Role of Aldosterone Blockade in Resistant Hypertension
Abstract
Apparent treatment-resistant hypertension (aTRH), defined as uncontrolled blood pressure using 3 or more antihypertensive medications or controlled using 4 or more antihypertensive medications, affects approximately 30% of uncontrolled and 12% of controlled blood pressure (BP) patients. aTRH is used when pseudoresistance cannot be excluded (eg, BP measurement artifacts, mainly office resistance, suboptimal adherence, suboptimal treatment regimens, and true TRH). True TRH comprises approximately 30% to 50% of TRH. Patients with TRH have a high prevalence of obesity, insulin resistance, sleep apnea, and volume expansion. Aldosterone, a mineralocorticoid, is an important contributor to TRH, with primary aldosteronism present in approximately 20% of patients. Spironolactone, a mineralocorticoid-receptor antagonist, as a fourth-line agent, decreases BP 20 to 25/10 to 12 mm Hg in TRH patients with and without primary aldosteronism. The BP response to spironolactone is roughly double that of other classes of antihypertensive medications in TRH. Although approximately 70% of patients with uncontrolled TRH have estimated glomerular filtration rate of 50 or greater and a serum potassium level of 4.5 or less, which are associated with a low risk for hyperkalemia, only a small percentage receive a mineralocorticoid-receptor antagonist. This review examines the clinical epidemiology and pharmacotherapy of controlled and uncontrolled hypertension with an emphasis on aTRH, the role of aldosterone in blood pressure regulation, and the potential benefits of mineralocorticoid-receptor antagonist in uncontrolled TRH.
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Approximately 70% of adults with resistant hypertension are candidates for mineralocorticoid receptor antagonists based on eGFR and serum K+, yet only a small fraction receive these effective agents.
“Approximately 70% of adults with RH are candidates for mineralocorticoid receptor antagonists based on eGFR and serum K+, yet only a small fraction receive these effective agents.379”
From Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association (2018) · cites this paper as [379]
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- Authors
- Egan, B. M., & Li, J.
- Affiliations
- Prisma Health (US)
- College of Charleston (US)
- Venue
- Seminars in Nephrology
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 34
- Issue
- 3
- Pages
- 273-284
- ISSN
- 0270-9295 (ISSN-L)
- OpenAlex
- W2088538958
- Cited by
- 33
- References
- 62
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 3 · 2021: 2 · 2020: 8 · 2018: 2 · 2017: 4 · 2016: 2 · 2015: 5
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Nephrology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R34HL105880, HL105880)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- resistant hypertension, aldosterone, mineralocorticoid receptor antagonists, spironolactone, primary aldosteronism, blood pressure regulation, hyperkalemia, antihypertensive therapy, pseudoresistance
- MeSH terms
- Mineralocorticoid Receptor Antagonists, Blood Pressure Determination, Clinical Trials as Topic, Drug Resistance, Glomerular Filtration Rate, Humans, Hypertension, Insulin Resistance, Kidney, Sodium, Spironolactone, Medication Adherence
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