Drug therapy of apparent treatment-resistant hypertension: Focus on mineralocorticoid receptor antagonists

Drugs

Volumn 75, Issue 5, 2015, Pages 473-485

  Glicklich, Daniel ^a,b   Frishman, William H ^b  

^a WESTCHESTER MEDICAL CENTER   (United States)

^b NEW YORK MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOTENSIN RECEPTOR ANTAGONIST; ANTIHYPERTENSIVE AGENT; CALCIUM CHANNEL BLOCKING AGENT; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIURETIC AGENT; MINERALOCORTICOID ANTAGONIST;

ANIMAL; COMORBIDITY; DRUG COMBINATION; DRUG MONITORING; EVIDENCE BASED MEDICINE; HUMAN; HYPERTENSION; MULTIDRUG RESISTANCE; PRACTICE GUIDELINE;

ANGIOTENSIN RECEPTOR ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; ANIMALS; ANTIHYPERTENSIVE AGENTS; CALCIUM CHANNEL BLOCKERS; COMORBIDITY; DIURETICS; DRUG MONITORING; DRUG RESISTANCE, MULTIPLE; DRUG THERAPY, COMBINATION; EVIDENCE-BASED MEDICINE; HUMANS; HYPERTENSION; MINERALOCORTICOID RECEPTOR ANTAGONISTS; PRACTICE GUIDELINES AS TOPIC;

EID: 84937511858     PISSN: 00126667     EISSN: 11791950     Source Type: Journal    
DOI: 10.1007/s40265-015-0372-3     Document Type: Article

References (97)

1. Vemulapalli S, Ard J, Bakris GL, Bhatt DL, et al. Proceedings from Duke resistant hypertension think tank. Am Heart J. 2014;167:775-88. doi: 10.1016/j.ahj.2014.02.008.
2. Vega J, Bisognano JD. The prevalence, incidence, prognosis and associated conditions of resistant hypertension. Semin Nephrol. 2014;2014(34):247-56. doi: 10.1016/j.semnephrol.04.002.
3. Krum H, Schlaich M, Whitboum R, Sobotka P, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicenter safety and proof of principle cohort study. Lancet. 2009;373:1275-81. doi: 10.1016/S0140-6736(09)60566-3.
4. Esler MD, Krum H, Sobotka PA, Schlaich MP, et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (the Symplicity HTN-2 trial): a randomized controlled trial. Lancet. 2010;376:1903-9. doi: 10.1061/S0140-6736(10)62039-9.
5. Papademetriou V, Rashidi AA, Tsioufis C, Doumis M. Renal nerve ablation for resistant hypertension: how did we get here, present status and future directions. Circulation. 2014;129:1440-51. doi: 10.1161/CIRCULATIONAHA.113.005405.
6. Bhatt DL, Kandzari DE, O'Neill WW, D'Agostino R, Flack JM, Katzen BT, et al. SYMPLICITY HTN-3 Investigators. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370:1393-401. doi: 10.1056/NEJMoa1402670.
7. Patel HC, Hayward C, Di Mario C. Symplicity HTN 3: the death knell for renal denervation in hypertension? Glob Cardiol Sci Prac. 2014;15:95-8. doi: 10.5339/gcsp.2014.15.
8. Ukena C, Mahfoud F, Ewen S, Cremers B, et al. Renal denervation in the treatment of hypertension. Curr Hypertens Rep. 2013;15:363-9. doi: 10.1007/s11906-013-0363-2.
9. Calhoun DA, Jones D, Textor S, Goff DC, et al. Resistant hypertension: diagnosis, evaluation, and treatment. Circulation. 2008;117:e510-26. doi: 10.1161/CIRCULATIONAHA.108.189141.
10. Gaddam KK, Nishizaka MK, Pratt-Ubunama MN, Pimenta E, et al. Characterization of resistant hypertension: association between resistant hypertension, aldosterone and persistent intravascular volume expansion. Arch Intern Med. 2008;168(11):1159-64.
