The Emerging Role of Aldosterone Synthase Inhibitors in Overcoming Renin–Angiotensin–Aldosterone System Therapy Limitations: A Narrative Review
Bibliographic record
Abstract
The renin-angiotensin-aldosterone system is integral to cardiorenal health, with aldosterone controlling fluid balance, blood pressure and cardiac remodelling. Despite the widespread use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and mineralocorticoid receptor antagonists, 'aldosterone escape' persists, contributing to treatment failure and adverse outcomes. Steroidal mineralocorticoid receptor antagonists also cause hyperkalaemia and anti-androgenic effects, limiting their use. Aldosterone synthase inhibitors (ASIs) selectively block cytochrome P450 11B2, reducing pathological aldosterone levels while preserving basal mineralocorticoid receptor activity, thus potentially lowering hyperkalaemia risk. This narrative review identified 41 relevant publications from a PubMed/MEDLINE search of "aldosterone synthase inhibitor" through 11 January 2025. Early clinical trials of ASIs (baxdrostat, lorundrostat, vicadrostat, dexfadrostat phosphate, JX09) report significant reductions in aldosterone, blood pressure and albuminuria, with promising safety. Challenges include ensuring high selectivity, mitigating hyperkalaemia and establishing long-term benefits. Ongoing Phase III trials will clarify their efficacy, safety and synergy with additional therapies - including sodium-glucose cotransporter 2 inhibitors - and clinical outcomes, positioning ASIs as an important advance in renin-angiotensin-aldosterone system modulation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.004 | 0.004 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".