Skip to main content
Top
Published in: Current Hypertension Reports 5/2016

Open Access 01-05-2016 | Hypertension and the Kidney (RM Carey, Section Editor)

New Evidence Supporting the Use of Mineralocorticoid Receptor Blockers in Drug-Resistant Hypertension

Authors: Hafid Narayan, David J. Webb

Published in: Current Hypertension Reports | Issue 5/2016

Login to get access

Abstract

Treatment resistant hypertension (TRH), defined as a blood pressure above goal despite treatment with optimally tolerated doses of 3 antihypertensive agents of different classes, ideally including a diuretic, remains a significant problem and its management an area of uncertainty for physicians. One hypothesis is that resistant hypertension is due to abnormal sodium retention, mediated by aldosterone breakthrough occurring despite blockade of the renin-angiotensin-aldosterone system with angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). Thus, there has been renewed interest in the use of mineralocorticoid receptor blockers (MRB) to treat this condition. This article critically evaluates new evidence supporting the use of MRB in TRH published in the last 3 years. We conclude that there is now sufficient evidence to recommend MRB, in particular spironolactone, as the first choice medication to treat this condition, and for its inclusion in future guidelines.
Literature
1.
go back to reference Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2224–60.CrossRefPubMedPubMedCentral Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2224–60.CrossRefPubMedPubMedCentral
2.
go back to reference National Institute for Health and Care Excellence. Hypertension—clinical management of primary hypertension in adults. 2011. National Institute for Health and Care Excellence. Hypertension—clinical management of primary hypertension in adults. 2011.
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;57:898–902.CrossRefPubMed 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.CrossRefPubMed
4.
5.
go back to reference Vasan RS, Evans JC, Larson MG, Wilson PWF, Meigs JB, Rifai N, et al. Serum aldosterone and the incidence of hypertension in nonhypertensive persons. N Engl J Med. 2004;351:33–41.CrossRefPubMed Vasan RS, Evans JC, Larson MG, Wilson PWF, Meigs JB, Rifai N, et al. Serum aldosterone and the incidence of hypertension in nonhypertensive persons. N Engl J Med. 2004;351:33–41.CrossRefPubMed
6.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
7.
go back to reference Calhoun DA, Nishizaka MK, Zaman MA, Thakkar RB, Weissmann P. Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension. 2002;40:892–6.CrossRefPubMed Calhoun DA, Nishizaka MK, Zaman MA, Thakkar RB, Weissmann P. Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension. 2002;40:892–6.CrossRefPubMed
8.
go back to reference Bomback AS, Klemmer PJ. The incidence and implications of aldosterone breakthrough. Nat Clin Pract Nephrol. 2007;3:486–92.CrossRefPubMed Bomback AS, Klemmer PJ. The incidence and implications of aldosterone breakthrough. Nat Clin Pract Nephrol. 2007;3:486–92.CrossRefPubMed
9.
go back to reference Sica DA. Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium homeostasis. Heart Fail Rev. 2005;10:23–9.CrossRefPubMed Sica DA. Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium homeostasis. Heart Fail Rev. 2005;10:23–9.CrossRefPubMed
10.
go back to reference Roush GC, Ernst ME, Kostis JB, Yeasmin S, Sica DA. Dose doubling, relative potency, and dose equivalence of potassium-sparing diuretics affecting blood pressure and serum potassium. J Hypertens. 2016;34:11–9.CrossRefPubMed Roush GC, Ernst ME, Kostis JB, Yeasmin S, Sica DA. Dose doubling, relative potency, and dose equivalence of potassium-sparing diuretics affecting blood pressure and serum potassium. J Hypertens. 2016;34:11–9.CrossRefPubMed
11.
go back to reference Chapman N, Dobson J, Wilson S, Dahlöf B, Sever PS, Wedel H, et al. Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension. 2007;49:839–45.CrossRefPubMed Chapman N, Dobson J, Wilson S, Dahlöf B, Sever PS, Wedel H, et al. Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension. 2007;49:839–45.CrossRefPubMed
