Mineralocorticoid Receptor Antagonists Therapy in Resistant Hypertension: Time to Implement Guidelines!

Frontiers in Cardiovascular Medicine

Volumn 2, Issue , 2015, Pages

  Maiolino, Giuseppe ^a   Azzolini, Matteo ^a   Rossi, Gian Paolo ^a  

^a UNIVERSITY OF PADOVA   (Italy)

Author keywords

mineralocorticoid receptor antagonists; pathogenesis; resistant hypertension; review; therapy

Indexed keywords

EID: 84978422376     PISSN: None     EISSN: 2297055X     Source Type: Journal    
DOI: 10.3389/fcvm.2015.00003     Document Type: Article

References (127)

1. Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988-2000. JAMA (2003) 290:199–206.10.1001/jama.290.2.19912851274
2. Lloyd-Jones DM, Evans JC, Larson MG, O’Donnell CJ, Roccella EJ, Levy D. Differential control of systolic and diastolic blood pressure: factors associated with lack of blood pressure control in the community. Hypertension (2000) 36:594–9.10.1161/01.HYP.36.4.59411040241
3. Weitzman D, Chodick G, Shalev V, Grossman C, Grossman E. Prevalence and factors associated with resistant hypertension in a large health maintenance organization in Israel. Hypertension (2014) 64:501–7.10.1161/HYPERTENSIONAHA.114.0371824958503
4. 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) 57:898–902.10.1161/HYPERTENSIONAHA.110.16894821444835
5. Pierdomenico SD, Lapenna D, Bucci A, Di Tommaso R, Di Mascio R, Manente BM, et al. Cardiovascular outcome in treated hypertensive patients with responder, masked, false resistant, and true resistant hypertension. Am J Hypertens (2005) 18:1422–8.10.1016/j.amjhyper.2005.03.11516280275
6. Egan BM, Zhao Y, Li J, Brzezinski WA, Todoran TM, Brook RD, et al. Prevalence of optimal treatment regimens in patients with apparent treatment-resistant hypertension based on office blood pressure in a community-based practice network. Hypertension (2013) 62:691–7.10.1161/HYPERTENSIONAHA.113.0144823918752
7. Tomaszewski M, White C, Patel P, Masca N, Damani R, Hepworth J, et al. High rates of non-adherence to antihypertensive treatment revealed by high-performance liquid chromatography-tandem mass spectrometry (HP LC-MS/MS) urine analysis. Heart (2014) 100:855–61.10.1136/heartjnl-2013-30506324694797
8. Jung O, Gechter JL, Wunder C, Paulke A, Bartel C, Geiger H, et al. Resistant hypertension? Assessment of adherence by toxicological urine analysis. J Hypertens (2013) 31:766–74.10.1097/HJH.0b013e32835e228623337469
9. Ceral J, Habrdova V, Vorisek V, Bima M, Pelouch R, Solar M. Difficult-to-control arterial hypertension or uncooperative patients? The assessment of serum antihypertensive drug levels to differentiate non-responsiveness from non-adherence to recommended therapy. Hypertens Res (2011) 34:87–90.10.1038/hr.2010.18320882030
10. Rossi GP, Seccia TM, Maniero C, Pessina AC. Drug-related hypertension and resistance to antihypertensive treatment: a call for action. J Hypertens (2011) 29:2295–309.10.1097/HJH.0b013e32834c465d22002334
11. Cuspidi C, Macca G, Sampieri L, Michev I, Salerno M, Fusi V, et al. High prevalence of cardiac and extracardiac target organ damage in refractory hypertension. J Hypertens (2001) 19:2063–70.10.1097/00004872-200111000-0001811677373
12. Muntner P, Davis BR, Cushman WC, Bangalore S, Calhoun DA, Pressel SL, et al. Treatment-resistant hypertension and the incidence of cardiovascular disease and end-stage renal disease: results from the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). Hypertension (2014) 64:1012–21.10.1161/HYPERTENSIONAHA.114.0385025259745