11. Clark D, Ahmed MI, Calhoun DA. Resistant hypertension and aldosterone: an update. Can J Cardiol. 2012;28:318-25. doi: 10.1016/j.cjca.2012.03.010.
12. Chobanian AV, Bakris GL, Black HR, Cushman WC, 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.
13. Vongpatanasin W. Resistant hypertension- a review of diagnosis and management. JAMA. 2014;311(21):2216-24. doi: 10.1001/jama.2014.5180.
14. Daughtery SL, Powers JD, Magid DJ, Masoudi FA, et al. The association between medical adherence and treatment intensification with blood pressure control in resistant hypertension. Hypertension. 2012;60:303-9. doi: 10.1161/HYPERTENSIONAHA.112.192096.
15. Jung O, Gechter JL, Wunder C, Paulke A, et al. Resistant hypertension? Assessment of adherence by toxicological urine analysis. J Hypertens. 2013;31:766-74. doi: 10.1097/HJH.0b013e32835e2286.
16. Strauch B, Petrak O, Zelinka T, Rosa J, et al. Precise assessment of noncompliance with the antihypertensive therapy in patients with resistant hypertension using toxicological serum analysis. J Hypertens. 2013;31:2455-61. doi: 10.1097/HJH.0b013e3283652c6116.
17. De la Sierra A, Segura J, Banegas JR, Gorostidi M, et al. Clinical features of 8295 patients with resistant hypertension classified on the basis of ambulatory blood pressure monitoring. Hypertension. 2011;57:898-902. doi: 10.1161/HYPERTENSIONAHA.110.168948.
18. Salles FG, Cardoso CRL, Muxfeldt ES. Prognostic influence of office and ambulatory blood pressure in resistant hypertension. Arch Intern Med. 2008;168:2340-6.
19. Perdomenico SD, Lapenna D, Buicci A, Tommaso R, et al. Cardiovascular outcome in treated hypertensive patients with responder, masked, false resistant and true resistant hypertension. Am J Hypertens. 2005;18:1422-8. doi: 10.1016/j.amjhyper.2005.05.014.
20. Egan BM, Li J. Role of aldosterone blockade in resistant hypertension. Semin Nephrol. 2014;34:273-84. doi: 10.1016/j.semnephrol.2014.04.004.
21. Bakhtar O, Ference BA, Hedquist LA, Levy PA, et al. Relationship of resistant hypertension and treatment outcomes with total arterial compliance in a predominantly African American hypertensive cohort. J Clin Hypertens. 2012;14:618-22. doi: 10.1111/j.1751-7176.2012.00653.x.
22. Shimbo D, Levitan EB, Booth JN, Calhoun DA, et al. The contributions of unhealthy lifestyle factors to apparent resistant hypertension: findings from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. J Hypertens. 2013;31:370-6. doi: 10.1097/HJH.0b013e32835b6be7.
23. Masuo K, Mikami H, Ogihara T, Tuck ML. Weight gain-induced blood pressure elevation. Hypertension. 2000;35:1135-40. doi: 10.1161/01.HYP.35.5.1135.
24. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults 1999-2008. JAMA. 2010;303(3):235-41.
25. Landsberg L, Aronne LJ, Beilin LJ, Burke V, et al. Obesity-related hypertension: pathogenesis, cardiovascular risk and treatment. J Clin Hypertens. 2013;15:14-33. doi: 10.111/jch.12049.
26. Flynn C. Increased aldosterone: mechanism of hypertension in obesity. Semin Nephrol. 2014;2014(34):340-8. doi: 10.1016/j.semnephrol.2014.04.009.
27. Goodfriend TL. Obesity, sleep apnea, aldosterone and hypertension. Curr Hypertens Rep. 2008;10:222-6.
28. Lozano L, Tovar JL, Sampol G, Romero O, et al. Continuous positive airway pressure treatment in sleep apnea patients with resistant hypertension; a randomized control trial. J Hypertens. 2010;28:2161-8. doi: 10.1097/HJH.0b013e32833b9c63.
