Study of Aldosterone Synthase Inhibition as an Add‐On Therapy in Resistant Hypertension
Open accessAbstract
Aldosterone inhibition with mineralcorticoid receptor antagonists (MRAs) is an effective treatment for resistant hypertension. Aldosterone synthase inhibitors (ASIs) are currently being investigated as a new therapeutic strategy to reduce aldosterone secretion from the adrenal gland. In this study, the efficacy and safety of the first‐generation ASI LCI699 (0.25 mg twice daily, 1 mg 4 once daily, and 0.5 mg/1 mg twice daily) was compared with placebo and eplerenone (50 mg twice daily), in patients with resistant hypertension. Placebo‐adjusted decreases in systolic blood pressure (BP) with LCI699 ranged from 2.6 mm Hg to 4.3 mm Hg at week 8; changes in diastolic BP ranged from +0.3 mm Hg to −1.2 mm Hg. However, reductions were smaller than observed with eplerenone 50 mg twice daily (9.9 mm Hg and 2.9 mm Hg for systolic and diastolic BP, respectively) and not statistically significant vs placebo. LCI699 suppressed plasma aldosterone levels in a dose‐related manner with corresponding dose‐dependent increases in plasma renin activity and plasma 11‐deoxycorticosterone. LCI699 and eplerenone were well tolerated. These data demonstrate that aldosterone synthesis inhibition with LCI699 lowers BP modestly in patients with resistant hypertension. Aldosterone synthesis inhibition might offer an attractive adjunct to aldosterone receptor blockade, although the potential of a combination MRA/ASI has not yet been tested. J Clin Hypertens (Greenwich). 2012;00:00–00. ©2012 Wiley Periodicals, Inc.
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In patients with resistant hypertension and an average BMI of approximately 32 kg/m2, aldosterone synthase inhibition with LCI699 reduced plasma aldosterone concentration but caused minimal reductions in blood pressure, substantially less than those achieved with an MR antagonist.
“Another study in patients with resistant hypertension and an average BMI of −32 kg/m2 reported that aldosterone synthase inhibition using LC1699 reduced plasma aldosterone concentration but caused minimal reductions in BP that were substantially less than those achieved with an MR antagonist80.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [80]
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- Authors
- Karns, A. D., Bral, J. M., Hartman, D., Peppard, T., & Schumacher, C.
- Affiliations
- Novartis (Switzerland) (CH)
- Corresponding author
- Karns, Adam D.
- ORCID
- Peppard, Thomas
- Venue
- The Journal of Clinical Hypertension
- Publisher
- Wiley
- Published
- 2012-12-14
- Volume
- 15
- Issue
- 3
- Pages
- 186-192
- ISSN
- 1524-6175 (ISSN-L)
- 1751-7176
- PMC
- PMC8033888
- OpenAlex
- W1521917359
- Cited by
- 104
- References
- 31
- Citations by year
- 2026: 19 · 2025: 14 · 2024: 6 · 2023: 8 · 2022: 4 · 2021: 1 · 2019: 6 · 2018: 6 · 2017: 6 · 2016: 7 · 2015: 13 · 2014: 11 · 2013: 3
- FWCI
- 7.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Hypertension (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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
- aldosterone synthase inhibitors, resistant hypertension, eplerenone, mineralocorticoid receptor antagonists, blood pressure reduction, plasma aldosterone, plasma renin activity, deoxycorticosterone, drug safety and tolerability, adjunctive therapy
- MeSH terms
- Eplerenone, Adolescent, Adult, Aged, Mineralocorticoid Receptor Antagonists, Antihypertensive Agents, Blood Pressure, Double-Blind Method, Female, Humans, Hypertension, Iceland, Imidazoles, Male, Middle Aged, Prospective Studies, Pyridines, Spironolactone, United States, Treatment Outcome, Cytochrome P-450 CYP11B2, Young Adult
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