{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:12:47Z","timestamp":1783930367521,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) is a progressive and life-threatening condition characterized by elevated pulmonary vascular resistance eventually causing right ventricular failure and premature death. Despite advances in targeted therapies, morbidity and mortality levels remain high, highlighting the need for additional treatment strategies that address the disease\u2019s multifactorial pathophysiology. Attention has recently centred on two pharmacological groups with proven roles in other cardiovascular settings: sodium\u2013glucose cotransporter 2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists (MRAs). SGLT2 inhibitors have demonstrated robust clinical benefits in heart failure (HF), type 2 diabetes mellitus (T2DM), and chronic kidney disease (CKD), extending survival and reducing hospitalizations. Although their primary actions involve renal glucose and sodium handling, accumulating evidence suggests they may also exert favourable effects on the pulmonary vasculature, endothelial function, and right ventricular performance. In parallel, elevated aldosterone levels have been implicated in vascular remodelling, inflammation, and fibrosis in PAH, suggesting a potential therapeutic role for MRAs. However, the strength and clinical significance of these associations remain under investigation. The aim of this review is to synthesize and critically appraise the current evidence regarding the potential role of SGLT2 inhibitors and MRAs in the treatment of pulmonary arterial hypertension, exploring their mechanistic rationale, preclinical findings, and available clinical data to determine whether these agents may offer additional therapeutic benefit in PAH management.<\/jats:p>","DOI":"10.3390\/medicina62071345","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T07:28:27Z","timestamp":1783927707000},"page":"1345","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Repurposing Heart Failure Therapies in Pulmonary Arterial Hypertension: Mechanistic Rationale, Translational Evidence, and Clinical Perspectives for SGLT2 Inhibitors and Mineralocorticoid Receptor Antagonists"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4755-8607","authenticated-orcid":false,"given":"Spyridon","family":"Karkoulias","sequence":"first","affiliation":[{"name":"First Cardiology Department, General Hospital of Nikea, Agios Panteleimon Piraeus, 3 D. Mantouvalou Street, 18454 Piraeus, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6992-2906","authenticated-orcid":false,"given":"Ioannis","family":"Leontsinis","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5768-9125","authenticated-orcid":false,"given":"Panagiotis","family":"Iliakis","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, 11527 Athens, Greece"},{"name":"Division of Cardiology, Angiology and Internal Emergency Medicine, Department of Medicine, Knappschaft Kliniken University Hospital Bochum, Ruhr University Bochum, 44892 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7044-2931","authenticated-orcid":false,"given":"Liza","family":"Kallenou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, KAT General Hospital, 14561 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros","family":"Tsiavos","sequence":"additional","affiliation":[{"name":"First Cardiology Department, General Hospital of Nikea, Agios Panteleimon Piraeus, 3 D. 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