13. 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) 51:1403–19.10.1161/HYPERTENSIONAHA.108.189141
14. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al. 2013 ESH/ESC 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 (2013) 34:2159–219.10.1093/eurheartj/eht151
15. Krause T, Lovibond K, Caulfield M, McCormack T, Williams B, Guideline Development Group. Management of hypertension: summary of NICE guidance. BMJ (2011) 343:d4891.10.1136/bmj.d4891
16. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, et al. Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. National heart, lung, and blood institute, national high blood pressure education program coordinating committee. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension (2003) 42:1206–52.10.1161/01.HYP.0000107251.49515.c2
17. Graudal NA, Hubeck-Graudal T, Jurgens G. Effects of low-sodium diet vs. high-sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride (Cochrane Review). Am J Hypertens (2012) 25:1–15.10.1038/ajh.2011.21022068710
18. Blumenthal JA, Babyak MA, Hinderliter A, Watkins LL, Craighead L, Lin PH, et al. Effects of the DASH diet alone and in combination with exercise and weight loss on blood pressure and cardiovascular biomarkers in men and women with high blood pressure: the ENCORE study. Arch Intern Med (2010) 170:126–35.10.1001/archinternmed.2009.47020101007
19. Neter JE, Stam BE, Kok FJ, Grobbee DE, Geleijnse JM. Influence of weight reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension (2003) 42:878–84.10.1161/01.HYP.0000094221.86888.AE12975389
20. Cornelissen VA, Fagard RH. Effects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factors. Hypertension (2005) 46:667–75.10.1161/01.HYP.0000184225.05629.5116157788
21. Cushman WC, Cutler JA, Hanna E, Bingham SF, Follmann D, Harford T, et al. Prevention and Treatment of Hypertension Study (PATHS): effects of an alcohol treatment program on blood pressure. Arch Intern Med (1998) 158:1197–207.10.1001/archinte.158.11.11979625399
22. Primatesta P, Falaschetti E, Gupta S, Marmot MG, Poulter NR. Association between smoking and blood pressure: evidence from the health survey for England. Hypertension (2001) 37:187–93.10.1161/01.HYP.37.2.18711230269
23. Messerli FH, Bangalore S. Treatment-resistant hypertension: another Cinderella story. Eur Heart J (2013) 34:1175–7.10.1093/eurheartj/eht028
24. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The antihypertensive and lipid-lowering treatment to prevent heart attack trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). JAMA (2002) 288:2981–97.10.1001/jama.288.23.2981
25. Gupta AK, Nasothimiou EG, Chang CL, Sever PS, Dahlof B, Poulter NR, et al. Baseline predictors of resistant hypertension in the Anglo-Scandinavian cardiac outcome trial (ASCOT): a risk score to identify those at high-risk. J Hypertens (2011) 29:2004–13.10.1097/HJH.0b013e32834a8a4221881528
26. Jamerson K, Weber MA, Bakris GL, Dahlof B, Pitt B, Shi V, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med (2008) 359:2417–28.10.1056/NEJMoa080618219052124
27. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, et al. Cardiovascular morbidity and mortality in the Losartan intervention for endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet (2002) 359:995–1003.10.1016/S0140-6736(02)08089-3