29. Pedrosa RP, Drager LF, Gonzaga CC, Sousa MG, et al. Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension. Hypertension. 2011;58:811-7. doi: 10.1161/HYPERTENSIONAHA.111.179788.
30. Dudenbostal T, Calhoun DA. Resistant hypertension, obstructive sleep apnea and aldosterone. J Human Hypertens. 2012;26:281-7. doi: 10.1038/jhh.2011.47.
31. Martinez-Garcia MA, Capote F, Campos-Rodriguez F, Oberes P, 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(22):2407-15. doi: 10.1001/jama.2013.281250.
32. Androgue HJ, Madias NE. The impact of sodium and potassium on hypertension risk. Semin Nephrol. 2014;34:257-72. doi: 10.1016/j.semnephrol.2014.04.003.
33. Hirsch JS, Drexler Y, Bomback AS. Aldosterone blockade in chronic kidney disease. SeminNephrol. 2014;34:307-22. doi: 10.1016/j.semnephrol.2014.04.006.
34. Pimenta E, Calhoun DA. Resistant hypertension and aldosteronism. Curr Hypertens Rep. 2007;9:353-9.
35. Taler SJ, Textor SC, Augustine JE. Resistant hypertension: comparing hemodynamic management to specialist care. Hypertension. 2002;39:982-8. doi: 10.1161/.01.HYP.0000016176.16042.2F.
36. Gaddam I, Corros C, Pimenta E, Ahmed M, et al. Rapid reversal of left ventricular hypertrophy and intracardiac volume overload in patients with resistant hypertension and hyperaldosteronism; a prospective clinical study. Hypertension. 2010;55:1137-42. doi: 10.1161/HYPERTENSIONAHA.109.141531.
37. Tamargo J, Solini A, Ruilope LM. Comparison of agents that affect aldosterone action. Sem Nephrol. 2014;34:285-306. doi: 10.1016/j.semnephrol.2014.04.005.
38. De Haro Moraes C, Figueiredo VN, de Faria APC, Barbaro NT. High circulating leptin levels are associated with increased blood pressure in uncontrolled resistant hypertension. J Hum Hypertens. 2013;27:225-30. doi: 10.1038/jhh.2012.29.
39. De Faria APC, Demarq C, Figueiredo VN, Morales CH, et al. Hypoadiponectinemia and aldosterone excess are associated with lack of blood pressure control in subjects with resistant hypertension. Hypertens Res. 2013;36:1067-72. doi: 10.1038/hr.2013.92.
40. Shibata H, Itoh H. Mineralocorticoid receptor-associated hypertension and its organ damage: clinical relevance for resistant hypertension. Am J Hypertens. 2012;25:514-23. doi: 10.1038/ajh.2011.245.
41. Sechi LA, Colussi G, Di Fabio A, Catena C. Cardiovascular and renal damage in primary aldosteronism: outcomes after treatment. Am J Hypertens. 2010;23:1253-60. doi: 10.1038/ajh.2010.169.
42. Fujita T. Mechanism of salt-sensitive hypertension: focus on adrenal and sympathetic nervous systems. J Am Soc Nephrol. 2014;25:1148-55. doi: 10.1681/ASN.2013.12125.
43. Fox CS, Larson MG, Hwang SJ, et al. Cross-sectional relations of serum aldosterone and urine sodium excretion to urinary albumin excretion in a community-based sample. Kidney Int. 2006;69:2064-9. doi: 10.1038/sj.ki.5000378.
44. Cianciaruso B, Bellizi V, Minutolo R, et al. Salt intake and renal outcome in patients with progressive renal disease. Miner Electrolyte Metab. 1998;24:296-301. doi: 10.1159/000057385.
45. Pimenta E, Gaddam KK, Pratt-Ubunama MN, et al. Relation of dietary salt and aldosterone to urinary protein excretion in subjects with resistant hypertension. Hypertension. 2008;51:339-44. doi: 10.1161/HYPERTENSIONAHA.107.100701.
