ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2020 and some content may be unavailable. To unlock all content for 2020, please visit the archives.

Abstract: SA-OR40

Effect of Apabetalone on Major Adverse Cardiovascular Events in Patients with CKD, Diabetes, and Recent Acute Coronary Syndrome: Results from the BETonMACE Trial

Session Information

Category: Hypertension and CVD

  • 1402 Hypertension and CVD: Clinical, Outcomes, and Trials


  • Kalantar-Zadeh, Kamyar, University of California Irvine, Irvine, California, United States
  • Schwartz, Gregory G., University of Colorado Denver School of Medicine, Aurora, Colorado, United States
  • Buhr, Kevin A., Statistical Data Analysis Center, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Ginsberg, Henry N., Columbia University, New York, New York, United States
  • Johansson, Jan O., Resverlogix Corp., San Francisco, California, United States
  • Kulikowski, Ewelina, Resverlogix Corp., Calgary, Alberta, Canada
  • Nicholls, Stephen J., Monash Cardiovascular Research Centre, Monash University, Melbourne, Victoria, Australia
  • Toth, Peter Paul, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Wong, Norman Cw, Resverlogix Corp., Calgary, Alberta, Canada
  • Sweeney, Michael, Resverlogix Corp., San Francisco, California, United States
  • Ray, Kausik K., Imperial Centre for Cardiovascular Disease Prevention, Imperial College London, London, United Kingdom

Group or Team Name

  • BETonMACE Investigators

Chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) patients (pts) is associated with increased cardiovascular disease (CVD) and heart failure risk. We hypothesized that a maladaptive epigenetic response engaging the bromodomain and extraterminal (BET) protein transcription system contributes to excess CVD risk. Hence, the efficacy of BET inhibition (BETi) treatment with apabetalone (APB) was assessed according to presence of CKD in the phase 3 BETonMACE trial.


BETonMACE compared APB with placebo in 2425 pts with T2DM and recent acute coronary syndrome. The primary outcome was CV death, non-fatal myocardial infarct or stroke (MACE). Hospitalization for congestive heart failure (HCHF) was a secondary endpoint. Both outcomes were evaluated according to the presence of CKD (estimated GFR <60 mL/min/1.73 m2 at baseline).


CKD pts were older (71 vs. 61 years), more likely female (42% vs. 23%) or non-white (18% vs. 12%), had longer duration of diabetes (mean 11.3 vs. 8.2 years) and higher serum alkaline phosphatase (91 vs. 81 U/L), and were less likely to receive metformin (69% vs. 84%) or SGLT2 inhibitors (6% vs. 13%) (P<0.05 for all). Under placebo, risk of endpoints was higher in CKD vs. non-CKD pts [MACE: 35/164 (21.3%) vs.114/1041 (11.0%), HR=2.40, 95% CI [1.67, 3.44]; HCHF: 14/164 (8.5%) vs. 34/1041 (3.3%), HR=3.19, 95% CI [1.66,6.12]; P<0.001 for both). Under APB treatment, pts with CKD had significant reductions in MACE (HR=0.50, 95% CI [0.26, 0.96], P=0.034) and HCHF (HR=0.26, 95% CI [0.07,0.94], P=0.028) vs. placebo, see Kaplan-Meier figures.


CKD patients with T2DM and recent acute coronary syndrome have a high risk of MACE that was substantially reduced with APB BETi in the phase 3 BETonMACE trial.