28. Pepine CJ, Handberg EM, Cooper-DeHoff RM, Marks RG, Kowey P, Messerli FH, et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. JAMA (2003) 290:2805–16.10.1001/jama.290.21.280514657064
29. Black HR, Elliott WJ, Grandits G, Grambsch P, Lucente T, White WB, et al. Principal results of the controlled onset verapamil investigation of cardiovascular end points (CONVINCE) trial. JAMA (2003) 289:2073–82.10.1001/jama.289.16.207312709465
30. Pimenta E, Calhoun DA. Resistant hypertension: incidence, prevalence, and prognosis. Circulation (2012) 125:1594–6.10.1161/CIRCULATIONAHA.112.097345
31. Persell SD. Prevalence of resistant hypertension in the United States, 2003-2008. Hypertension (2011) 57:1076–80.10.1161/HYPERTENSIONAHA.111.170308
32. 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) 125:1635–42.10.1161/CIRCULATIONAHA.111.06806422379110
33. Muxfeldt ES, Bloch KV, Nogueira Ada R, Salles GF. True resistant hypertension: is it possible to be recognized in the office? Am J Hypertens (2005) 18:1534–40.10.1016/j.amjhyper.2005.06.01316364821
34. de la Sierra A, Banegas JR, Oliveras A, Gorostidi M, Segura J, de la Cruz JJ, et al. Clinical differences between resistant hypertensives and patients treated and controlled with three or less drugs. J Hypertens (2012) 30:1211–6.10.1097/HJH.0b013e328353634e22525201
35. Oliveras A, Armario P, Hernandez-Del Rey R, Arroyo JA, Poch E, Larrousse M, et al. Urinary albumin excretion is associated with true resistant hypertension. J Hum Hypertens (2010) 24:27–33.10.1038/jhh.2009.3519421225
36. Oliveras A, Armario P, Martell-Claros N, Ruilope LM, de la Sierra A, Spanish Society of Hypertension-Resistant Hypertension Registry. Urinary albumin excretion is associated with nocturnal systolic blood pressure in resistant hypertensives. Hypertension (2011) 57:556–60.10.1161/HYPERTENSIONAHA.110.16556321220713
37. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet (2002) 360:1903–13.10.1016/S0140-6736(02)11911-812493255
38. Salles GF, Cardoso CR, Muxfeldt ES. Prognostic influence of office and ambulatory blood pressures in resistant hypertension. Arch Intern Med (2008) 168:2340–6.10.1001/archinte.168.21.234019029499
39. Kumbhani DJ, Steg PG, Cannon CP, Eagle KA, Smith SC, Jr Crowley K, et al. Resistant hypertension: a frequent and ominous finding among hypertensive patients with atherothrombosis. Eur Heart J (2013) 34:1204–14.10.1093/eurheartj/ehs36823144048
40. Banegas JR, Segura J, Ruilope LM, Luque M, Garcia-Robles R, Campo C, et al. Blood pressure control and physician management of hypertension in hospital hypertension units in Spain. Hypertension (2004) 43:1338–44.10.1161/01.HYP.0000127424.59774.8415117908
41. Banegas JR, Lundelin K, de la Figuera M, de la Cruz JJ, Graciani A, Rodriguez-Artalejo F, et al. Physician perception of blood pressure control and treatment behavior in high-risk hypertensive patients: a cross-sectional study. PLoS One (2011) 6:e24569.10.1371/journal.pone.002456921935425
42. Myat A, Redwood SR, Qureshi AC, Spertus JA, Williams B. Resistant hypertension. BMJ (2012) 345:e7473.10.1136/bmj.e7473
43. Umpierrez GE, Cantey P, Smiley D, Palacio A, Temponi D, Luster K, et al. Primary aldosteronism in diabetic subjects with resistant hypertension. Diabetes Care (2007) 30:1699–703.10.2337/dc07-003117429062
44. Sang X, Jiang Y, Wang W, Yan L, Zhao J, Peng Y, et al. Prevalence of and risk factors for primary aldosteronism among patients with resistant hypertension in China. J Hypertens (2013) 31:1465–71.10.1097/HJH.0b013e328360ddf624006040
