and mortality. Some patients are unable to achieve target blood pressures despite multiple antihypertensive medications; these patients are labeled as having resistant hypertension. To palliate the lack of pharmacologic options, recent technological advances led to the development of an interventional procedure to treat hypertension, namely renal sympathetic denervation. This percutaneous procedure involves the ablation of the afferent and efferent nerves surrounding the renal arteries. Many studies that were primarily observational in nature had very promising results. Systolic blood pressure reductions in the order of 25–30 mm Hg were observed in a series of unblinded studies, leading to the approval and widespread use of this technology across Europe, Australia, and Canada. However, a recent rigorous single blinded sham-controlled clinical trial failed to meet its efficacy endpoints. There are several postulated reasons for the conflicting results, which are discussed in this manuscript. These recent findings make us reflect on the need for rigorous clinical trials prior to the early approval and clinical adoption of novel technologies. At the moment, renal denervation remains an investigational procedure. Several trials are underway using different technologies, which, upon completion, will clarify the proper role of renal denervation for the treatment of patients with resistant hypertension.
Literature
1.
go back to reference Staessen JA, Kuznetsova T, Stolarz K. Hypertension prevalence and stroke mortality across populations. JAMA. 2003;289(18):2420–2.PubMedCrossRef Staessen JA, Kuznetsova T, Stolarz K. Hypertension prevalence and stroke mortality across populations. JAMA. 2003;289(18):2420–2.PubMedCrossRef
2.
go back to reference Persu A, Jin Y, Azizi M, Baelen M, Volz S, Elvan A, et al. Blood pressure changes after renal denervation at 10 European expert centers. J Hum Hypertens. 2014;28:150–6.PubMedCrossRefPubMedCentral Persu A, Jin Y, Azizi M, Baelen M, Volz S, Elvan A, et al. Blood pressure changes after renal denervation at 10 European expert centers. J Hum Hypertens. 2014;28:150–6.PubMedCrossRefPubMedCentral
3.
go back to reference 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(5):898–902.PubMedCrossRef 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(5):898–902.PubMedCrossRef
4.
go back to reference Persell SD. Prevalence of resistant hypertension in the United States, 2003–2008. Hypertension. 2011;57(6):1076–80.PubMedCrossRef Persell SD. Prevalence of resistant hypertension in the United States, 2003–2008. Hypertension. 2011;57(6):1076–80.PubMedCrossRef
5.
go back to reference Roberie DR, Elliott WJ. What is the prevalence of resistant hypertension in the United States? Curr Opin Cardiol. 2012;27(4):386–91.PubMedCrossRef Roberie DR, Elliott WJ. What is the prevalence of resistant hypertension in the United States? Curr Opin Cardiol. 2012;27(4):386–91.PubMedCrossRef
6.
go back to reference Sarafidis PA, Bakris GL. Resistant hypertension: an overview of evaluation and treatment. J Am Coll Cardiol. 2008;52(22):1749–57.PubMedCrossRef Sarafidis PA, Bakris GL. Resistant hypertension: an overview of evaluation and treatment. J Am Coll Cardiol. 2008;52(22):1749–57.PubMedCrossRef
7.
go back to reference DiBona GF, Esler M. Translational medicine: the antihypertensive effect of renal denervation. Am J Physiol Regul Integr Comp Physiol. 2010;298(2):R245–53.PubMedCrossRef DiBona GF, Esler M. Translational medicine: the antihypertensive effect of renal denervation. Am J Physiol Regul Integr Comp Physiol. 2010;298(2):R245–53.PubMedCrossRef
8.
go back to reference DiBona GF, Kopp UC. Neural control of renal function. Physiol Rev. 1997;77(1):75–197.PubMed DiBona GF, Kopp UC. Neural control of renal function. Physiol Rev. 1997;77(1):75–197.PubMed
9.
go back to reference Hendel MD, Collister JP. Renal denervation attenualtes long-term hypertensive effects of angiotensin II in the rat. Clin Exp Pharmacol Physiol. 2006;33(12):1225–30.PubMedCrossRef Hendel MD, Collister JP. Renal denervation attenualtes long-term hypertensive effects of angiotensin II in the rat. Clin Exp Pharmacol Physiol. 2006;33(12):1225–30.PubMedCrossRef
10.
