{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:51:05Z","timestamp":1791456665592,"version":"4.3.4"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"Supplement_1","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Resistant and uncontrolled hypertension remain major unmet needs, with aldosterone dysregulation or frank excess increasingly recognized as a central driver. To this end, aldosterone synthase inhibitors (ASIs) represent a novel therapeutic approach targeting CYP11B2, the key enzyme responsible for aldosterone biosynthesis. By reducing aldosterone production at its source, ASIs may overcome limitations associated with conventional renin-angiotensin-aldosterone system (RAAS) blockade and attenuate both genomic and non-genomic effects of aldosterone. Advances in drug development have led to second-generation ASIs, including baxdrostat, lorundrostat, dexfadrostat, and vicadrostat, characterized by high selectivity for CYP11B2 over CYP11B1, thereby preserving cortisol synthesis. Clinical trials across phases I-III demonstrate that second-generation ASIs, including baxdrostat, lorundrostat, dexfadrostat, and vicadrostat, effectively lower aldosterone levels and produce substantial blood pressure reductions, particularly in resistant or uncontrolled hypertension. ASIs are generally well tolerated. Hyperkalemia is the most common adverse event, particularly in patients with chronic kidney disease, but is typically manageable and appears less frequent than with mineralocorticoid receptor antagonists in comparable populations. No clinically significant suppression of the hypothalamic-pituitary-adrenal axis has been observed with second-generation compounds. These findings support ASIs as a promising addition to the therapeutic armamentarium for hypertension. The recent FDA approval of baxdrostat, the first second-generation ASI, represents an important milestone for this therapeutic class. However, further studies are required to establish long-term safety, optimal patient selection, and their role in combination therapies and cardiovascular risk reduction.<\/jats:p>","DOI":"10.1093\/ajh\/hpag087","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T11:48:30Z","timestamp":1784116110000},"page":"S18-S29","source":"Crossref","is-referenced-by-count":0,"title":["Aldosterone synthase inhibitors: biological rationale, mechanism of action, and results of clinical trials"],"prefix":"10.1093","volume":"39","author":[{"given":"Stanis\u0142aw","family":"Surma","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia , Katowice,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5949-5018","authenticated-orcid":false,"given":"Krzysztof","family":"Narkiewicz","sequence":"additional","affiliation":[{"name":"Chair 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