45. Pedrosa RP, Drager LF, Gonzaga CC, Sousa MG, de Paula LK, Amaro AC, et al. Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension. Hypertension (2011) 58:811–7.10.1161/HYPERTENSIONAHA.111.17978821968750
46. Benjamin MM, Fazel P, Filardo G, Choi JW, Stoler RC. Prevalence of and risk factors of renal artery stenosis in patients with resistant hypertension. Am J Cardiol (2014) 113:687–90.10.1016/j.amjcard.2013.10.04624342757
47. Midgley JP, Matthew AG, Greenwood CM, Logan AG. Effect of reduced dietary sodium on blood pressure: a meta-analysis of randomized controlled trials. JAMA (1996) 275:1590–7.10.1001/jama.275.20.15908622251
48. Calhoun DA, Nishizaka MK, Zaman MA, Thakkar RB, Weissmann P. Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension (2002) 40:892–6.10.1161/01.HYP.0000040261.30455.B612468575
49. Rossi GP, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C, et al. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol (2006) 48:2293–300.10.1016/j.jacc.2006.07.05917161262
50. Rossi GP. A comprehensive review of the clinical aspects of primary aldosteronism. Nat Rev Endocrinol (2011) 7:485–95.10.1038/nrendo.2011.7621610687
51. Bobrie G, Frank M, Azizi M, Peyrard S, Boutouyrie P, Chatellier G, et al. Sequential nephron blockade versus sequential renin-angiotensin system blockade in resistant hypertension: a prospective, randomized, open blinded endpoint study. J Hypertens (2012) 30:1656–64.10.1097/HJH.0b013e3283551e9822728905
52. Staessen J, Lijnen P, Fagard R, Verschueren LJ, Amery A. Rise in plasma concentration of aldosterone during long-term angiotensin II suppression. J Endocrinol (1981) 91:457–65.10.1677/joe.0.09104577035596
53. Schjoedt KJ, Andersen S, Rossing P, Tarnow L, Parving HH. Aldosterone escape during blockade of the renin-angiotensin-aldosterone system in diabetic nephropathy is associated with enhanced decline in glomerular filtration rate. Diabetologia (2004) 47:1936–9.10.1007/s00125-004-1542-015551047
54. Bomback AS, Klemmer PJ. The incidence and implications of aldosterone breakthrough. Nat Clin Pract Nephrol (2007) 3:486–92.10.1038/ncpneph057517717561
55. Levy DG, Rocha R, Funder JW. Distinguishing the antihypertensive and electrolyte effects of eplerenone. J Clin Endocrinol Metab (2004) 89:2736–40.10.1210/jc.2003-03214915181050
56. Gomez-Sanchez EP. Intracerebroventricular infusion of aldosterone induces hypertension in rats. Endocrinology (1986) 118:819–23.10.1210/endo-118-2-8193943493
57. Farquharson CA, Struthers AD. Aldosterone induces acute endothelial dysfunction in vivo in humans: evidence for an aldosterone-induced vasculopathy. Clin Sci (Lond) (2002) 103:425–31.12241543
58. Romagni P, Rossi F, Guerrini L, Quirini C, Santiemma V. Aldosterone induces contraction of the resistance arteries in man. Atherosclerosis (2003) 166:345–9.10.1016/S0021-9150(02)00363-512535748
59. McCurley A, Pires PW, Bender SB, Aronovitz M, Zhao MJ, Metzger D, et al. Direct regulation of blood pressure by smooth muscle cell mineralocorticoid receptors. Nat Med (2012) 18:1429–33.10.1038/nm.289122922412
60. Tu W, Eckert GJ, Hannon TS, Liu H, Pratt LM, Wagner MA, et al. Racial differences in sensitivity of blood pressure to aldosterone. Hypertension (2014) 63:1212–8.10.1161/HYPERTENSIONAHA.113.0298924711519