46. Jansen PM, Jan Danser AH, Imholz BP, van den Meiracker AH. Aldosterone-receptor antagonism in hypertension. J Hypertens. 2009;27:680-91. doi: 10.1097/HJH.Ob013e32832810ed.
47. Kasama S, Toyama T, Kumakura H, Takayama Y, et al. Effect of spironolactone on cardiac sympathic nerve activity and left ventricular remodeling in patients with dilated cardiomyopathy. J Am Coll Cardiol. 2003;41:574-81. doi: 10.1016/S0735-1097(02)02855-3.
48. Chai W, Garredls IM, de Vries R, Batenburg WW, et al. Nongenomic effects of aldosterone in the human heart: interaction with angiotensin II. Hypertension. 2005;46:701-6. doi: 10.1161/01.HYP.0000182661.98259.4f.
49. Lane DA, Beevers DG. Amiloride 10 mg is less effective than spironolactone 25 mg in patients with hypertension resistant to a multidrug regime including an angiotensin-blocking agent. J Hypertens. 2007;25:2515-6. doi: 10.1097/HJH.O6013e3281fc975a.
50. Mahmud A, Feely J. Aldosterone to renin ratio, arterial stiffness, and the response to aldosterone antagonism in essential hypertension. Am J Hypertens. 2005;18:50-5. doi: 10.1016/j.amjhyper.2004.08.026.
51. Sjostrom L, Lindroos AK, Peltonen M, Torgerson J, et al. Lifestyle, diabetes and cardiovascular risk factors 10 yr after bariatric surgery. N Engl J Med. 2004;351:2683-93.
52. Brethauer SA, Aminian A, Romero-Talamas H, Batayyah E, et al. Can diabetes be surgically cured: long term metabolic effects of bariatric surgery in obese patients with type 2 diabetes mellitus. Ann Surg. 2013;258(4):628-37. doi: 10.1097/SLA.0b013e3182a50346.
53. Pontiroli AE, Alberto M, Paganelli M, Saibene A, et al. Metabolic syndrome, hypertension, and diabetes mellitus after gastric banding; the role of aging and duration of obesity. Surg Obes Relat Dis. 2013;9:894-900. doi: 10.1016/j.soard.2013.04.001.
54. Ehrhart-Bornstein M, Lamounier-Zepter V, Schraven A, Langenbach J, et al. Human adipocytes secrete mineralocorticoid-releasing factors. Proc Natl Acad Sci USA. 2003;100(24):14211-6.
55. Gaddam K, Pimenta E, Thomas SJ, Cofield SS, et al. Spironolactone reduces severity of obstructive sleep apnea in patients with resistant hypertension: a preliminary report. J Hum Hypertens. 2010;24(8):532-7. doi: 10.1038/jhh.2009.9c.
56. De Nicola L, Gabbai FB, Agarwal R, Chiodini P, et al. Prevalence and prognostic role of resistant hypertension in chronic kidney disease patients. J Am Coll Cardiol. 2012;2013(61):2461-7. doi: 10.1016/jack.12.061.
57. Kidney Disease: improving global outcomes (KDIGO) CKD work group. KDIGO, 2012. Clinical practice guidelines s for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1-150. doi: 10.1038/K.sup.2012.64-72.
58. Uhlig K, Patel I, Ip S, Kitsios GD, et al. Self-measured blood pressure monitoring in the management of hypertension: a systematic review and meta-analysis. Ann Intern Med. 2013;159:185-94.
59. Pimenta E, Gaddam KK, Oparil S, Aban I, et al. Effects of dietary sodium reduction on blood pressure in subjects with resistant hypertension. Hypertension. 2009;54:475-81. doi: 10.1161/HYPERTENSIONAHA.109.131235.
60. James PA, Oparil S, Carter BL, Cushman WC, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the 8th Joint National Committee (JNC 8). JAMA. 2014;311(5):507-20. doi: 10.1001/jama.2013.284427.
