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An Update on Treatment Options for Drug Resistant Hypertension

  • Hypertension (S Taler, Section Editor)
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Abstract

With the emergence of devices that can be used to intervene in patients’ drug resistant hypertension, the evaluation and management of this disorder has become more complex. There is little guidance for the management of drug resistant hypertension in existing guidelines due largely to an absence of clinical trials with hard cardiovascular outcomes; thus, most of the literature relies on short term (generally less than one year) studies that are oriented toward efficacy (i.e., blood pressure reduction, per se).

In this review we will cover newer developments in the field of drug resistant hypertension, particularly the use of device-based interventions and novel surgical procedures.

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References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 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. Circulation. 2008;117:e510–26.

    Article  PubMed  Google Scholar 

  2. Lynch AI, Irvin MR, Davis BR, Ford CE , Eckfeldt JH, Arnett DK. Genetic and Adverse Health Outcome Associations with Treatment Resistant Hypertension in GenHAT. Int J Hypertens. 2013; 578.

  3. Bangalore S, Fayyad R, Laskey R, Demicco DA. Prevalence, Predictors, and Outcomes in Treatment-resistant Hypertension in Patients with Coronary Disease. Am J Med. 2014;127:71–81.

    Article  PubMed  Google Scholar 

  4. Oliveras A, de la Sierra A. Resistant hypertension: patient characteristics, risk factors, co-morbidities and outcomes. J Hum Hypertens. 2013;28:213–7.

    Article  PubMed  Google Scholar 

  5. Smith SM. Epidemiology, prognosis, and treatment of resistant hypertension. Pharmacotherapy. 2013;33:1071–86.

    Article  PubMed  Google Scholar 

  6. Bangalore S, Fayyad R, Laskey R, Demicco D, Deedwania P, Kostis JB , et al. Lipid lowering in patients with treatment-resistant hypertension: an analysis from the Treating to New Targets (TNT) trial. Eur.Heart J. 2013; 1–8.

  7. Smith SM, Huo T, Delia Johnson B, Bittner V, Kelsey SF, Vido Thompson D, et al. Cardiovascular and Mortality Risk of Apparent Resistant Hypertension in Women With Suspected Myocardial Ischemia: A Report From the NHLBI-Sponsored WISE Study. J Am Heart Ass. 2014;3:e000660.

    Article  Google Scholar 

  8. Goodlad C, Unwin R, Reaich D,Cross J . Truly resistant hypertension? BMJ Case Rep. 2012

  9. Persell SD. Prevalence of resistant hypertension in the United States, 2003–2008. Hypertension. 2011;57:1076–80.

    Article  CAS  PubMed  Google Scholar 

  10. Galati S, Hopkins SM, Cheesman KC, Zhuk RA, Levine AC. Primary aldosteronism: emerging trends. Trends Endocrinol Met: TEM. 2013;24:421–30.

    Article  CAS  Google Scholar 

  11. Rimoldi SF ,Scherrer U, Messerli FH. Secondary arterial hypertension: when, who, and how to screen? Eur.Heart J. 2013; 1–12.

  12. De Nicola L, Gabbai FB, Agarwal R, Chiodini P, Borrelli S, Bellizzi V, et al. Prevalence and prognostic role of resistant hypertension in chronic kidney disease patients. JAmCollCardiol. 2013;61:2461–7.

    Article  PubMed  Google Scholar 

  13. Jung O, Gechter JL, Wunder C, Paulke A, Bartel C, Geiger H, et al. Resistant hypertension? Assessment of adherence by toxicological urine analysis. JHypertens. 2013;31:766–74. This European study demonstrated a disturbing prevalence of either no drug usage, or the presence of antihypertensive medications much less than anticipated. It raised serious issues about the role of non-adherence in drug resistant hypertension.

    Article  CAS  PubMed  Google Scholar 

  14. Fung V, Huang J, Brand R, Newhouse JP, Hsu J. Hypertension treatment in a medicare population: adherence and systolic blood pressure control. Clin Ther. 2007;29:972–84.

    Article  PubMed  Google Scholar 

  15. Fadl EM, 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.

  16. Ruzicka M, McCormick B, Leenen FHH, Froeschl M, Hiremath S. Adherence to blood pressure-lowering drugs and resistant hypertension: should trial of direct observation therapy be part of preassessment for renal denervation? Can J Cardiol. 2013;29:1741.

    Article  PubMed  Google Scholar 

  17. de la Sierra A. Profile of ambulatory blood pressure in resistant hypertension. Hypertens Res. 2013;36:565–9.