61. Funder JW. Sensitivity to aldosterone: plasma levels are not the full story. Hypertension (2014) 63:1168–70.10.1161/HYPERTENSIONAHA.114.03127
62. Shibata H, Itoh H. Mineralocorticoid receptor-associated hypertension and its organ damage: clinical relevance for resistant hypertension. Am J Hypertens (2012) 25:514–23.10.1038/ajh.2011.24522258336
63. AbdAlla S, Lother H, Quitterer U. AT1-receptor heterodimers show enhanced G-protein activation and altered receptor sequestration. Nature (2000) 407:94–8.10.1038/3502409510993080
64. Yamada M, Kushibiki M, Osanai T, Tomita H, Okumura K. Vasoconstrictor effect of aldosterone via angiotensin II type 1 (AT1) receptor: possible role of AT1 receptor dimerization. Cardiovasc Res (2008) 79:169–78.10.1093/cvr/cvn06418326554
65. Robert V, Heymes C, Silvestre JS, Sabri A, Swynghedauw B, Delcayre C. Angiotensin AT1 receptor subtype as a cardiac target of aldosterone: role in aldosterone-salt-induced fibrosis. Hypertension (1999) 33:981–6.10.1161/01.HYP.33.4.98110205234
66. Nishizaka MK, Pratt-Ubunama M, Zaman MA, Cofield S, Calhoun DA. Validity of plasma aldosterone-to-renin activity ratio in African American and white subjects with resistant hypertension. Am J Hypertens (2005) 18:805–12.10.1016/j.amjhyper.2005.01.00215925740
67. 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) 54:475–81.10.1161/HYPERTENSIONAHA.109.13123519620517
68. Graves JW, Bloomfield RL, Buckalew VM. Plasma volume in resistant hypertension: guide to pathophysiology and therapy. Am J Med Sci (1989) 298:361–5.10.1097/00000441-198912000-000012596494
69. 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) 168:1159–64.10.1001/archinte.168.11.115918541823
70. Taler SJ, Textor SC, Augustine JE. Resistant hypertension: comparing hemodynamic management to specialist care. Hypertension (2002) 39:982–8.10.1161/01.HYP.0000016176.16042.2F12019280
71. Labeit AM, Klotsche J, Pieper L, Pittrow D, Einsle F, Stalla GK, et al. Changes in the prevalence, treatment and control of hypertension in Germany? A clinical-epidemiological study of 50.000 primary care patients. PLoS One (2012) 7:e52229.10.1371/journal.pone.005222923284945
72. Esler M, Straznicky N, Eikelis N, Masuo K, Lambert G, Lambert E. Mechanisms of sympathetic activation in obesity-related hypertension. Hypertension (2006) 48:787–96.10.1161/01.HYP.0000242642.42177.49
73. Rossi GP, Belfiore A, Bernini G, Fabris B, Caridi G, Ferri C, et al. Body mass index predicts plasma aldosterone concentrations in overweight-obese primary hypertensive patients. J Clin Endocrinol Metab (2008) 93:2566–71.10.1210/jc.2008-025118445663
74. Lloberes P, Lozano L, Sampol G, Romero O, Jurado MJ, Rios J, et al. Obstructive sleep apnoea and 24-h blood pressure in patients with resistant hypertension. J Sleep Res (2010) 19:597–602.10.1111/j.1365-2869.2010.00839.x20545837
75. Goncalves SC, Martinez D, Gus M, de Abreu-Silva EO, Bertoluci C, Dutra I, et al. Obstructive sleep apnea and resistant hypertension: a case-control study. Chest (2007) 132:1858–62.10.1378/chest.07-117018079220
76. 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) 6:363–8.20726285
77. 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) 28:2161–8.10.1097/HJH.0b013e32833b9c6320577130
78. Parati G, Lombardi C, Hedner J, Bonsignore MR, Grote L, Tkacova R, et al. Position paper on the management of patients with obstructive sleep apnea and hypertension: joint recommendations by the European society of hypertension, by the European respiratory society and by the members of European Cost (cooperation in scientific and technological RESEARCH) ACTION B26 on obstructive sleep apnea. J Hypertens (2012) 30:633–46.10.1097/HJH.0b013e328350e53b22406463