12.
go back to reference Lane DA, Shah S, Beevers DG. Low-dose spironolactone in the management of resistant hypertension: a surveillance study. J Hypertens. 2007;25:891–4.CrossRefPubMed Lane DA, Shah S, Beevers DG. Low-dose spironolactone in the management of resistant hypertension: a surveillance study. J Hypertens. 2007;25:891–4.CrossRefPubMed
13.
go back to reference Nishizaka M, Zaman MA, Calhoun DA. Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am J Hypertens. 2003;16:925–30.CrossRefPubMed Nishizaka M, Zaman MA, Calhoun DA. Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am J Hypertens. 2003;16:925–30.CrossRefPubMed
14.
go back to reference Rodilla E, Costa JA, Pérez-Lahiguera F, Baldó E, González C, Pascual JM. Spironolactone and doxazosin treatment in patients with resistant hypertension. Rev Esp Cardiol. 2009;62:158–66.CrossRefPubMed Rodilla E, Costa JA, Pérez-Lahiguera F, Baldó E, González C, Pascual JM. Spironolactone and doxazosin treatment in patients with resistant hypertension. Rev Esp Cardiol. 2009;62:158–66.CrossRefPubMed
15.
go back to reference Engbaek M, Hjerrild M, Hallas J, Jacobsen I. The effect of low-dose spironolactone on resistant hypertension. J Am Soc Hypertens. 2010;4:290–4.CrossRefPubMed Engbaek M, Hjerrild M, Hallas J, Jacobsen I. The effect of low-dose spironolactone on resistant hypertension. J Am Soc Hypertens. 2010;4:290–4.CrossRefPubMed
16.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
17.
go back to reference Calhoun DA, White WB. Effectiveness of the selective aldosterone blocker, eplerenone, in patients with resistant hypertension. J Am Soc Hypertens. 2008;2:462–8.CrossRefPubMed Calhoun DA, White WB. Effectiveness of the selective aldosterone blocker, eplerenone, in patients with resistant hypertension. J Am Soc Hypertens. 2008;2:462–8.CrossRefPubMed
18.
go back to reference Djoumessi R, Katte J, Kaze F, Menanga A, Sobngwi E, Mbanya J. OP51 Resistant hypertension among a group of type 2 diabetic patients: the effect of spironolactone. Diabetes Res Clin Pract. 2014;103:S22–3.CrossRef Djoumessi R, Katte J, Kaze F, Menanga A, Sobngwi E, Mbanya J. OP51 Resistant hypertension among a group of type 2 diabetic patients: the effect of spironolactone. Diabetes Res Clin Pract. 2014;103:S22–3.CrossRef
19.•
go back to reference 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. J Hypertens. 2013;31:2094–102. Randomised trial comparing spironolactone to placebo in TRH, showing safety and superiority of spironolactone to placebo.CrossRefPubMed 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. J Hypertens. 2013;31:2094–102. Randomised trial comparing spironolactone to placebo in TRH, showing safety and superiority of spironolactone to placebo.CrossRefPubMed
20.
go back to reference Vaclavik J, Sedlak R, Jarkovsky J, Kocianova E, Taborsky M. The effect of spironolactone in patients with resistant arterial hypertension in relation to baseline blood pressure and secondary causes of hypertension. Biomed Pap. 2013;157:50–5.CrossRef Vaclavik J, Sedlak R, Jarkovsky J, Kocianova E, Taborsky M. The effect of spironolactone in patients with resistant arterial hypertension in relation to baseline blood pressure and secondary causes of hypertension. Biomed Pap. 2013;157:50–5.CrossRef
21.
go back to reference Ni X, Zhang J, Zhang P, Wu F, Xia M, Ying G, et al. Effects of spironolactone on dialysis patients with refractory hypertension: a randomized controlled study. J Clin Hypertens. 2014;16:658–63.CrossRef Ni X, Zhang J, Zhang P, Wu F, Xia M, Ying G, et al. Effects of spironolactone on dialysis patients with refractory hypertension: a randomized controlled study. J Clin Hypertens. 2014;16:658–63.CrossRef
22.
