Efficacy of Spironolactone Therapy in Patients With True Resistant Hypertension
Abstract
The role of spironolactone in resistant hypertension management is unclear. The aim of this prospective trial was to evaluate the antihypertensive effect of spironolactone in patients with true resistant hypertension diagnosed by ambulatory blood pressure monitoring. A total of 175 patients had clinical and complementary exams obtained at baseline and received spironolactone in doses of 25 to 100 mg/d. A second ambulatory blood pressure monitoring was performed after a median interval of 7 months. Paired Student t test was used to assess differences in blood pressure before and during spironolactone administration, and multivariate analysis adjusted for age, sex, and number of antihypertensive drugs to assess the predictors of blood pressure fall. There were mean reductions of 16 and 9 mm Hg, respectively, in 24-hour systolic and diastolic blood pressures (95% CIs: 13 to 18 and 7 to 10 mm Hg; P <0.001). Office systolic blood pressure and diastolic blood pressure also decreased (14 and 7 mm Hg). Controlled ambulatory blood pressure was reached in 48% of patients. Factors associated with better response were higher waist circumference, lower aortic pulse wave velocity, and lower serum potassium. No association with plasma aldosterone or aldosterone:renin ratio was found. Adverse effects were observed in 13 patients (7.4%). A third ambulatory blood pressure monitoring performed in 78 patients after a median of 15 months confirmed the persistence of the spironolactone effect. In conclusion, spironolactone administration to true resistant hypertensive patients is safe and effective in decreasing blood pressure, especially in those with abdominal obesity and lower arterial stiffness. Its addition to an antihypertensive regimen as the fourth or fifth drug is recommended.
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In patients with obesity and treatment-resistant hypertension treated with spironolactone, reductions in blood pressure did not correlate with plasma aldosterone concentration.
“Moreover, in patients with obesity and treatment-resistant hypertension who were treated with spironolactone, the resulting reductions in BP did not correlate with plasma aldosterone concentration73,74.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [74]
Administration of MR antagonists provides significant antihypertensive benefit in treatment resistant obese patients, although there was no correlation between plasma aldosterone levels and BP responses to MR blockade.
“Administration of MR antagonists provides significant antihypertensive benefit in treatment resistant obese patients, although there was no correlation between plasma aldosterone levels and BP responses to MR blockade52,53.”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [52]
In patients who are not overtly volume overloaded but who have evidence of low renin status or salt sensitivity of BP, mineralocorticoid receptor antagonists (spironolactone or eplerenone) are more successful than α- or β-blockers.
“In patients who are not overtly volume overloaded but who have evidence of low renin status or salt sensitivity of BP, mineralocorticoid receptor antagonists (spironolactone or eplerenone) are more successful than α- or β-blockers.373,377”
From Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association (2018) · cites this paper as [377]
Recent reports document the efficacy of mineralocorticoid receptor blockade to improve BP in patients with resistant hypertension.
“Recent reports document the efficacy of mineralocorticoid receptor blockade (Figure 3, step 3, and Table 4) to improve BP in patients with RH.373–377”
From Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association (2018) · cites this paper as [377]
Mineralocorticoid receptor blockade has beneficial effects on blood pressure in obese subjects even in those displaying resistant hypertension.
“These observations are also consistent with the beneficial effects of mineralocorticoid receptor blockade on blood pressure in obese subjects even in those displaying resistant hypertension (55).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [55]
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Self-citation
- Authors
- de Souza, F., Muxfeldt, E., Fiszman, R., & Salles, G.
- Affiliations
- From the Hypertension Program, University Hospital Clementino Fraga Filho, Medical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
- Universidade Federal do Rio de Janeiro (BR)
- Venue
- Hypertension
- Published
- 2010-01
- Volume
- 55
- Issue
- 1
- Pages
- 147-152
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2135100154
- Cited by
- 234
- References
- 32
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 10 · 2019: 8 · 2018: 11 · 2017: 13 · 2016: 18 · 2015: 19 · 2014: 26 · 2013: 31 · 2012: 26
- FWCI
- 15.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- spironolactone, resistant hypertension, antihypertensive therapy, ambulatory blood pressure monitoring, blood pressure reduction, predictors of treatment response, waist circumference, abdominal obesity, arterial stiffness, pulse wave velocity, serum potassium, aldosterone, adverse effects
- MeSH terms
- Blood Pressure, Breast Diseases, Diuretics, Follow-Up Studies, Gynecomastia, Humans, Hypertension, Prospective Studies, Spironolactone, Multivariate Analysis, Linear Models, Treatment Outcome, Blood Pressure Monitoring, Ambulatory
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