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Purpose-built epigenetic drugs, DNA methyltransferase inhibitors, histone deacetylase inhibitors, histone acetyltransferase inhibitors, bromodomain and extra-terminal domain inhibitors, enhancer of zeste homolog 2 inhibitors, and RNA-based therapeutics, target this machinery directly. In parallel, established cardiovascular therapies, including statins, renin\u2013angiotensin\u2013aldosterone system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, antithrombotic agents, sodium\u2013glucose cotransporter-2 inhibitors, and incretin-based therapies, appear to modulate the epigenome as an underappreciated component of their action, a concept termed \u2018pharmaco-epigenetics\u2019. This review appraises both axes side by side, with explicit attention to clinical maturity, including the level of evidence, human validation, development stage, and the interpretation of hypothesis-generating findings. Key translational barriers, cardiac-targeted delivery, biomarkers of target engagement, and interindividual epigenetic variability, are outlined alongside priorities for future trial design.<\/jats:p>","DOI":"10.1093\/ehjcvp\/pvag075","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:54:20Z","timestamp":1789041260000},"page":"512-528","source":"Crossref","is-referenced-by-count":1,"title":["Rewriting heart health: epigenetic drugs in cardiovascular medicine"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7793-7082","authenticated-orcid":false,"given":"Natalia","family":"Atzemian","sequence":"first","affiliation":[{"name":"Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of Zurich , Wagistrasse 12, Schlieren, 8952 ,","place":["Switzerland"]},{"name":"Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich , Zurich, R\u00e4mistrasse 100, 8091 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1941-6938","authenticated-orcid":false,"given":"Ludovica","family":"Di Venanzio","sequence":"additional","affiliation":[{"name":"Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of Zurich , Wagistrasse 12, Schlieren, 8952 ,","place":["Switzerland"]},{"name":"Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich , Zurich, R\u00e4mistrasse 100, 8091 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2365-5037","authenticated-orcid":false,"given":"Shafeeq Ahmed","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of Zurich , Wagistrasse 12, Schlieren, 8952 ,","place":["Switzerland"]},{"name":"Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich , Zurich, R\u00e4mistrasse 100, 8091 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Costantino","sequence":"additional","affiliation":[{"name":"Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of Zurich , Wagistrasse 12, Schlieren, 8952 ,","place":["Switzerland"]},{"name":"Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich , Zurich, R\u00e4mistrasse 100, 8091 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Ruschitzka","sequence":"additional","affiliation":[{"name":"Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of Zurich , Wagistrasse 12, Schlieren, 8952 ,","place":["Switzerland"]},{"name":"Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich , Zurich, R\u00e4mistrasse 100, 8091 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6483-7844","authenticated-orcid":false,"given":"Francesco","family":"Paneni","sequence":"additional","affiliation":[{"name":"Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, Zurich University Hospital, University of Zurich , Wagistrasse 12, Schlieren, 8952 ,","place":["Switzerland"]},{"name":"Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich , Zurich, R\u00e4mistrasse 100, 8091 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