go back to reference Krum H, Schlaich M, Sobotka P, Scheffers I, Kroon AA, de Leeuw PW. Novel procedure- and device-based strategies in the management of systemic hypertension. Eur Heart J. 2011;32(5):537–44.PubMedCrossRef Krum H, Schlaich M, Sobotka P, Scheffers I, Kroon AA, de Leeuw PW. Novel procedure- and device-based strategies in the management of systemic hypertension. Eur Heart J. 2011;32(5):537–44.PubMedCrossRef
11.
go back to reference Symplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension. Hypertension. 2011;57(5):911–7.CrossRef Symplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension. Hypertension. 2011;57(5):911–7.CrossRef
12.
go back to reference Krum H, Schlaich M, Whitbourn R, Sobotka PA, 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(9671):1275–81.PubMedCrossRef Krum H, Schlaich M, Whitbourn R, Sobotka PA, 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(9671):1275–81.PubMedCrossRef
13.
go back to reference 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(3):231–41.PubMedCrossRef 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(3):231–41.PubMedCrossRef
14.
go back to reference Symplicity HTN-2 Investigators. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010;376(9756):1903–9.CrossRef Symplicity HTN-2 Investigators. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010;376(9756):1903–9.CrossRef
15.
go back to reference 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(25):2694–5.PubMedCrossRef 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(25):2694–5.PubMedCrossRef
16.
go back to reference Vonend O, Antoch G, Rump LC, Blondin D. Secondary rise in blood pressure after renal denervation. Lancet. 2012;380(9843):778.PubMedCrossRef Vonend O, Antoch G, Rump LC, Blondin D. Secondary rise in blood pressure after renal denervation. Lancet. 2012;380(9843):778.PubMedCrossRef
17.
go back to reference Esler MD, Krum H, Schlaich M, Schmieder RE, Bohm 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(25):2976–82.PubMedCrossRef Esler MD, Krum H, Schlaich M, Schmieder RE, Bohm 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(25):2976–82.PubMedCrossRef
18.
go back to reference Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Bohm M, et al. Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol. 2012;59(10):901–9.PubMedCrossRef Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Bohm M, et al. Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol. 2012;59(10):901–9.PubMedCrossRef
19.
go back to reference Pokushalov E, Romanov A, Corbucci G, Artyomenko S, Baranova V, Turov A, et al. A randomized comparison of pulmonary vein isolation with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension. J Am Coll Cardiol. 2012;60(13):1163–70.PubMedCrossRef Pokushalov E, Romanov A, Corbucci G, Artyomenko S, Baranova V, Turov A, et al. A randomized comparison of pulmonary vein isolation with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension. J Am Coll Cardiol. 2012;60(13):1163–70.PubMedCrossRef
20.
go back to reference Ukena C, Bauer A, Mahfoud F, Schreieck J, Neuberger HR, Eick C, et al. Renal sympathetic denervation for treatment of electrical storm: first-in-man experience. Clin Res Cardiol. 2012;101(1):63–7.PubMedCrossRef Ukena C, Bauer A, Mahfoud F, Schreieck J, Neuberger HR, Eick C, et al. Renal sympathetic denervation for treatment of electrical storm: first-in-man experience. Clin Res Cardiol. 2012;101(1):63–7.PubMedCrossRef
21.
go back to reference Brandt MC, Reda S, Mahfoud F, Lenski M, Bohm M, Hoppe UC. Effects of renal sympathetic denervation on arterial stiffness and central hemodynamics in patients with resistant hypertension. J Am Coll Cardiol. 2012;60(19):1956–65.PubMedCrossRef Brandt MC, Reda S, Mahfoud F, Lenski M, Bohm M, Hoppe UC. Effects of renal sympathetic denervation on arterial stiffness and central hemodynamics in patients with resistant hypertension. J Am Coll Cardiol. 2012;60(19):1956–65.PubMedCrossRef
22.
go back to reference Egan BM. Renal sympathetic denervation: a novel intervention for resistant hypertension, insulin resistance, and sleep apnea. Hypertension. 2011;58(4):542–3.PubMedCrossRefPubMedCentral Egan BM. Renal sympathetic denervation: a novel intervention for resistant hypertension, insulin resistance, and sleep apnea. Hypertension. 2011;58(4):542–3.PubMedCrossRefPubMedCentral
23.
go back to reference Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC, et al. Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study. Circulation. 2011;123(18):1940–6.PubMedCrossRef Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC, et al. Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study. Circulation. 2011;123(18):1940–6.PubMedCrossRef
24.
