ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

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

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

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

Authors

  • 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
Background

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.

Methods

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).

Results

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.

Conclusion

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.