    Article  PubMed  Google Scholar 

  18. 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 Hypertens. 2014;32:3–15.

    Article  CAS  PubMed  Google Scholar 

  19. Harris SH. Renal Sympathectomy: Its Scope and Limitations. ProcRSocMed. 1935;28:1497–510.

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Smithwick RH, Thompson JE. Splanchnicectomy for essential hypertension; results in 1,266 cases. JAMA. 1953;152:1501–4.

    Article  CAS  Google Scholar 

  21. Gulati V, White WB. Review of the state of renal nerve ablation for patients with severe and resistant hypertension. J Am Soc Hypertens. 2013;7:484–93.

    Article  PubMed  Google Scholar 

  22. Leong KTG, Walton A, Krum H. Renal sympathetic denervation for the treatment of refractory hypertension. Annu Rev Med. 2014;65:349–65.

    Article  CAS  PubMed  Google Scholar 

  23. Schlaich MP, Lambert E, Kaye DM, Krozowski Z, Campbell DJ, Lambert G, et al. Sympathetic augmentation in hypertension: role of nerve firing, norepinephrine reuptake, and Angiotensin neuromodulation. Hypertension. 2004;43:169–75.

    Article  CAS  PubMed  Google Scholar 

  24. 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;61:457–64.

    Article  CAS  PubMed  Google Scholar 

  25. Hart EC, McBryde FD, Burchell AE, Ratcliffe LEK, Stewart LQ, Baumbach A, et al. Translational examination of changes in baroreflex function after renal denervation in hypertensive rats and humans. Hypertension. 2013;62:533–41.

    Article  CAS  PubMed  Google Scholar 

  26. Das UN. Renal sympathetic denervation for resistant hypertension–an alternate view. Med Hypotheses. 2013;81:1135–6.

    Article  PubMed  Google Scholar 

  27. Linz D, Mahfoud F, Schotten U, Ukena C, Hohl M, Neuberger H, et al. Renal sympathetic denervation provides ventricular rate control but does not prevent atrial electrical remodeling during atrial fibrillation. Hypertension. 2013;61:225–31.

    Article  CAS  PubMed  Google Scholar 

  28. Templin C, Jaguszewski M, Ghadri JR, Sudano I, Gaehwiler R, Hellermann JP, et al. Vascular lesions induced by renal nerve ablation as assessed by optical coherence tomography: pre- and post-procedural comparison with the Simplicity catheter system and the EnligHTN multi-electrode renal denervation catheter. EurHeart J. 2013;34:2141–8. 2148b.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Shah S, Jimenez MA, Fishel RS. Irrigated radiofrequency ablation catheter and electro-anatomical mapping with computerized tomography integration for renal artery sympathetic denervation. J Invasive Cardiol. 2012;24:308–10.

    Google Scholar 

  30. Zaman S, Pouliopoulos J, Al Raisi S, Sullivan J, Thiagalingam A, Swinnen J, et al. Novel use of NavX three-dimensional mapping to guide renal artery denervation. EuroIntervention. 2013;9:687–93.

    PubMed  Google Scholar 

  31. Ribichini F,Pighi M,Zivelonghi C ,Gambaro A,Valvo E,Lupo A, et al. Invasive assessment of renal artery atherosclerotic disease and resistant hypertension before renal sympathetic denervation. J.Nephrol. 26 799–801.

  32. Gosain P, Garimella PS, Hart PD, Agarwal R. Renal sympathetic denervation for treatment of resistant hypertension: a systematic review. J Clin Hypertens. 2013;15:75–84.

    Article  Google Scholar 

  33. 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. NEnglJMed. 2014. doi:10.1056/NEJMoa1402670.

    Google Scholar 

  34. 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 

  35. Davis MI, Filion KB, Eisenberg MJ, Afilalo J, Schiffrin EL, Joyal D. Reply: no support for renal denervation in a meta-analysis. J Am Coll Cardiol. 2013;62:2030.

    Article  PubMed  Google Scholar 

  36. Jin Y, Thijs L, Persu A, Kjeldsen S, Staessen JA. No support for renal denervation in a meta-analysis. J Am Coll Cardiol. 2013;62:2029–30.

    Article  PubMed  Google Scholar 

  37. Lambert T, Nahler A, Leisch F. Redo of percutaneous renal denervation in a patient with recurrent resistant hypertension after primary treatment success. Catheter Cardiovasc Interv. 2013;81:255–8.