go back to reference Mabin T, Sapoval M, Cabane V, Stemmett J, Iyer M. First experience with endovascular ultrasound renal denervation for the treatment of resistant hypertension. EuroInterv. 2012;8(1):57–61.CrossRef Mabin T, Sapoval M, Cabane V, Stemmett J, Iyer M. First experience with endovascular ultrasound renal denervation for the treatment of resistant hypertension. EuroInterv. 2012;8(1):57–61.CrossRef
25.
go back to reference Hering D, Mahfoud F, Walton AS, Krum H, Lambert GW, Lambert EA, et al. Renal denervation in moderate to severe CKD. J Am Soc Nephrol. 2012;23(7):1250–7.PubMedCrossRefPubMedCentral Hering D, Mahfoud F, Walton AS, Krum H, Lambert GW, Lambert EA, et al. Renal denervation in moderate to severe CKD. J Am Soc Nephrol. 2012;23(7):1250–7.PubMedCrossRefPubMedCentral
26.
go back to reference Kaltenbach B, Franke J, Bertog SC, Steinberg DH, Hofmann I, Sievert H. Renal sympathetic denervation as second-line therapy in mild resistant hypertension: a pilot study. Catheter Cardiovasc Interv. 2013;81(2):335–9.PubMedCrossRef Kaltenbach B, Franke J, Bertog SC, Steinberg DH, Hofmann I, Sievert H. Renal sympathetic denervation as second-line therapy in mild resistant hypertension: a pilot study. Catheter Cardiovasc Interv. 2013;81(2):335–9.PubMedCrossRef
27.
go back to reference Ahmed H, Neuzil P, Skoda J, Petru J, Sediva L, Schejbalova M, et al. Renal sympathetic denervation using an irrigated radiofrequency ablation catheter for the management of drug-resistant hypertension. JACC Cardiovasc Interv. 2012;5(7):758–65.PubMedCrossRef Ahmed H, Neuzil P, Skoda J, Petru J, Sediva L, Schejbalova M, et al. Renal sympathetic denervation using an irrigated radiofrequency ablation catheter for the management of drug-resistant hypertension. JACC Cardiovasc Interv. 2012;5(7):758–65.PubMedCrossRef
28.
go back to reference Prochnau D, Figulla HR, Surber R. Efficacy of renal denervation with a standard EP catheter in the 24-h ambulatory blood pressure monitoring-long-term follow-up. Int J Cardiol. 2012;157(3):447–8.PubMedCrossRef Prochnau D, Figulla HR, Surber R. Efficacy of renal denervation with a standard EP catheter in the 24-h ambulatory blood pressure monitoring-long-term follow-up. Int J Cardiol. 2012;157(3):447–8.PubMedCrossRef
29.
go back to reference Ukena C, Mahfoud F, Spies A, Kindermann I, Linz D, Cremers B, et al. Effects of renal sympathetic denervation on heart rate and atrioventricular conduction in patients with resistant hypertension. Int J Cardiol. 2013;167(6):2846–51.PubMedCrossRef Ukena C, Mahfoud F, Spies A, Kindermann I, Linz D, Cremers B, et al. Effects of renal sympathetic denervation on heart rate and atrioventricular conduction in patients with resistant hypertension. Int J Cardiol. 2013;167(6):2846–51.PubMedCrossRef
30.
go back to reference Witkowski A, Prejbisz A, Florczak E, Kadziela J, Sliwinski P, Bielen P, et al. Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea. Hypertension. 2011;58(4):559–65.PubMedCrossRef Witkowski A, Prejbisz A, Florczak E, Kadziela J, Sliwinski P, Bielen P, et al. Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea. Hypertension. 2011;58(4):559–65.PubMedCrossRef
31.
go back to reference Zuern CS, Rizas KD, Eick C, Stoleriu C, Bunk L, Barthel P, et al. Effects of renal sympathetic denervation on 24-hour blood pressure variability. Front Physiol. 2012;3:134.PubMedCrossRefPubMedCentral Zuern CS, Rizas KD, Eick C, Stoleriu C, Bunk L, Barthel P, et al. Effects of renal sympathetic denervation on 24-hour blood pressure variability. Front Physiol. 2012;3:134.PubMedCrossRefPubMedCentral
32.
