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Despite the widespread use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and mineralocorticoid receptor antagonists, \u2018aldosterone escape\u2019 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 \u201caldosterone synthase inhibitor\u201d 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 \u2013 including sodium\u2013glucose cotransporter 2 inhibitors \u2013 and clinical outcomes, positioning ASIs as an important advance in renin\u2013angiotensin\u2013aldosterone system modulation.<\/jats:p>","DOI":"10.15420\/cfr.2025.09","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T13:12:29Z","timestamp":1755609149000},"source":"Crossref","is-referenced-by-count":18,"title":["The Emerging Role of Aldosterone Synthase Inhibitors in Overcoming Renin\u2013Angiotensin\u2013Aldosterone System Therapy Limitations: A Narrative Review"],"prefix":"10.15420","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3435-8487","authenticated-orcid":false,"given":"Shubh K","family":"Patel","sequence":"first","affiliation":[{"name":"Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1036-4767","authenticated-orcid":false,"given":"Hwee","family":"Teoh","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery, St Michael\u2019s Hospital of Unity Health Toronto, Toronto, Ontario, Canada; Division of Endocrinology and Metabolism, St Michael\u2019s Hospital of Unity Health Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2083-7344","authenticated-orcid":false,"given":"Ahreni","family":"Saunthar","sequence":"additional","affiliation":[{"name":"Marlee Medical Centre, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0881-3115","authenticated-orcid":false,"given":"Terrence M","family":"Yau","sequence":"additional","affiliation":[{"name":"Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada; Division of Cardiovascular Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4018-8533","authenticated-orcid":false,"given":"Subodh","family":"Verma","sequence":"additional","affiliation":[{"name":"Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Division of Cardiac Surgery, St Michael\u2019s Hospital of Unity Health Toronto, Toronto, Ontario, Canada; Marlee Medical Centre, Toronto, Ontario, Canada; Division of Cardiovascular Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6096","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"Hu J, Zhang Z, Shen WJ, Azhar S. 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