    Article  Google Scholar 

  38. Ukena C, Mahfoud F, Ewen S, Cremers B, Laufs U, Bohm M. Renal denervation in the treatment of hypertension. Curr Hypertens Rep. 2013;15:363–9.

    Article  CAS  PubMed  Google Scholar 

  39. 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;35:528–35.

    Article  PubMed  Google Scholar 

  40. Kostka-Jeziorny K, Radziemski A, Tykarski A, Grajek S. Transient renal artery stenosis during renal sympathetic denervation in a patient with resistant hypertension. Kardiol Pol. 2013;71:776.

    Article  PubMed  Google Scholar 

  41. 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 

  42. Lenski M, Mahfoud F, Razouk A, Ukena C, Lenski D, Barth C, et al. Orthostatic function after renal sympathetic denervation in patients with resistant hypertension. Int J Cardiol. 2013;169:418–24.

    Article  PubMed  Google Scholar 

  43. Pansieri M, Barnay P, Larderet E, Krebs G, Aboukhoudir F, Andrieu S, et al. Renal denervation for resistant hypertension without general anesthesia: advantage of a MEOPA Morphin protocol. Preliminary experience. Ann Cardiol Angeiol. 2013;62:283–6.

    Article  CAS  Google Scholar 

  44. Barbash IM, Waksman R. Sympathetic renal denervation: hypertension beyond SYMPLICITY. Cardiovasc Revascularization Med. 2013;14:229–35.

    Article  Google Scholar 

  45. Worthley SG, Tsioufis CP, Worthley MI, Sinhal A, Chew DP, Meredith IT, et al. 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 

  46. Stabile E, Ambrosini V, Squarcia R, Salemme L, Popusoi G, Esposito G, et al. Percutaneous sympathectomy of the renal arteries: the OneShot Renal Denervation System is not associated with significant vessel wall injury. EuroIntervention. 2013;9:694–9.

    PubMed  Google Scholar 

  47. Honarvar M, Amirpour A, Pourmoghaddas M. Renal ablation for treatment of hypertension without Symplicity catheter: The first human experience. ARYA Atherosclerosis. 2013;9:82–8.

    PubMed Central  PubMed  Google Scholar 

  48. Patel HC, Dhillon PS, Mahfoud F, Lindsay AC, Hayward C, Ernst S, et al. The biophysics of renal sympathetic denervation using radiofrequency energy. Clinical research in cardiology. (2013). 2013 Sep 28. [Epub ahead of print].

  49. 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 

  50. Waksman R, Barbash IM, Chan R, Randolph P, Makuria AT, Virmani R. Beta radiation for renal nerve denervation: initial feasibility and safety. EuroIntervention. 2013;9:738–44.

    Article  PubMed  Google Scholar 

  51. Prochnau D, Figulla HR, Surber R. Cryoenergy is effective in the treatment of resistant hypertension in non-responders to radiofrequency renal denervation. Int J Cardiol. 2013;167:588–90.

    Article  PubMed  Google Scholar 

  52. Streitparth F, Gebauer B, Nickel P, Reinke P, Freyhardt P, Wieners G, et al. Percutaneous computer tomography-guided ethanol sympathicolysis for the treatment of resistant arterial hypertension. Cardiovasc Intervent Radiol. 2014;37:513–8.

    Article  CAS  PubMed  Google Scholar 

  53. Stefanadis C, Toutouzas K, Vlachopoulos C, Tsioufis C, Synetos A, Pietri P, et al. Chemical denervation of the renal artery with vincristine for the treatment of resistant arterial hypertension: first-in-man application. Hell J Cardiol. 2013;54:318–21.

    Google Scholar 

  54. Manning PT, Powers CW, Schmidt RE, Johnson EM. Guanethidine-induced destruction of peripheral sympathetic neurons occurs by an immune-mediated mechanism. J nEurosci: Off j Soc Neurosci. 1983;3:714–24.

    CAS  Google Scholar 

  55. Ott C, Schmid A, Ditting T, Sobotka PA, Veelken R, Uder M, et al. Renal denervation in a hypertensive patient with end-stage renal disease and small arteries: a direction for future research. J Clin Hypertens. 2012;14:799–801.

    Article  Google Scholar 

  56. Armaganijan L, Staico R, Abizaid A, Moraes A, Moreira D, Amodeo C, et al. Unilateral renal artery sympathetic denervation may reduce blood pressure in patients with resistant hypertension. J Clin Hypertens. 2013;15:606.

