{
  "abstract": "BACKGROUND: Aldosterone synthase inhibitors (ASIs) have emerged as a mechanistically targeted strategy for resistant and uncontrolled hypertension; however, no head-to-head trials exist, and comparative efficacy and safety remain uncertain. We compared their efficacy and safety using network and pairwise meta-analysis of randomized trials. METHODS: This systematic review and meta-analysis adhered to the PRISMA guidelines. PubMed/MEDLINE, Scopus, Embase, ClinicalTrials.gov, and Cochrane Library were searched from inception to January 14, 2026, for randomized trials evaluating ASIs versus placebo or standard care. A frequentist random-effects network meta-analysis assessed systolic (SBP) and diastolic blood pressure (DBP). Dichotomous safety outcomes were pooled using Hartung-Knapp random-effects models. Network consistency was evaluated using design-by-treatment interaction modeling. Prespecified subgroup analyses stratified outcomes by hypertension phenotype (resistant vs uncontrolled). RESULTS: Across 7 RCTs (n = 2,828), all ASIs significantly reduced SBP versus placebo: baxdrostat -8.63 mmHg (95% CI -10.84 to -6.42), lorundrostat -7.47 mmHg (95% CI -9.54 to -5.40), and LCI699/osilodrostat -5.63 mmHg (95% CI -9.15 to -2.12), with no significant indirect differences between agents. In resistant hypertension, lorundrostat (-9.00 mmHg; 95% CI -13.19 to -4.81) and baxdrostat (-8.77 mmHg; 95% CI -10.50 to -7.05) demonstrated pronounced reductions. In uncontrolled hypertension, LCI699/osilodrostat showed the largest point estimate (-10.55 mmHg; 95% CI -16.49 to -4.61), though this derives from a single early-phase trial and requires cautious interpretation. DBP reductions were significant for baxdrostat (-3.23 mmHg; 95% CI -4.73 to -1.73) and lorundrostat (-3.60 mmHg; 95% CI -5.43 to -1.77). Hypotension (RR 2.67), hyperkalemia (RR 7.94), and hyponatremia (RR 2.07) were significantly increased; serious adverse events, discontinuation, and network inconsistency were not detected. CONCLUSIONS: ASIs provide clinically meaningful BP reduction across both hypertension phenotypes; however, short-term use is associated with hypotension and electrolyte disturbances, necessitating careful monitoring. Phenotype-specific efficacy and long-term safety require validation in outcome-driven trials. Systematic Review Registration: PROSPERO CRD420251266257.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Internal Medicine, Guthrie Robert Packer Hospital, Sayre, Pennsylvania, United States of America",
    "Division of CardioNephrology, Cardiac Renal & Vascular Associates, Jackson, Mississippi, United States of America",
    "Department of Medicine, University of Calabar, Calabar, Nigeria",
    "Department of Epidemiology, Yale School of Public Health, New Haven, Connecticut, United States of America",
    "Department of Medicine, Obafemi Awolowo University, Ile-Ife, Nigeria"
  ],
  "article_type": "review",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ismaila Ajayi Yusuf",
      "orcid": "0009-0002-2319-3899"
    },
    {
      "affs": [
        1
      ],
      "name": "Olurotimi J. Badero",
      "orcid": "0009-0001-2401-6117"
    },
    {
      "affs": [
        2
      ],
      "name": "Alozie Ihesiulo",
      "orcid": "0009-0006-8313-6350"
    },
    {
      "affs": [
        3
      ],
      "name": "Micah Nnabuko Okwah",
      "orcid": "0009-0004-6023-1756"
    },
    {
      "affs": [
        4
      ],
      "name": "Abieyuwa Tari-Ere Oshodin",
      "orcid": "0009-0001-2369-5365"
    },
    {
      "affs": [
        2
      ],
      "name": "Emmanuella Asikong",
      "orcid": "0009-0006-7790-6259"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/087mwb44c5kfx.bib",
  "cited_by": 10,
  "doi": "10.1371/journal.pone.0349932",
  "fulltext_url": null,
  "id": "087mwb44c5kfx",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0349932",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2712|Hormonal Regulation and Hypertension"
    ]
  ],
  "openalex": "W7163333725",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0349932&type=printable",
  "pmcid": "PMC13232938",
  "pmid": "42234700",
  "published": "2026-06-03",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/087mwb44c5kfx.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T13:21:08Z",
      "native_id": "W7163333725",
      "source": "openalex",
      "url": "https://doi.org/10.1371/journal.pone.0349932"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2712|Hormonal Regulation and Hypertension",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "Aldosterone synthase inhibitors in uncontrolled and resistant hypertension: A phenotype-stratified systematic review and network meta-analysis of randomized trials",
  "title_text": "Aldosterone synthase inhibitors in uncontrolled and resistant hypertension: A phenotype-stratified systematic review and network meta-analysis of randomized trials",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T13:20:39Z",
  "url": "https://research.draconitic.com/paper/087mwb44c5kfx",
  "venue": "PLoS ONE",
  "versions": []
}