Trial reportJournal of hypertension2013
Aldosterone synthase inhibition for the treatment of hypertension and the derived mechanistic requirements for a new therapeutic strategy.
Trial report in Journal of hypertension, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 3 syntheses or guidelines pooled it, 53 citations in OpenAlex.
- Aldosterone Synthase Inhibitors for Resistant Hypertension: Pharmacological Insights - A Systematic Review.Drugs · 2025Pooled it
- Efficacy and Safety of Lorundrostat in Uncontrolled Hypertension: A Systematic Review and Meta-Analysis.Journal of clinical hypertension (Greenwich, Conn.) · 2025Pooled it
- Efficacy and Safety of Aldosterone Synthase Inhibitors in Hypertension: A Systematic Review and Meta-Analysis.Endocrinology, diabetes & metabolism · 2025Pooled it
- Aldosterone Synthase Inhibitors: Emerging Therapeutic Strategies in Resistant Hypertension.Life (Basel, Switzerland) · 2026Review
- Emerging Medical Therapies for Primary Aldosteronism.Hypertension (Dallas, Tex. : 1979) · 2026Review
- Unmasking Hormonal Mechanisms of Hypertension in Obesity.JACC. Basic to translational science · 2026Article
- Review
- Unmasking Hormonal Mechanisms of Hypertension in Obesity.medRxiv : the preprint server for health sciences · 2025Article
- Review
- The Emerging Role of Aldosterone Synthase Inhibitors in Overcoming Renin-Angiotensin-Aldosterone System Therapy Limitations: A Narrative Review.Cardiac failure review · 2025Review
- Aldosterone Synthase Inhibitors for Cardiorenal Protection: Ready for Prime Time?Kidney & blood pressure research · 2024Review
- Selectivity of osilodrostat as an inhibitor of human steroidogenic cytochromes P450.The Journal of steroid biochemistry and molecular biology · 2023Article
- Review
- Human cytochrome P450 11B2 produces aldosterone by a processive mechanism due to the lactol form of the intermediate 18-hydroxycorticosterone.The Journal of biological chemistry · 2019Article
- Development of Highly Selective Pyrimidine-Based Aldosterone Synthase (CYP11B2) Inhibitors.ACS medicinal chemistry letters · 2019Article
- Progress in the Management of Primary Aldosteronism.American journal of hypertension · 2018Review
- Interventional procedures and future drug therapy for hypertension.European heart journal · 2017Review
- Preclinical and Early Clinical Profile of a Highly Selective and Potent Oral Inhibitor of Aldosterone Synthase (CYP11B2).Hypertension (Dallas, Tex. : 1979) · 2017Article
- New developments in the pharmacological treatment of hypertension: dead-end or a glimmer at the horizon?Current hypertension reports · 2015Review
- Cortisol dysregulation in obesity-related metabolic disorders.Current opinion in endocrinology, diabetes, and obesity · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
contextWe describe the clinical investigation of the first generation aldosterone synthase inhibitor, LCI699, in patients with essential, uncontrolled, resistant, or secondary hypertension. LCI699 competitively reduced blood pressure at lower doses yet counterintuitive effects were observed at higher doses. OBJECTIVE AND
methodAn extensive endocrine biomarker analysis was performed to better understand the pharmacological mechanism of the drug.
resultsThe interference of LCI699 in the renin-angiotensin-aldosterone system occurred with limited target selectivity, as a dose-dependent compensatory stimulation of the hypothalamic-pituitary-adrenal feedback axis was discovered. Thus, LCI699 affected two endocrine feedback loops that converged at a single point, inhibiting the 11β-hydroxylase reaction in the adrenal gland, leading to supraphysiological levels of 11-deoxycortiscosterone. The accumulation of this potent mineralocorticoid may explain the blunted blood pressure response to LCI699.
conclusionFuture aldosterone synthase inhibitors may improve their target selectivity by sparing the 11β-hydroxylase reaction and preferentially inhibiting one of the two other enzymatic reactions mediated by aldosterone synthase.
Indexed as
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.