Highlights from

AHA 2019

American Heart Association’s Scientific Sessions

Philadelphia, USA 16 - 18 November 2019

Phase 3 BETonMACE Trial Did Not Meet Its Primary Endpoint

Apabetalone does not decrease cardiovascular (CV) death, non-fatal myocardial infarction (MI), or stroke compared with placebo in diabetic patients with recent acute coronary syndrome (ACS).

Prof. Kausik K. Ray (Imperial College London, United Kingdom) presented the phase 3, international, multi-centre, randomised, double-blind, placebo-controlled BETonMACE trial, which is the first study to explore whether epigenetic modulation with the selective bromodomain and extra-terminal (BET) protein inhibitor apabetalone is safe and effective in reducing CV risk [1].

Apabetalone, a BET inhibitor that selectively targets bromodomain 2 (BD2), was compared with standard of care therapy in patients with type 2 diabetes mellitus (T2DM) and low HDL-C after acute coronary syndrome (ACS).

The primary outcome of the study was time to CV death or non-fatal myocardial infarction or non-fatal stroke, with a secondary outcome of time to CV death or non-fatal MI or non-fatal stroke or unstable angina or emergency revascularisation. Inclusion criteria comprised patients with ACS in the preceding 7-90 days, T2DM, and HDL-C ≤40 mg/dl for men, ≤45 mg/dl for women.

The median age of participants was 62 years, 25% females. At baseline, MI was the index ACS event in 74% (STEMI 53%, NSTEMI 47%) of patients, with unstable angina constituting 26%. Patients had a median LDL-C 65 mg/dl, HDL-C 33 mg/dl, and HbA1c 7.3% at time of enrolment. The median follow-up was 26 months.

Enrolled between November 2015 and July 2018 at 195 sites across 13 countries, a total of 2,425 patients were randomised to receive apabetalone 100 mg orally twice daily or matching placebo (1:1) on top of guideline-recommended standard of care including intensive or maximum-tolerated treatment with atorvastatin or rosuvastatin.

Apabetalone changed HDL-C from baseline at 100 weeks by 16.2% versus 10.4% (P=0.001). However, the primary outcome for apabetalone (n=1212) compared with placebo (n=1206) was 10.3% versus 12.4% (P=0.11), the rate of cardiovascular death/MI was 9.2% versus 11.5% (P>0.05), the rate of stroke was 1.4% versus 1.4% (P>0.05), the all-cause mortality rate was 5.0% versus 5.7% (P>0.05), and the change in LDL-C from baseline at 100 weeks 11.5% versus 14.9% (P=0.35).

The rate of adverse events was similar across treatment groups, with 830 patients (68.5%) in the apabetalone arm and 820 (67.9%) in the placebo arm reporting at least 1 adverse event.

  1. Ray KK, et al. Effect of BET Protein Inhibition With Apabetalone on Cardiovascular Outcomes in Patients With Acute Coronary Syndrome and Diabetes - Results of the BETonMACE Trial. Session LBS01. American Heart Association Annual Scientific Sessions (AHA 2019), 14-18 November, Philadelphia, PA, USA.

Top image: @ iStockPhoto: Noctiluxx

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