PMID- 34079271
OWN - NLM
STAT- MEDLINE
DCOM- 20210708
LR  - 20210708
IS  - 1178-2048 (Electronic)
IS  - 1176-6344 (Print)
IS  - 1176-6344 (Linking)
VI  - 17
DP  - 2021
TI  - Epigenetic Therapies for Heart Failure: Current Insights and Future Potential.
PG  - 247-254
LID - 10.2147/VHRM.S287082 [doi]
AB  - Despite the current reductionist approach providing an optimal indication for 
      diagnosis and treatment of patients with heart failure with reduced ejection 
      fraction (HFrEF), there are no standard pharmacological therapies for heart 
      failure with preserved ejection fraction (HFpEF). Although in its infancy in 
      cardiovascular diseases, the epigenetic-based therapy ("epidrugs") is capturing 
      the interest of physician community. In fact, an increasing number of controlled 
      clinical trials is evaluating the putative beneficial effects of: 1) direct 
      epigenetic-oriented drugs, eg, apabetalone, and 2) repurposed drugs with a 
      possible indirect epigenetic interference, eg, metformin, statins, sodium glucose 
      transporter inhibitors 2 (SGLT2i), and omega 3 polyunsaturated fatty acids 
      (PUFAs) in both HFrEF and HFpEF, separately. Apabetalone is the first and unique 
      direct epidrug tested in cardiovascular patients to date, and the BETonMACE trial 
      has reported a reduction in first HF hospitalization (any EF value) and 
      cardiovascular death in patients with type 2 diabetes and recent acute coronary 
      syndrome, suggesting a possible role in secondary prevention. Patients with HFpEF 
      seem to benefit from supplementation to the standard therapy with statins, 
      metformin, and SGLT2i owing to their ability in reducing mortality. In contrast, 
      the vasodilator hydralazine, with or without isosorbide dinitrate, did not 
      provide beneficial effects. In HFrEF, metformin and SGLT2i could reduce the risk 
      of incident HF and mortality in affected patients whereas clinical trials based 
      on statins provided mixed results. Furthermore, PUFAs diet supplementation was 
      significantly associated with reduced cardiovascular risk in both HFpEF and 
      HFrEF. Future large trials will reveal whether direct and indirect epitherapy 
      will remain a work in progress or become a useful way to customize the therapy in 
      the real-world management of HFpEF and HFrEF. Our goal is to discuss the recent 
      advancement in the epitherapy as a possible way to improve personalized therapy 
      of HF.
CI  - (c) 2021 Napoli et al.
FAU - Napoli, Claudio
AU  - Napoli C
AD  - Department of Advanced Medical and Surgical Sciences (DAMSS), University of 
      Campania "Luigi Vanvitelli", Naples, 80138, Italy.
FAU - Bontempo, Paola
AU  - Bontempo P
AD  - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 
      Naples, 80138, Italy.
FAU - Palmieri, Vittorio
AU  - Palmieri V
AD  - Department of Cardiac Surgery and Transplantation, Heart Transplantation Unit in 
      Adults of the 'Ospedali dei Colli Monaldi-Cotugno-CTO', Naples, Italy.
FAU - Coscioni, Enrico
AU  - Coscioni E
AUID- ORCID: 0000-0002-4373-3760
AD  - Department of Cardiac Surgery, Azienda Ospedaliera Universitaria San Giovanni di 
      Dio e Ruggi d'Aragona, Salerno, Italy.
FAU - Maiello, Ciro
AU  - Maiello C
AD  - Department of Cardiovascular Surgery and Transplants, Monaldi Hospital, Azienda 
      dei Colli, Naples, Italy.
FAU - Donatelli, Francesco
AU  - Donatelli F
AUID- ORCID: 0000-0003-2839-0373
AD  - Chair of Cardiac Surgery, Department of Cardiothoracic Center, Istituto Clinico 
      Sant'Ambrogio, University of Milan, Milan, Italy.
FAU - Benincasa, Giuditta
AU  - Benincasa G
AD  - Department of Advanced Medical and Surgical Sciences (DAMSS), University of 
      Campania "Luigi Vanvitelli", Naples, 80138, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210524
PL  - New Zealand
TA  - Vasc Health Risk Manag
JT  - Vascular health and risk management
JID - 101273479
RN  - 0 (Cardiovascular Agents)
RN  - 0 (Quinazolinones)
RN  - 8R4A7GDZ1D (apabetalone)
SB  - IM
MH  - Cardiovascular Agents/adverse effects/*therapeutic use
MH  - *Drug Repositioning
MH  - Epigenesis, Genetic/*drug effects
MH  - Heart Failure/*drug therapy/genetics/physiopathology
MH  - Humans
MH  - Quinazolinones/adverse effects/*therapeutic use
MH  - Treatment Outcome
PMC - PMC8164213
OTO - NOTNLM
OT  - epidrugs
OT  - heart failure
OT  - personalized therapy
COIS- The authors report no conflicts of interest in this work.
EDAT- 2021/06/04 06:00
MHDA- 2021/07/09 06:00
PMCR- 2021/05/24
CRDT- 2021/06/03 06:37
PHST- 2021/03/18 00:00 [received]
PHST- 2021/04/29 00:00 [accepted]
PHST- 2021/06/03 06:37 [entrez]
PHST- 2021/06/04 06:00 [pubmed]
PHST- 2021/07/09 06:00 [medline]
PHST- 2021/05/24 00:00 [pmc-release]
AID - 287082 [pii]
AID - 10.2147/VHRM.S287082 [doi]
PST - epublish
SO  - Vasc Health Risk Manag. 2021 May 24;17:247-254. doi: 10.2147/VHRM.S287082. 
      eCollection 2021.