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

• Hypertension and Vascular Disease: From the Lab to Trials
  October 24, 2020 | Location: Simulive
  Abstract Time: 05:00 PM - 07:00 PM

Category: Hypertension and CVD

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

Authors

• Kalantar-Zadeh, Kamyar, University of California Irvine, Irvine, California, United States

Kamyar Kalantar-Zadeh, MD, DrMed, PhD, MPH, FASN



Dr Kam Kalantar-Zadeh is a practicing triple-board certified Nephrologist in Southern California and Nephrology chief at the University of California Irvine (UCI). Kalantar has ongoing research and has published extensively on CKD and ESRD.

• Schwartz, Gregory G., University of Colorado Denver School of Medicine, Aurora, Colorado, United States

Gregory G. Schwartz,

• Buhr, Kevin A., Statistical Data Analysis Center, University of Wisconsin-Madison, Madison, Wisconsin, United States

Kevin A. Buhr,

• Ginsberg, Henry N., Columbia University, New York, New York, United States

Henry N. Ginsberg,

• Johansson, Jan O., Resverlogix Corp., San Francisco, California, United States

Jan O. Johansson,

• Kulikowski, Ewelina, Resverlogix Corp., Calgary, Alberta, Canada

Ewelina Kulikowski,

• Nicholls, Stephen J., Monash Cardiovascular Research Centre, Monash University, Melbourne, Victoria, Australia

Stephen J. Nicholls,

• Toth, Peter Paul, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

Peter Paul Toth,

• Wong, Norman Cw, Resverlogix Corp., Calgary, Alberta, Canada

Norman Cw Wong,

• Sweeney, Michael, Resverlogix Corp., San Francisco, California, United States

Michael Sweeney,

• Ray, Kausik K., Imperial Centre for Cardiovascular Disease Prevention, Imperial College London, London, United Kingdom

Kausik K. Ray,

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.