Effectiveness of apabetalone and some other indirect epigenetic-oriented drugs in the treatment of heart failure

Epigenetic therapy for cardiovascular disease (CVD) has received increased attention from the medical community in recent years. Evidence of this is the fact that more and more controlled clinical trials evaluate the beneficial effects of: 1) direct epigenetic drugs, for example, apabetalone, and 2) repurposed drugs with possible indirect epigenetic action, for example, metformin, statins, sodium-glucose transport protein 2 (SGLT2) inhibitors and omega-3 polyunsaturated fatty acids (PUFAs) in CVD, including heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Apabetalone is the first and unique direct-acting epigenetic drug tested in patients with CVD, and the BETonMACE study showed a reduction in first hospitalization for HF (at any EF) and CVD mortality in patients with type 2 diabetes (T2D) and recent acute coronary syndrome, suggesting a possible role for this drug in secondary prevention. Patients with HFpEF appear to benefit from the addition of metformin and SGLT2 inhibitors to standard statin therapy due to their ability to reduce the death risk. In contrast, hydralazine with or without isosorbide dinitrate produced no beneficial effects. In HFrEF, metformin and SGLT2 inhibitors may reduce the risk of HF and death, while clinical trials with statins have mixed results. PUFA supplementation was associated with a significant reduction in car­diovascular risk in both HFrEF and HFpEF. However, definitive data on the benefits of direct and indirect epigenetic therapy for CVD can only be obtained from large clinical trials in the future. The purpose of this review was to provide updated information on epigenetic therapy for CVD obtained from clinical trials.