    Article  Google Scholar 

  57. Schroeter MR, Koziolek M. Early reduction of therapy-resistant hypertension in a patient after single-sided renal denervation approach. Clin Res Cardiol. 2014;103:79–81.

    Article  PubMed  Google Scholar 

  58. de Araujo Goncalves P, Teles RC, Raposo L. Catheter-based renal denervation for resistant hypertension performed by radial access. JInvasive Cardiol. 2013;25:147–9.

    PubMed  Google Scholar 

  59. Heuser RR, Mhatre AU, Buelna TJ, Berci WL, Hubbard BS. A novel non-vascular system to treat resistant hypertension. EuroIntervention. 2013;9:135–9.

    Article  PubMed  Google Scholar 

  60. Briasoulis A, Bakris GL. Timing and efficacy of alternative methods of sympathetic blockade. Curr Hypertens Rep. 2012;14:455–61.

    Article  CAS  PubMed  Google Scholar 

  61. Gronda E,Lovett EG,Tarascio M, Georgakopoulos D, Grassi G,Vanoli E. The Baroreceptor as a Therapeutic Target for Heart Failure. J Cardiovasc Transl Res. (2014).

  62. Gassler JP, Bisognano JD. Baroreflex activation therapy in hypertension. J. Hum. Hypertens. (2014) 1–6.

  63. Scheffers IJM, Kroon AA, Schmidli J, Jordan J, Tordoir JJM, Mohaupt MG, et al. Novel baroreflex activation therapy in resistant hypertension: results of a European multi-center feasibility study. J Am Coll Cardiol. 2010;56:1254–8.

    Article  PubMed  Google Scholar 

  64. Bisognano JD, Bakris G, Nadim MK, Sanchez L, Kroon AA, Schafer J, et al. Baroreflex activation therapy lowers blood pressure in patients with resistant hypertension: results from the double-blind, randomized, placebo-controlled rheos pivotal trial. J Am Coll Cardiol. 2011;58:765–73.

    Article  PubMed  Google Scholar 

  65. Bakris GL, Nadim MK, Haller H, Lovett EG, Schafer JE, Bisognano JD. Baroreflex activation therapy provides durable benefit in patients with resistant hypertension: results of long-term follow-up in the Rheos Pivotal Trial. J Am Soc Hypertens. 2012;6:152–8.

    Article  PubMed  Google Scholar 

  66. Alnima T, de Leeuw PW, Tan FES, Kroon AA. Renal responses to long-term carotid baroreflex activation therapy in patients with drug-resistant hypertension. Hypertension. 2013;61:1334–9.

    Article  CAS  PubMed  Google Scholar 

  67. Hoppe UC, Brandt M, Wachter R, Beige J, Rump LC, Kroon AA, et al. Minimally invasive system for baroreflex activation therapy chronically lowers blood pressure with pacemaker-like safety profile: results from the Barostim neo trial. J Am Soc Hypertens. 2012;6:270–6.

    Article  PubMed  Google Scholar 

  68. Logan AG, Perlikowski SM, Mente A, Tisler A, Tkacova R, Niroumand M, et al. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens. 2001;19:2271–7.

    Article  CAS  PubMed  Google Scholar 

  69. Marin JM, Agusti A, Villar I, Forner M, Nieto D, Carrizo SJ, et al. Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA. 2012;307:2169–76.

    Article  CAS  PubMed  Google Scholar 

  70. Marcus JA, Pothineni A, Marcus CZ, Bisognano JD. The role of obesity and obstructive sleep apnea in the pathogenesis and treatment of resistant hypertension. Curr Hypertens Rep. 2014;16:411.

    Article  PubMed  Google Scholar 

  71. Hubens LEG, Verloop WL, Joles JA, Blankestijn PJ, Voskuil M. Ischemia and reactive oxygen species in sympathetic hyperactivity states: a vicious cycle that can be interrupted by renal denervation? Curr Hypertens Rep. 2013;15:313–20.

    Article  CAS  PubMed  Google Scholar 

  72. Gonzaga CC, Gaddam KK, Ahmed MI, Pimenta E, Thomas SJ, Harding SM, et al. Severity of obstructive sleep apnea is related to aldosterone status in subjects with resistant hypertension. J Clin Sleep Med. 2010;6:363–8.

