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Physiological changes, due to biological ageing and frailty in the presence of multiple chronic conditions and polypharmacy can limit optimisation of pharmacotherapy due to the increased risk of severe adverse events, leading to poorer outcomes in individuals with HF. While our understanding of the impact of frailty on HF aetiology and treatments is still emerging, HF may contribute to or worsen symptoms of frailty. This narrative review describes the interactions between clinical pharmacology and frailty and how to consider these in HF management. We examine the impact of physiological changes in HF and frailty on pharmacodynamics, pharmacokinetics effectiveness and safety of HF pharmacotherapy in men and women. There are significant opportunities to integrate frailty assessment in emerging research and models of care for HF.<\/jats:p>","DOI":"10.15420\/ecr.2025.42","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T13:56:30Z","timestamp":1782222990000},"source":"Crossref","is-referenced-by-count":1,"title":["Clinical Pharmacology of Heart Failure in Frailty"],"prefix":"10.15420","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6764-3233","authenticated-orcid":false,"given":"Mai H","family":"Duong","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0384j8v12","id-type":"ROR","asserted-by":"publisher"}],"name":"The University of Sydney"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0735-9756","authenticated-orcid":false,"given":"Martha","family":"Gulati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7474-3737","authenticated-orcid":false,"given":"Parag","family":"Goyal","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r109517","id-type":"ROR","asserted-by":"publisher"}],"name":"Weill Cornell Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8068-2440","authenticated-orcid":false,"given":"Shaun G","family":"Goodman","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03dbr7087","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Toronto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8299-9871","authenticated-orcid":false,"given":"Julee","family":"McDonagh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jtmb277","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Wollongong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5970-1501","authenticated-orcid":false,"given":"Sarah","family":"Hilmer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02gs2e959","id-type":"ROR","asserted-by":"publisher"}],"name":"Royal North Shore Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6096","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref0","doi-asserted-by":"crossref","unstructured":"Clegg A, Young J, Iliffe S, et al. 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