P463 - Reduction in the Risk of Major Adverse Cardiovascular Events With Apabetalone, a Bet Protein Inhibitor, in Patients With Recent Acute Coronary Syndrome and Type 2 Diabetes According to Insulin Treatment: Analysis of the Betonmace Trial

 In Session: Cardiometabolic Treatment Approaches in Diverse Settings

Author Block: Gregory G Schwartz, Univ of Colorado Sch of Med, Aurora, CO; Stephen James Nicholls, Monash Univ, Clayton, Australia; Henry Ginsberg, Columbia Univ, New York, NY; Jan JOHANSSON, RESVERLOGIX, San Ramon, CA; Kamyar Kalantar-Zadeh, Univ of California Irvine, Orange, CA; Ewelina Kulikowski, RESVERLOGIX CORP, Calgary, AB, Canada; Peter P. Toth, CGH Medical Ctr, Rock Falls, IL; Norman Wong, RESVERLOGIX CORP, Calgary, AB, Canada; Michael Sweeney, Resverlogix Corp., Calgary, AB, Canada; Kausik K Ray, IMPERIAL COLLEGE LONDON, London, United Kingdom; On behalf of the BETonMACE investigators

Disclosure Block: G.G. Schwartz: Research Grant; Significant; Resverlogix, Roche, Sanofi. Research Grant; Modest; The Medicines Company. Other Research Support; Modest; AstraZeneca. S.J. Nicholls: Research Grant; Significant; AstraZeneca, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron and LipoScience. Honoraria; Modest; AstraZeneca, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, Boehringer Ingelheim. J. Johansson: Employment; Significant; Resverlogix. K. Kalantar-Zadeh: Honoraria; Modest; Honoraria and/or support from Abbott, Abbvie, Akebia, Alexion, Amgen, ASN (American Society of Nephrology), Astra-Zeneca, Aveo, BBraun, Chugai, Daiichi, DaVita, Fresenius, Genentech, Haymarket Media,. Other Research Support; Modest; Honoraria and/or support from Abbott, Abbvie, Akebia, Alexion, Amgen, ASN (American Society of Nephrology), Astra-Zeneca, Aveo, BBraun, Chugai, Daiichi, DaVita, Fresenius, Genentech, Haymarket Media,. E. Kulikowski: Employment; Significant; Resverlogix Corp. Stock Shareholder; Significant; Resverlogix Corp. P.P. Toth: Speaker/Speaker's Bureau; Significant; Amarin. Other; Significant; Amarin. Speaker/Speaker's Bureau; Significant; Amgen. Other; Modest; Amgen. Other; Significant; Kowa. Speaker/Speaker's Bureau; Modest; Merck. Speaker/Speaker's Bureau; Significant; Novo-Nordisk. Other; Modest; Resverlogix, Theravance. N. Wong: Employment; Significant; Resverlogix Corp. K.K. Ray: Honoraria; Modest; Daiichi Sankyo. Research Grant; Significant; Amgen, Sanofi, Regeneron, MSD, Pfizer. Honoraria; Modest; Amgen, Sanofi, Regeneron, Esperion, Medicines Company, Boehringer Ingelheim, Novo Nordisk, Kowa, Resverlogix, Dr Reddys, Cipla, Algorithm, Zuelling Pharma, Silence Therapeutics, Cerenis, Lilly, Astra Zeneca, Bayer, Akcea, MSD, Novartis. Research Grant; Significant; Daiichi Sankyo.

 Introduction: Use of insulin has been associated with worse CV outcomes in patients (pts) with type 2 diabetes T2D. Apabetalone (APB) is a novel selective inhibitor of bromodomain and extra-terminal (BET) proteins, epigenetic regulators of gene expression. In the Phase 3 BETonMACE trial treatment with APB, compared with placebo, resulted in non-significantly fewer major adverse CV events (MACE: CV death, non-fatal MI or stroke) in 2425 pts with T2D and recent acute coronary syndrome (ACS).

Objective: In this analysis of BETonMACE we examined the relationship of insulin use to MACE risk and its modification by APB.

Methods: Baseline characteristics were compared in insulin-treated (INS) or not insulin-treated (no-INS) pts. The incidence of MACE and treatment hazard ratio (HR) were compared between these two subgroups.

Results: 829 (34.2%) pts received insulin at baseline, with or without other diabetes drugs. INS vs no-INS pts were more likely to be female (29 vs 24%), had longer duration of T2D (12.6 vs 6.4 yrs), higher HbA1c (8.4 vs 6.9%) and baseline glucose (156 vs 126 mg/dL), lower use of metformin (73 vs 87%) and sulfonylureas (21 vs 33 %), and higher use of SGLT2 inhibitors (16 vs 6%) and GLP1 receptor agonists (10 vs 2%). MACE in the placebo group was higher in INS than no-INS (17.4% vs 9.7%; HR 1.94; 95% CI 1.39-2.73; p=0.0001). Overall, APB was associated with fewer MACE (HR 0.82, 95% CI 0.65-1.04, p=0.11). The relative reduction in MACE with ABP was similar in INS (HR 0.78, 95% CI. 0.55-1.10, p=0.16) and no-INS (HR 0.87, 95% CI 0.63-1.21, p = 0.42, pinteraction=0.64). The absolute reduction in MACE with APB was numerically greater among INS than non-INS (3.69 vs 1.30%).

Conclusions: Pts with T2D and recent ACS treated with insulin are at high risk for MACE. High risk of MACE with insulin use is likely through association with other clinical characteristics prognostic for MACE. Insulin treatment may be a marker to identify pts with potential for large absolute reduction in MACE with APB.