go back to reference Rosa J, Widimsky P, Tou ek P, Petrak O, Urila K, Waldauf P, et al. Randomized comparison of renal denervation versus intensified pharmacotherapy including spironolactone in true-resistant hypertension: six-month results from the Prague-15 study. Hypertension. 2015;65:407–13.CrossRefPubMed Rosa J, Widimsky P, Tou ek P, Petrak O, Urila K, Waldauf P, et al. Randomized comparison of renal denervation versus intensified pharmacotherapy including spironolactone in true-resistant hypertension: six-month results from the Prague-15 study. Hypertension. 2015;65:407–13.CrossRefPubMed
23.
go back to reference Verdalles U, de Vinuesa SG, Goicoechea M, Macias N, Santos A, de Jose AP, et al. Management of resistant hypertension: aldosterone antagonists or intensification of diuretic therapy? Nephrology (Carlton). 2015;20:567–71.CrossRef Verdalles U, de Vinuesa SG, Goicoechea M, Macias N, Santos A, de Jose AP, et al. Management of resistant hypertension: aldosterone antagonists or intensification of diuretic therapy? Nephrology (Carlton). 2015;20:567–71.CrossRef
24.••
go back to reference Williams B, MacDonald TM, Morant S, Webb DJ, Sever P, McInnes G, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015;6736:1–10. Randomised trial comparing spironolactone to active comparators in TRH, showing superiority of spironolactone to bisoprolol and doxazosin. Williams B, MacDonald TM, Morant S, Webb DJ, Sever P, McInnes G, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015;6736:1–10. Randomised trial comparing spironolactone to active comparators in TRH, showing superiority of spironolactone to bisoprolol and doxazosin.
25.
go back to reference Václavík J, Sedlák R, Jarkovský J, Kociánová E, Táborský M. Effect of spironolactone in resistant arterial hypertension. Medicine (Baltimore). 2014;93:1–9. Václavík J, Sedlák R, Jarkovský J, Kociánová E, Táborský M. Effect of spironolactone in resistant arterial hypertension. Medicine (Baltimore). 2014;93:1–9.
26.
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. N Engl J Med. 2014;370:1393–401.CrossRefPubMed 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.CrossRefPubMed
27.•
go back to reference 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. Showed high rates of poor medication adherence in patients with hypertension using mass spectrometry analysis of urine samples.CrossRefPubMedPubMedCentral 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. Showed high rates of poor medication adherence in patients with hypertension using mass spectrometry analysis of urine samples.CrossRefPubMedPubMedCentral
28.
go back to reference Dahal K, Kunwar S, Rijal J, Alqatahni F, Panta R, Ishak N, et al. The effects of aldosterone antagonists in patients with resistant hypertension: a meta-analysis of randomized and nonrandomized studies. Am J Hypertens. 2015;28:1–10.CrossRef Dahal K, Kunwar S, Rijal J, Alqatahni F, Panta R, Ishak N, et al. The effects of aldosterone antagonists in patients with resistant hypertension: a meta-analysis of randomized and nonrandomized studies. Am J Hypertens. 2015;28:1–10.CrossRef
29.
go back to reference Guo H, Xiao Q. Clinical efficacy of spironolactone for resistant hypertension : a meta analysis from randomized controlled clinical trials. Int J Clin Exp Med. 2015;8:7270–8.PubMedPubMedCentral Guo H, Xiao Q. Clinical efficacy of spironolactone for resistant hypertension : a meta analysis from randomized controlled clinical trials. Int J Clin Exp Med. 2015;8:7270–8.PubMedPubMedCentral
Metadata
Title
New Evidence Supporting the Use of Mineralocorticoid Receptor Blockers in Drug-Resistant Hypertension
Authors
Hafid Narayan
David J. Webb
Publication date
01-05-2016
Publisher
Springer US
Published in
Current Hypertension Reports / Issue 5/2016
Print ISSN: 1522-6417
Electronic ISSN: 1534-3111
DOI
https://doi.org/10.1007/s11906-016-0643-8

Other articles of this Issue 5/2016

Current Hypertension Reports 5/2016 Go to the issue

Hypertension and the Kidney (RM Carey, Section Editor)

Role of Phosphodiesterase 5 and Cyclic GMP in Hypertension

Resistant Hypertension (E Pimenta, Section Editor)

Resistant Hypertension and Chronic Kidney Disease: a Dangerous Liaison

Blood Pressure Monitoring and Management (J Cockcroft, Section Editor)

Hypertension in the Emergency Department

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.