61. Mancia G, De Baker G, Dominiczak A, Cifkova R, et al. Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension and of the European Society of Cardiology. J Hypertens. 2007;25:1105-87. doi: 10.1092/HJH.06013e3281fc975a.
62. Kumar N, Calhoun DA, Dudenbostel T. Management of patients with resistant hypertension: current treatment options. Integr Blood Press Control. 2013;6:139-51.
63. Ernst ME, Moser M. Use of diuretics in patients with hypertension. N Engl J Med. 2009;361:2153-64.
64. Brown A, Captain B. 50 years of thiazides: should thiazide diuretics be considered third-line hypertensive treatment. Am J Hypertens. 2011;18:e244-54.
65. Gorostidi M, de la Sierr A. Combination therapy in hypertension. Adv Ther. 2013;30(4):320-36. doi: 10.1007/s12325-013-0020.9.
66. Flack JM, Sica DA, Bakris G, Brown AL, et al. Management of high blood pressure in Blacks: an update of the International Society on Hypertension in Blacks consensus statement. Hypertension. 2010;56:1-21. doi: 10.1161/HYPERTENSIONAHA.110.152892.
67. Hypertensive Detection and Follow-up Program Cooperative Group. The effects of treatment on mild hypertension: results of the Hypertension Detection and Follow-up Program. N Engl J Med. 1982;307:976-80.
68. Multiple Risk Factor Intervention Trial Research Group. Mortality after 10.5 years for hypertensive participants in the Multiple Risk Factor Intervention Trial. Circulation. 1990;82:1616-28. doi: 10.1161/01.CIR.82.5.1616.
69. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. JAMA. 1991;265:3255-64.
70. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. 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.
71. Wing LM, Reid CM, Ryan P, et al. A comparison of outcomes with angiotensin-converting enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med. 2003;348:583-92.
72. Jamerson K, Weber MA, Bakris GI, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359:2417-28.
73. Ernst ME, Carter BL, Goerdt CJ, Steffenmeier JJG, et al. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone in ambulatory and office blood pressure. Hypertension. 2006;47:352-8. doi: 10.1161/01.HYP.0000203309.07140.d3.
74. Ernst ME, Lund BC. Renewed interest in chlorthalidone: evidence from the Veterans Health Administration. J Clin Hypertens. 2010;12:927-34. doi: 10.1111/j.1751-7176.2010.00373.x.
75. Saha C, Eckert GJ, Ambrosius WT, Chun TY, et al. Improvement in blood pressure with inhibition of the epithelial sodium channel in blacks with hypertension. Hypertension. 2005;46:481-7. doi: 10.1161/01.HYP.0000179582.42830.1d.
76. Ouzan J, Perault C, Lincoff AM, Carre E, et al. The role of spironolactone in the treatment of patients with refractory hypertension. Am J Hypertens. 2002;15:333-9.
77. Nishizaka MK, Zaman MA, Calhoun DA. Efficacy of low dose spironolactone in subjects with resistant hypertension. Am J Hypertens. 2003;16:925-30. doi: 10.1016/s0895-7061(03)01032-x.
78. Sharabi Y, Adler E, Shamis A, Nussinovitch N, et al. Efficacy of add-on aldosterone receptor blocker in uncontrolled hypertension. Am J Hypertens. 2006;19:750-5. doi: 10.1016/j.amjhypertens.2005.11.016.
79. Chapman N, Dobson J, WilsonS Dahlof B, et al. Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension. 2007;49:839-45. doi: 10.1161/01.HYP.0000259805.18468.8c.
80. Lane DA, Shah S, Beevers DG. Low dose spironolactone in the management of resistant hypertension: a surveillance study. J Hypertens. 2007;25:891-4. doi: 10.1097/HJH.0b013e.3280114954d.
81. De Souza F, Muxfeldt E, Fiszman R, Salles G. Efficacy of spironolactone therapy in patients with true resistant hypertension. Hypertension. 2010;55:147-52. doi: 10.1161/HYPERTENSIONAHA.109.140988.