    PubMed Central  PubMed  Google Scholar 

  73. Gaddam K, Pimenta E, Thomas SJ, Cofield SS, Oparil S, Harding SM, et al. Spironolactone reduces severity of obstructive sleep apnoea in patients with resistant hypertension: a preliminary report. J Hum Hypertens. 2010;24:532–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  74. Bruno RM, Palagini L, Gemignani A, Virdis A, Di Giulio A, Ghiadoni L, et al. Poor Sleep Qual Resistant Hypertens. Sleep Med. 2013;14:1157–63.

    Article  PubMed  Google Scholar 

  75. Lozano L, Tovar JL, Sampol G, Romero O, Jurado MJ, Segarra A, et al. Continuous positive airway pressure treatment in sleep apnea patients with resistant hypertension: a randomized, controlled trial. J Hypertens. 2010;28:2161–8.

    Article  CAS  PubMed  Google Scholar 

  76. Martinez-Garcia M, Capote F, Campos-Rodriguez F, Lloberes P, de Atauri MJ D, Somoza M, et al. Effect of CPAP on blood pressure in patients with obstructive sleep apnea and resistant hypertension: the HIPARCO randomized clinical trial. JAMA. 2013;310:2407–15.

    CAS  PubMed  Google Scholar 

  77. Pedrosa RP, Drager LF, de Paula LKG, Amaro ACS, Bortolotto LA, Lorenzi-Filho G. Effects of OSA treatment on BP in patients with resistant hypertension: a randomized trial. Chest. 2013;144:1487–94.

    Article  CAS  PubMed  Google Scholar 

  78. Egan BM, Basile JN, Rehman SU, Davis PB, Grob CH, Riehle JF, et al. Plasma Renin test-guided drug treatment algorithm for correcting patients with treated but uncontrolled hypertension: a randomized controlled trial. Am J Hypertens. 2009;22:792–801.

    Article  CAS  PubMed  Google Scholar 

  79. Acelajado MC, Calhoun DA. Resistant hypertension, secondary hypertension, and hypertensive crises: diagnostic evaluation and treatment. Cardiol Clin. 2010;28:639–54.

    Article  PubMed  Google Scholar 

  80. Nishizaka M, Zaman MA, Calhoun DA. Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am J Hypertens. 2003;16:925–30.

    Article  CAS  PubMed  Google Scholar 

  81. Gaddam KK, Nishizaka MK, Pratt-Ubunama MN, Pimenta E, Aban I, Oparil S, et al. Characterization of resistant hypertension: association between resistant hypertension, aldosterone, and persistent intravascular volume expansion. Arch Intern Med. 2008;168:1159–64.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Chapman N, Dobson J, Wilson S, Dahlof 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 

  83. Ouzan J, Perault C, Lincoff AM, Carre E, Mertes M. The role of spironolactone in the treatment of patients with refractory hypertension. Am J Hypertens. 2002;15:333–9.

    Article  CAS  PubMed  Google Scholar 

  84. 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 

  85. Funder JW. Mineralocorticoid receptor antagonists: emerging roles in cardiovascular medicine. Integ Blood Press Control. 2013;6:129–38.

    Article  CAS  Google Scholar 

  86. Guichard JL, Clark D, Calhoun DA, Ahmed MI. Aldosterone receptor antagonists: current perspectives and therapies. Vasc Health and Risk Manag. 2013;9:321–31.

    CAS  Google Scholar 

  87. Krieger EM, Drager LF, Giorgi DMA, Krieger JE, Pereira AC, Barreto-Filho JAS, et al. Resistant hypertension optimal treatment trial: a randomized controlled trial. Clin Cardiol. 2014;37:1–6.

    Article  PubMed  Google Scholar 

  88. Yoshitomi Y, Kawanishi K, Yamaguchi A, Sakurai S, Minai K, Ishii T, et al. Effectiveness of the direct renin inhibitor, aliskiren, in patients with resistant hypertension. Int Heart J. 2013;54:88–92.

    Article  CAS  PubMed  Google Scholar 

  89. Shimosawa T. Salt, the renin-angiotensin-aldosterone system and resistant hypertension. Hypertens Res. 2013;36:657–60.

    Article  CAS  PubMed  Google Scholar 

  90. Bomback AS, Klemmer PJ. The incidence and implications of aldosterone breakthrough. Nat Clin Pract Nephrol. 2007;3:486–92.

    Article  CAS  PubMed  Google Scholar 

  91. Fontana V, de Faria APC ,Barbaro NR, Sabbatini AR , Modolo R , Lacchini R, et al. Modulation of aldosterone levels by −344 C/T CYP11B2 polymorphism and spironolactone use in resistant hypertension. Journal of the American Society of Hypertension. (2013) 1–6.

