Apabetalone and hospitalization for heart failure in patients following an acute coronary syndrome: a prespecified analysis of the BETonMACE study

• Main Authors: Stephen J. Nicholls, Gregory G. Schwartz, Kevin A. Buhr, Henry N. Ginsberg, Jan O. Johansson, Kamyar Kalantar-Zadeh, Ewelina Kulikowski, Peter P. Toth, Norman Wong, Michael Sweeney, Kausik K. Ray, the BETonMACE Investigators
• Format: Article
• Language: English
• Published: BMC 2021-01-01
• Series: Cardiovascular Diabetology
• Subjects: BET inhibitors; Acute coronary syndrome; Diabetes; Heart failure; Clinical trial; Cardiovascular disease
• Online Access: https://doi.org/10.1186/s12933-020-01199-x

Abstract Background Patients with diabetes and acute coronary syndrome (ACS) are at high risk for subsequent heart failure. Apabetalone is a selective inhibitor of bromodomain and extra-terminal (BET) proteins, epigenetic regulators of gene expression. Preclinical data suggest that apabetalone exerts favorable effects on pathways related to myocardial structure and function and therefore could impact subsequent heart failure events. The effect of apabetalone on heart failure events after an ACS is not currently known. Methods The phase 3 BETonMACE trial was a double-blind, randomized comparison of apabetalone versus placebo on the incidence of major adverse cardiovascular events (MACE) in 2425 patients with a recent ACS and diabetes. This prespecified secondary analysis investigated the impact of apabetalone on hospitalization for congestive heart failure, not previously studied. Results Patients (age 62 years, 74.4% males, 90% high-intensity statin use, LDL-C 70.3 mg/dL, HDL-C 33.3 mg/dL and HbA1c 7.3%) were followed for an average 26 months. Apabetalone treated patients experienced the nominal finding of a lower rate of first hospitalization for heart failure (2.4% vs. 4.0%, HR 0.59 [95%CI 0.38–0.94], P = 0.03), total number of hospitalizations for heart failure (35 vs. 70, HR 0.47 [95%CI 0.27–0.83], P = 0.01) and the combination of cardiovascular death or hospitalization for heart failure (5.7% vs. 7.8%, HR 0.72 [95%CI 0.53–0.98], P = 0.04). Conclusion Apabetalone treatment was associated with fewer hospitalizations for heart failure in patients with type 2 diabetes and recent ACS. Future studies are warranted to define the potential for BET inhibition with apabetalone to prevent heart failure in patients with diabetes and ACS.