82. Alvarez-Alvarez B, Abad-Cardiel M, Fernandez-Cruz A, Martell-Claros N. Management of resistant arterial hypertension: role of spironolactone versus double blockage of the renin-angiotensin-aldosterone system. J Hypertens. 2010;28:2329-35. doi: 10.1097/HJH.0b013e32833d4c99.
83. Vaclavik J, Sedlak R, Plachy M, Navratil K, et al. Addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT): a randomized double-blind, placebo-controlled trial. Hypertension. 2011;57:1069-75. doi: 10.1161/HYPERTENSIONAHA.111.169961.
84. Oxlund CS, Henriksen JE, Tarnow L, Schousboe K, et al. 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. doi: 10.1097/hjh.0b013e3283638b1a.
85. Karns AD, Bral JM, Hartman D, Peppard T, et al. Study of aldosterone synthetase inhibition as an add-on therapy in resistant hypertension. J Clin Hypertens. 2013;15:186-92. doi: 10.1111/jch.12051.
86. Abolghasmi R, Taziki O. Efficacy of low dose spironolactone in chronic kidney disease with resistant hypertension. Saudi J Kidney Dis Transplant. 2011;22(1):75-8.
87. Dietz JD, Du S, Bolten CW, Payne MA, et al. A number of marketed dihydropyridine calcium channel blockers have mineralocorticoid receptor antagonist activity. Hypertension. 2008;51:742-8. doi: 10.1161/HYPERTENSIONAHA.107.103580.
88. Kosaka H, Hirayama K, Yoda N, Sasaki K, et al. The L-, N- and T-type triple calcium channel blocker benidipine acts as an antagonist of mineralocorticoid receptor, a member of nuclear receptor family. Eur J Pharmacol. 2010;635:49-55. doi: 10.10016/j.ejphar.2010.03.018.
89. Colussi G, Catena C, Sechi LA. Spironolactone, eplerenone, and the new aldosterone blockers in endocrine and primary hypertension. J Hypertens. 2012;31:3-15. doi: 10.1097/HJH.0b013e3283599bba.
90. Paulis L, Steckelings UM, Unger T. Key advances in antihypertensive treatment. Nat Rev Cardiol. 2012;9:276-85. doi: 10.1038/nrcardio.2012.33.
91. Lazich I, Bakris GL. Prediction and management of hyperkalemia across the spectrum of chronic kidney disease. Semin Nephrol. 2014;34:333-9. doi: 10.1016/jsemnephrol.2014.04.008.
92. Yoshitoma Y, Kawanishi KI, Yamaguchi A, Sakurai SI, et al. Effectiveness of the direct renin inhibitor aliskerin in patients with resistant hypertension. Int Heart J. 2013;54:88-92.
93. Harel Z, Gilbert C, Wald R, Bell C, et al. The effect of combination treatment with aliskerin and blockers of the renin-angiotensin-aldosterone system on hyperkalemia and acute kidney injury: systematic review and meta-analysis. BMJ. 2012;344:e42. doi: 10.1136/bmj.e42.
94. Robles NR, Cerezo I, Hernandez-Gallego R. Renin-angiotensin system blocking drugs. J Cardiovasc Pharmacol Ther. 2014;19(1):14-33. doi: 10.1177/1074248413501018.
95. Amar L, Azizi M, Menard J, Peyrard S, et al. Aldosterone synthetase inhibition with LCI699. Hypertension. 2010;56:831-8. doi: 10.1161/HYPERTENSIONAHA.110.157271.
96. Calhoun DA, white WB, Krum H, Guo W, et al. Effects of a novel aldosterone synthetase inhibitor for treatment of primary hypertension: results of a randomized double-blind placebo and active-controlled phase 2 trial. Circulation. 2011;124:1945-55. doi: 10.1161/CIRCULATIONAHA.111.029892.
97. 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(4):285-9. doi: 10.1177/1470320313513408.