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This hemodynamic strain forces the right ventricle to pump against a high\u2010pressure system, ultimately leading to right\u2010sided heart failure and death. The pathogenesis of PAH involves a complex interplay of vasoconstriction, chronic inflammation, and pathological remodeling of the pulmonary vessel walls\u2014specifically hypertrophy of the smooth muscle and intimal layers\u2014driven by molecular imbalances and genetic predispositions. Current FDA\u2010approved therapies primarily manage symptoms through vasodilation but fail to directly target the underlying vascular remodeling. Imatinib, a tyrosine kinase inhibitor originally developed for oncological indications, has emerged as a potential disease\u2010modifying agent for PAH. By inhibiting platelet\u2010derived growth factor receptors (PDGFR), imatinib targets the aberrant proliferation of smooth muscle cells, offering a mechanism to potentially reverse or arrest vascular remodeling. Clinical trials, including the IMPRES study, have demonstrated encouraging hemodynamic improvements in patients with severe PAH refractory to standard therapies. However, systemic safety concerns and dose\u2010dependent adverse reactions have limited its clinical approval. This review examines the pharmacological rationale for imatinib, its impact on vascular structure, and the safety signals observed in long\u2010term studies. Furthermore, it discusses emerging strategies, such as inhaled formulations and pharmacogenetic approaches (e.g., the PIPAH study), aimed at enhancing the efficacy\u2010to\u2010safety ratio of kinase inhibitors to improve long\u2010term outcomes for patients with PAH.<\/jats:p>","DOI":"10.1002\/iub.70098","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T10:29:41Z","timestamp":1774520981000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Future Prospects of Imatinib in Advanced Pulmonary Hypertension Management"],"prefix":"10.1002","volume":"78","author":[{"given":"Federica","family":"Dav\u00ec","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina  Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stella","family":"Mangione","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliera Universitaria Policlinico AOU G. 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