P1437 - Cardiovascular Benefits of Apabetalone: A Meta-analysis

In Session: Impact of Treatment Interventions on Stable Coronary Artery Disease

Author Block: Hang Long Li, Qi Feng, Yue Fei, bernard cheung, The Univ of Hong Kong, Hong Kong, Hong Kong

Disclosure Block: H. Li: None. Q. Feng: None. Y. Fei: None. B. cheung: None.

Introduction: Apabetalone is a novel drug that reduces inflammation and thrombosis by inhibiting bromodomain and extra-terminal proteins (BET). Three phase II trials suggested benefits whereas the recent phase III BETonMACE trial did not. To reconcile these differences, we performed a meta-analysis of all trials on apabetalone.

Methods: MEDLINE, EMBASE, Cochrane Library, and ClinialTrials.gov were searched for randomized controlled trials of apabetalone up to May 05, 2020. The outcomes of interest were major adverse cardiovascular events (MACE) and hospitalization for heart failure. The secondary outcomes were death, myocardial infarction (MI), coronary revascularization, high-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I). Pooled risk ratios (RRs) or mean differences (MD) in a fixed-effects model were generated using the “meta” package in R (version 3.6.3).

Results: Four trials (median follow-up 3-26.5 months) with altogether 3223 patients were included. All patients had coronary artery disease and received standard statin therapy. Apabetalone significantly reduced MACE (RR 0.78, 95% CI: 0.63-0.96) and hospitalization for heart failure (RR 0.48, 95% CI: 0.33-0.70) compared to placebo (Fig.). No significant differences were observed for death (RR 0.87, 95% CI: 0.63-1.21), MI (RR 0.82, 95% CI: 0.62-1.10), or coronary revascularization (RR 0.67, 95% CI: 0.31-1.49). Apabetalone increased ApoA-I (MD 2.82%, 95% CI: 1.36-4.28) and HDL (MD 0.04%, 95% CI: 0.02-0.07). Conclusions: Although the BETonMACE trial failed to demonstrate significant benefits, our meta-analysis shows that apabetalone reduces MACE and hospitalization for heart failure in patients with coronary artery disease. Larger outcome trials are urgently needed to investigate the benefits of epigenetic modulation through BET protein inhibition.