The Effect of Bromodomain and Extra-Terminal Inhibitor Apabetalone on Attenuated Coronary Atherosclerotic Plaque: Insights from the ASSURE Trial

American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions
Daisuke ShishikuraStephen J Nicholls

Abstract

Apabetalone is a selective bromodomain and extra-terminal (BET) inhibitor which modulates lipid and inflammatory pathways implicated in atherosclerosis. The impact of apabetalone on attenuated coronary atherosclerotic plaque (AP), a measure of vulnerability, is unknown. The ApoA-1 Synthesis Stimulation and intravascular Ultrasound for coronary atheroma Regression Evaluation (ASSURE; NCT01067820) study employed serial intravascular ultrasound (IVUS) measures of coronary atheroma in 281 patients treated with apabetalone or placebo for 26 weeks. AP was measured at baseline and follow-up. Factors associated with changes in AP were investigated. AP was observed in 31 patients (11%) [27 (13.0%) in the apabetalone group and four (5.5%) in the placebo group]. The apabetalone group demonstrated reductions in AP length by - 1 mm [interquartile range (IQR) - 4, 1] (p = 0.03), AP arc by - 37.0° (IQR - 59.2, 8.2) (p = 0.003) and the AP index by - 34.6 mm° (IQR - 52.6, 10.1) (p = 0.003) from baseline. The change in AP index correlated with on-treatment concentration of high-density lipoprotein (HDL) particles (r = - 0.52, p = 0.006), but not HDL cholesterol (r = - 0.11, p = 0.60) or apolipoprotein A-1 (r = - 0.16, p = 0.43). Multivariable an...Continue Reading

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Citations

May 8, 2020·Future Cardiology·Julia Brandts, Kausik K Ray
May 2, 2020·Expert Opinion on Therapeutic Targets·Federico CarboneAmirhossein Sahebkar
Aug 19, 2020·Antioxidants & Redox Signaling·Stefano MasiSarah Costantino
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Jul 3, 2021·International Journal of Molecular Sciences·Talha Ijaz, Michael A Burke

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