79. 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) 24:532–7.10.1038/jhh.2009.9620016520
80. Mente A, O’Donnell MJ, Rangarajan S, McQueen MJ, Poirier P, Wielgosz A, et al. Association of urinary sodium and potassium excretion with blood pressure. N Engl J Med (2014) 371:601–11.10.1056/NEJMoa131198925119606
81. He FJ, MacGregor GA. Effect of modest salt reduction on blood pressure: a meta-analysis of randomized trials. Implications for public health. J Hum Hypertens (2002) 16:761–70.10.1038/sj.jhh.100145912444537
82. Dimeo F, Pagonas N, Seibert F, Arndt R, Zidek W, Westhoff TH. Aerobic exercise reduces blood pressure in resistant hypertension. Hypertension (2012) 60:653–8.10.1161/HYPERTENSIONAHA.111.00058
83. Law MR, Wald NJ, Morris JK, Jordan RE. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ (2003) 326:1427.10.1136/bmj.326.7404.142712829555
84. Wald DS, Law M, Morris JK, Bestwick JP, Wald NJ. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. Am J Med (2009) 122:290–300.10.1016/j.amjmed.2008.09.03819272490
85. Ogawa H, Kim-Mitsuyama S, Matsui K, Jinnouchi T, Jinnouchi H, Arakawa K, et al. Angiotensin II receptor blocker-based therapy in Japanese elderly, high-risk, hypertensive patients. Am J Med (2012) 125:981–90.10.1016/j.amjmed.2011.12.01022503610
86. Peterzan MA, Hardy R, Chaturvedi N, Hughes AD. Meta-analysis of dose-response relationships for hydrochlorothiazide, chlorthalidone, and bendroflumethiazide on blood pressure, serum potassium, and urate. Hypertension (2012) 59:1104–9.10.1161/HYPERTENSIONAHA.111.19063722547443
87. Messerli FH, Bangalore S. Antihypertensive efficacy of aliskiren: is hydrochlorothiazide an appropriate benchmark? Circulation (2009) 119:371–3.10.1161/CIRCULATIONAHA.108.828897
88. Messerli FH, Makani H, Benjo A, Romero J, Alviar C, Bangalore S. Antihypertensive efficacy of hydrochlorothiazide as evaluated by ambulatory blood pressure monitoring: a meta-analysis of randomized trials. J Am Coll Cardiol (2011) 57:590–600.10.1016/j.jacc.2010.07.05321272751
89. Gifford RW, Jr Kirkendall W, O’Connor DT, Weidman W. Office evaluation of hypertension. A statement for health professionals by a writing group of the council for high blood pressure research, American Heart Association. Circulation (1989) 79:721–31.10.1161/01.CIR.79.3.7212917396
90. 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) 58:765–73.10.1016/j.jacc.2011.06.00821816315
91. 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) 373:1275–81.10.1016/S0140-6736(09)60566-319332353
92. Symplicity HTN-2 Investigators Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (The symplicity HTN-2 Trial): a randomised controlled trial. Lancet (2010) 376:1903–9.10.1016/S0140-6736(10)62039-921093036
93. 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) 370:1393–401.10.1056/NEJMoa140267024678939
94. Rossi GP, Maiolino G. Mineralocorticoid receptor antagonism as an add-on treatment for resistant hypertension. Hypertens Res (2014) 37:1029–31.10.1038/hr.2014.139
95. Karlberg BE, Kagedal B, Tegler L, Tolagen K, Bergman B. Controlled treatment of primary hypertension with propranolol and spironolactone. A crossover study with special reference to initial plasma renin activity. Am J Cardiol (1976) 37:642–9.10.1016/0002-9149(76)90409-4769527
