Cardiovascular effects of histone deacetylase inhibitors epigenetic therapies: Systematic review of 62 studies and new hypotheses for future research

Background Epigenetic regulation by Histone Deacetylases (HDACs) plays an important role in multiple pathophysiological processes, including tumor growth and cardiovascular diseases. HDAC inhibitors (HDACi) have emerged as important therapeutic agents for multiple human cancers, and several randomized clinical trials have been recently undertaken to test their safety and efficacy in cancer patients. Although HDACi have shown beneficial effects in several preclinical models of cardiovascular diseases, concerns have emerged regarding their potential cardiac toxic effects. The present study assessed the extent and possible significance of cardiovascular adverse effects induced by HDACi administration. Methods and results Based on the available published clinical trials reporting cardiovascular effects of HDACi therapy in cancer patients, 62 studies for a total patient population of 3268 were included to perform a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) requirements. A further analysis was conducted to evaluate cardiovascular effects of the different drugs among the HDACi class. Overall, only a minority of studies reported cardiovascular effect of HDACi, and showed mild but frequent cardiovascular side effects after HDACi treatment in cancer patients. Conclusions Future studies will be required to better determine the role and the mechanisms underlying cardiovascular effects of HDACi in the context of oncological therapy and beyond.