Rewriting heart health: epigenetic drugs in cardiovascular medicine

Cardiovascular disease reflects not only genetic pre-disposition and haemodynamic stress but also reversible alterations in chromatin organization and transcriptional programming, a layer of regulation that is, in principle, amenable to pharmacological intervention. 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–angiotensin–aldosterone system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, antithrombotic agents, sodium–glucose cotransporter-2 inhibitors, and incretin-based therapies, appear to modulate the epigenome as an underappreciated component of their action, a concept termed ‘pharmaco-epigenetics’. 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.