96. Ogilvie RI, Piafsky KM, Ruedy J. Antihypertensive responses to spironolactone in normal renin hypertension. Clin Pharmacol Ther (1978) 24:525–30.699476
97. Kreeft JH, Larochelle P, Ogilvie RI. Comparison of chlorthalidone and spironolactone in low – renin essential hypertension. Can Med Assoc J (1983) 128:31–4.6336600
98. Pratt JH, Eckert GJ, Newman S, Ambrosius WT. Blood pressure responses to small doses of amiloride and spironolactone in normotensive subjects. Hypertension (2001) 38:1124–9.10.1161/hy1101.09501011711509
99. Weinberger MH, Roniker B, Krause SL, Weiss RJ. Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension. Am J Hypertens (2002) 15:709–16.10.1016/S0895-7061(02)02957-612160194
100. Burgess ED, Lacourciere Y, Ruilope-Urioste LM, Oparil S, Kleiman JH, Krause S, et al. Long-term safety and efficacy of the selective aldosterone blocker eplerenone in patients with essential hypertension. Clin Ther (2003) 25:2388–404.10.1016/S0149-2918(03)80282-514604739
101. White WB, Carr AA, Krause S, Jordan R, Roniker B, Oigman W. Assessment of the novel selective aldosterone blocker eplerenone using ambulatory and clinical blood pressure in patients with systemic hypertension. Am J Cardiol (2003) 92:38–42.10.1016/S0002-9149(03)00461-212842242
102. Delyani JA. Mineralocorticoid receptor antagonists: the evolution of utility and pharmacology. Kidney Int (2000) 57:1408–11.10.1046/j.1523-1755.2000.00983.x10760075
103. Flack JM, Oparil S, Pratt JH, Roniker B, Garthwaite S, Kleiman JH, et al. Efficacy and tolerability of eplerenone and losartan in hypertensive black and white patients. J Am Coll Cardiol (2003) 41:1148–55.10.1016/S0735-1097(03)00054-812679215
104. Weinberger MH, White WB, Ruilope LM, MacDonald TM, Davidson RC, Roniker B, et al. Effects of eplerenone versus losartan in patients with low-renin hypertension. Am Heart J (2005) 150:426–33.10.1016/j.ahj.2004.12.00516169319
105. Williams GH, Burgess E, Kolloch RE, Ruilope LM, Niegowska J, Kipnes MS, et al. Efficacy of eplerenone versus enalapril as monotherapy in systemic hypertension. Am J Cardiol (2004) 93:990–6.10.1016/j.amjcard.2004.01.00715081441
106. Pitt B, Reichek N, Willenbrock R, Zannad F, Phillips RA, Roniker B, et al. Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation (2003) 108:1831–8.10.1161/01.CIR.0000091405.00772.6E14517164
107. White WB, Duprez D, St Hillaire R, Krause S, Roniker B, Kuse-Hamilton J, et al. Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. Hypertension (2003) 41:1021–6.10.1161/01.HYP.0000067463.13172.EA12682082
108. Krum H, Nolly H, Workman D, He W, Roniker B, Krause S, et al. Efficacy of eplerenone added to renin-angiotensin blockade in hypertensive patients. Hypertension (2002) 40:117–23.10.1161/01.HYP.0000025146.19104.FE12154100
109. Ando K, Ohtsu H, Uchida S, Kaname S, Arakawa Y, Fujita T, et al. Anti-albuminuric effect of the aldosterone blocker eplerenone in non-diabetic hypertensive patients with albuminuria: a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol (2014) 2:944–53.10.1016/S2213-8587(14)70194-925466242
110. 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) 15:333–9.10.1016/S0895-7061(01)02342-111991219
111. Nishizaka MK, Zaman MA, Calhoun DA. Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am J Hypertens (2003) 16:925–30.10.1016/S0895-7061(03)01032-X14573330