go back to reference Kandzari DE, Bhatt DL, Sobotka PA, 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(9):528–35.PubMedCrossRef Kandzari DE, Bhatt DL, Sobotka PA, 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(9):528–35.PubMedCrossRef
33.••
go back to reference 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. NEJM. 2014;370(15):1393–401. The SYMPLICITY HTN-3 trial is the most rigorously designed trial investigating renal denervation. No significant difference in decrease in blood pressure was seen between renal denervation and controls.PubMedCrossRef 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. NEJM. 2014;370(15):1393–401. The SYMPLICITY HTN-3 trial is the most rigorously designed trial investigating renal denervation. No significant difference in decrease in blood pressure was seen between renal denervation and controls.PubMedCrossRef
34.
go back to reference Dowson A, Mullen MJ, Peatfield R, Muir K, Khan AA, Wells C, et al. Migraine Intervention With STARFlex Technology (MIST) Trial: a prospective, multicenter, double-blind, sham-controlled trial to evaluate the effectiveness of patent foramen ovale closure with STARFlex septal repair implant to resolve refractory nigraine headache. Circulation. 2008;117(11):1397–404.PubMedCrossRef Dowson A, Mullen MJ, Peatfield R, Muir K, Khan AA, Wells C, et al. Migraine Intervention With STARFlex Technology (MIST) Trial: a prospective, multicenter, double-blind, sham-controlled trial to evaluate the effectiveness of patent foramen ovale closure with STARFlex septal repair implant to resolve refractory nigraine headache. Circulation. 2008;117(11):1397–404.PubMedCrossRef
35.
go back to reference Hering D, Lambert EA, Marusic P, Walton AS, Krum H, Lambert GW, et al. Substantial reduction in single sympathetic nerve firing after renal denervation in patients with resistant hypertension. Hypertension. 2013;61(2):457–64.PubMedCrossRef Hering D, Lambert EA, Marusic P, Walton AS, Krum H, Lambert GW, et al. Substantial reduction in single sympathetic nerve firing after renal denervation in patients with resistant hypertension. Hypertension. 2013;61(2):457–64.PubMedCrossRef
36.
go back to reference Hering D, Marusic P, Walton AS, Lambert EA, Krum H, Narkiewicz K, et al. Sustained sympathetic and blood pressure reduction 1 year after renal denervation in patients with resistant hypertension. Hypertension. 2014. doi:10.1161/hypertensionaha.113.03098.PubMed Hering D, Marusic P, Walton AS, Lambert EA, Krum H, Narkiewicz K, et al. Sustained sympathetic and blood pressure reduction 1 year after renal denervation in patients with resistant hypertension. Hypertension. 2014. doi:10.​1161/​hypertensionaha.​113.​03098.PubMed
37.
go back to reference Messerli FH, Bangalore S. Renal denervation for resistant hypertension? NEJM. 2014;370(15):1454–7.PubMedCrossRef Messerli FH, Bangalore S. Renal denervation for resistant hypertension? NEJM. 2014;370(15):1454–7.PubMedCrossRef
38.
go back to reference Persu A, O'Brien E, Verdecchia P. Use of ambulatory blood pressure measurement in the definition of resistant hypertension: a review of the evidence. Hypertens Res. 2014. doi:10.1038/hr.2014.83.PubMed Persu A, O'Brien E, Verdecchia P. Use of ambulatory blood pressure measurement in the definition of resistant hypertension: a review of the evidence. Hypertens Res. 2014. doi:10.​1038/​hr.​2014.​83.PubMed
39.
go back to reference Fadl Elmula FE, Hoffmann P, Larstorp AC, Fossum E, Brekke M, Kjeldsen SE, et al. Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension. Hypertension. 2014;63(5):991–9.PubMedCrossRef Fadl Elmula FE, Hoffmann P, Larstorp AC, Fossum E, Brekke M, Kjeldsen SE, et al. Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension. Hypertension. 2014;63(5):991–9.PubMedCrossRef
Metadata
Title
Renal Denervation Therapy for Resistant Hypertension
Authors
Mark Davis, MD
Ernesto L. Schiffrin, MD, PhD
Dominique Joyal, MD
Publication date
01-12-2014
Publisher
Springer US
Published in
Current Treatment Options in Cardiovascular Medicine / Issue 12/2014
Print ISSN: 1092-8464
Electronic ISSN: 1534-3189
DOI
https://doi.org/10.1007/s11936-014-0350-1

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