  92. Monge M, Lorthioir A, Bobrie G, Azizi M. New drug therapies interfering with the renin-angiotensin-aldosterone system for resistant hypertension. J Renin-Angiotensin-Aldosterone Syst. 2013;14:285–9.

    Article  PubMed  Google Scholar 

  93. Moorhouse RC, Webb DJ, Kluth DC, Dhaun N. Endothelin antagonism and its role in the treatment of hypertension. Curr Hypertens Rep. 2013;15:489–96.

    Article  CAS  PubMed  Google Scholar 

  94. Bakris GL, Lindholm LH, Black HR, Krum H, Linas S, Linseman JV, et al. Divergent results using clinic and ambulatory blood pressures: report of a darusentan-resistant hypertension trial. Hypertension. 2010;56:824–30.

    Article  CAS  PubMed  Google Scholar 

  95. Weber M, Black H, Bakris G, Krum H, Linas S, Weiss R, et al. A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;374:1423–31.

    Article  CAS  PubMed  Google Scholar 

  96. Webb DJ. DORADO: opportunity postponed: lessons from studies of endothelin receptor antagonists in treatment-resistant hypertension. Hypertension. 2010;56:806–7.

    Article  CAS  PubMed  Google Scholar 

  97. Black HR, Bakris GL, Weber MA, Weiss R, Shahawy ME, Marple R, et al. Efficacy and safety of darusentan in patients with resistant hypertension: results from a randomized, double-blind, placebo-controlled dose-ranging study. J Clin Hypertens. 2007;9:760–9.

    Article  CAS  Google Scholar 

  98. Spinasse LB, Santos AR, Suffys PN, Muxfeldt ES, Salles GF. Different phenotypes of the NAT2 gene influences hydralazine antihypertensive response in patients with resistant hypertension. Pharmacogenomics. 2014;15:169–78.

    Article  CAS  PubMed  Google Scholar 

  99. Jones ESW, Owen EP, Rayner BL. The association of the R563Q genotype of the ENaC with phenotypic variation in Southern Africa. Am J Hypertens. 2012;25:1286–91.

    CAS  PubMed  Google Scholar 

  100. Radtke J, Schmidt K, Wulff H, Kohler R. C de Wit. Activation of KCa3.1 by SKA-31 induces arteriolar dilatation and lowers blood pressure in normo- and hypertensive connexin40-deficient mice. Br J Pharmacol. 2013;170:293–303.

    Article  CAS  PubMed  Google Scholar 

  101. Boer-martins L, Figueiredo VN, Demacq C, Martins LC, Cabral AP , Faria D, et al. Original Article Leptin and Aldosterone in Sympathetic Activity in Resistant Hypertension with or without Type 2 Diabetes, (2012) 642–648.

  102. Appel LJ, Champagne CM, Harsha DW, Cooper LS, Obarzanek E, Elmer PJ, et al. Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial. JAMA. 2003;289:2083–93.

    PubMed  Google Scholar 

  103. Pimenta E, Gaddam KK, Oparil S, Aban I, Husain S, Dell'Italia LJ, et al. Effects of dietary sodium reduction on blood pressure in subjects with resistant hypertension: results from a randomized trial. Hypertension. 2009;54:475–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  104. Dimeo F, Pagonas N, Seibert F, Arndt R, Zidek W, Westhoff TH. Aerobic exercise reduces blood pressure in resistant hypertension. Hypertension. 2012;60:653–8.

    Article  CAS  PubMed  Google Scholar 

  105. Brouwers S, Schoors D, Dupont A, Dolan A, Dolan E, Celli B, et al. Iliofemoral Arteriovenous Fistula Decreases Blood Pressure in Severe COPD Patients with Hypertension. J Hypertens. 2012;30:e232.

    Article  Google Scholar 

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Conflict of Interest

Raymond Townsend is a board member for Medtronic. Townsend is a consultant for Janssen, Novartis, Glaxo SmithKline and Merck. Townsend received a grant from the NIH; received honoraria from the University of Tennessee and the University of Rochester; royalties from UpToDate and Jones & Bartlett; and received travel stipends from ASN, NKF, AHA and ASH. George Maliha has no conflicts of interest.

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Correspondence to Raymond R. Townsend.

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This article is part of the Topical Collection on Hypertension

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Maliha, G., Townsend, R.R. An Update on Treatment Options for Drug Resistant Hypertension. Curr Cardiovasc Risk Rep 8, 394 (2014). https://doi.org/10.1007/s12170-014-0394-5

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