112. Sharabi Y, Adler E, Shamis A, Nussinovitch N, Markovitz A, Grossman E. Efficacy of add-on aldosterone receptor blocker in uncontrolled hypertension. Am J Hypertens (2006) 19:750–5.10.1016/j.amjhyper.2005.11.01616814132
113. Lane DA, Shah S, Beevers DG. Low-dose spironolactone in the management of resistant hypertension: a surveillance study. J Hypertens (2007) 25:891–4.10.1097/HJH.0b013e328014954d17351384
114. Saha C, Eckert GJ, Ambrosius WT, Chun TY, Wagner MA, Zhao Q, et al. Improvement in blood pressure with inhibition of the epithelial sodium channel in blacks with hypertension. Hypertension (2005) 46:481–7.10.1161/01.HYP.0000179582.42830.1d
115. 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) 49:839–45.10.1161/01.HYP.0000259805.18468.8c17309946
116. de Souza F, Muxfeldt E, Fiszman R, Salles G. Efficacy of spironolactone therapy in patients with true resistant hypertension. Hypertension (2010) 55:147–52.10.1161/HYPERTENSIONAHA.109.14098819858405
117. Colussi G, Catena C, Sechi LA. Spironolactone, eplerenone and the new aldosterone blockers in endocrine and primary hypertension. J Hypertens (2013) 31:3–15.10.1097/HJH.0b013e3283599b6a23011526
118. Marrs JC. Spironolactone management of resistant hypertension. Ann Pharmacother (2010) 44:1762–9.10.1345/aph.1P338
119. Vaclavik J, Sedlak R, Plachy M, Navratil K, Plasek J, Jarkovsky J, et al. Addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT): a randomized, double-blind, placebo-controlled trial. Hypertension (2011) 57:1069–75.10.1161/HYPERTENSIONAHA.111.16996121536989
120. Abolghasmi R, Taziki O. Efficacy of low dose spironolactone in chronic kidney disease with resistant hypertension. Saudi J Kidney Dis Transpl (2011) 22:75–8.21196617
121. Oxlund CS, Henriksen JE, Tarnow L, Schousboe K, Gram J, Jacobsen IA. Low dose spironolactone reduces blood pressure in patients with resistant hypertension and type 2 diabetes mellitus: a double blind randomized clinical trial. J Hypertens (2013) 31:2094–102.10.1097/HJH.0b013e3283638b1a24107738
122. Karns AD, Bral JM, Hartman D, Peppard T, Schumacher C. Study of aldosterone synthase inhibition as an add-on therapy in resistant hypertension. J Clin Hypertens (Greenwich) (2013) 15:186–92.10.1111/jch.1205123458591
123. Mahmud A, Mahgoub M, Hall M, Feely J. Does aldosterone-to-renin ratio predict the antihypertensive effect of the aldosterone antagonist spironolactone? Am J Hypertens (2005) 18:1631–5.10.1016/j.amjhyper.2005.06.01016364838
124. Shlomai G, Sella T, Sharabi Y, Leibowitz A, Grossman E. Serum potassium levels predict blood pressure response to aldosterone antagonists in resistant hypertension. Hypertens Res (2014) 37:1037–41.10.1038/hr.2014.7724671013
125. Prisant LM, Krum H, Roniker B, Krause SL, Fakouhi K, He W. Can renin status predict the antihypertensive efficacy of eplerenone add-on therapy? J Clin Pharmacol (2003) 43:1203–10.10.1177/009127000325818914551174
126. Parthasarathy HK, Alhashmi K, McMahon AD, Struthers AD, McInnes GT, Ford I, et al. Does the ratio of serum aldosterone to plasma renin activity predict the efficacy of diuretics in hypertension? Results of RENALDO. J Hypertens (2010) 28:170–7.10.1097/HJH.0b013e328332b79b20009770
127. Tan SY, Shapiro R, Franco R, Stockard H, Mulrow PJ. Indomethacin-induced prostaglandin inhibition with hyperkalemia. A reversible cause of hyporeninemic hypoaldosteronism. Ann Intern Med (1979) 90:783–5.10.7326/0003-4819-90-5-783434681