Reduction in the risk of major adverse cardiovascular events with the BET protein inhibitor apabetalone in patients with recent acute coronary syndrome, type 2 diabetes, and moderate to high likelihood of non-alcoholic fatty liver disease.

Background

Nonalcoholic fatty liver disease (NAFLD) is common among patients with type 2 diabetes mellitus (T2DM) and is associated with increased risk for coronary atherosclerosis and acute cardiovascular (CV) events. We employed the validated, non-invasive Angulo NAFLD fibrosis score (FS) in an intervention study in patients with T2DM and recent acute coronary syndrome (ACS) to determine the association of FS with CV risk and treatment response to apabetalone. Apabetalone is a novel selective inhibitor of the second bromodomain of bromodomain and extra-terminal (BET) proteins, epigenetic regulators of gene expression.

Methods

The Phase 3 BETonMACE trial compared apabetalone with placebo in 2,425 patients with T2DM and recent ACS. In this

Results

In 73.7% of patients, FS was elevated and consistent with a moderate-to-high likelihood of advanced liver fibrosis (FS+); 26.3% of patients had a lower FS (FS

Conclusions

Amongst patients with T2DM, recent ACS, and a moderate-to-high likelihood of advanced liver fibrosis, apabetalone was associated with a significantly lower rate of ischemic MACE and HHF and attenuated the increase in hepatic FS over time.

Informations de copyright

© 2022 The Authors. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

GGS has received research support to the University of Colorado from AstraZeneca, Resverlogix, Roche, Sanofi, and The Medicines Company. He is coinventor of pending US patent 62/806,313 (“Methods for Reducing Cardiovascular Risk”) assigned in full to the University of Colorado. SJN reports research grants from AstraZeneca, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron and LipoScience and honoraria from AstraZeneca, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, Boehringer Ingelheim. PPT reports speaker bureau compensation from Amgen, Esperion, Novo-Nordisk; consultant compensation from Amarin, Amgen, Kowa, and Novartis. AK, JJ, EK, MS, and NCWW are employees of Resverlogix Corporation. KKZ has received honoraria from Abbott, Abbvie, ACI Clinical, Akebia, Alexion, Amgen, Ardelyx, Astra-Zeneca, Aveo, Braun, Cara Therapeutics, Chugai, Cytokinetics, Daiichi, DaVita, Fresenius, Genentech, Haymarket Media, Hospira, Kabi, Keryx, Kissei, Novartis, Pfizer, Regulus, Relypsa, Resverlogix, Dr. Schaer, Sandoz, Sanofi, Shire, Vifor, UpToDate, and ZS-Pharma. HNG has received research support from AstraZeneca, Amgen, Pfizer and honoraria from Astrazeneca, Amgen, Pfizer, Merck, Kowa, Resverlogix, Regeneron, Sanofi. KKR reports honoraria from Resverlogix, Aegerion, Amgen, Pfizer, AstraZeneca, Cerenis, Akcea, The Medicines Company, Kowa, Novartis, Cipla, Eli Lilly, Algorithm, Takeda, Boehringer Ingelheim, Abbvie, Silence Therapeutics, Dr. Reddys, Bayer, Daiichi Sankyo, Esperion, Zuelling Pharma, Sanofi-Regeneron and Merck and grants from Sanofi-Regeneron and Merck.