Kausik K Ray1, Stephen J Nicholls2, Henry D Ginsberg3, Jan O Johansson4, Kamyar Kalantar-Zadeh5, Ewelina Kulikowski4, Peter P Toth6, Norman Wong4, Jeffrey L Cummings7, Michael Sweeney4, Gregory G Schwartz8. 1. Imperial Centre for Cardiovascular Disease Prevention, Imperial College, London, UK. Electronic address: k.ray@imperial.ac.uk. 2. MonashHeart, Monash University, Melbourne, Australia. 3. Irving Institute for Clinical and Translational Research, Columbia University, New York, NY. 4. Resverlogix Corporation, Calgary, Alberta, Canada. 5. Division of Nephrology and Hypertension, University of California Irvine. 6. CGH Medical Center Sterling, Illinois, and Cicarrone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland. 7. Neurological Institute, Cleveland Clinic Lerner School of Medicine, Cleveland, OH. 8. Division of Cardiology, University of Colorado School of Medicine, Aurora, CO.
Abstract
After an acute coronary syndrome (ACS), patients with diabetes remain at high risk for additional cardiovascular events despite use of current therapies. Bromodomain and extra-terminal (BET) proteins are epigenetic modulators of inflammation, thrombogenesis, and lipoprotein metabolism implicated in atherothrombosis. The BETonMACE trial tests the hypothesis that treatment with apabetalone, a selective BET protein inhibitor, will improve cardiovascular outcomes in patients with diabetes after an ACS. DESIGN:Patients (n = 2425) with ACS in the preceding 7 to 90 days, with type 2 diabetes and low HDL cholesterol (≤40 mg/dl for men, ≤45 mg/dl for women), receiving intensive or maximum-tolerated therapy with atorvastatin or rosuvastatin, were assigned in double-blind fashion to receive apabetalone 100 mg orally twice daily or matching placebo. Baseline characteristics include female sex (25%), myocardial infarction as index ACS event (74%), coronary revascularization for index ACS (80%), treatment with dual anti-platelet therapy (87%) and renin-angiotensin system inhibitors (91%), median LDL cholesterol 65 mg per deciliter, and median HbA1c 7.3%. The primary efficacy measure is time to first occurrence of cardiovascular death, non-fatal myocardial infarction, or stroke. Assumptions include a primary event rate of 7% per annum in the placebo group and median follow-up of 1.5 years. Patients will be followed until at least 250 primary endpoint events have occurred, providing 80% power to detect a 30% reduction in the primary endpoint with apabetalone. SUMMARY: BETonMACE will determine whether the addition of the selective BET protein inhibitor apabetalone to contemporary standard of care for ACS reduces cardiovascular morbidity and mortality in patients with type 2 diabetes. Results are expected in 2019. Crown
RCT Entities:
After an acute coronary syndrome (ACS), patients with diabetes remain at high risk for additional cardiovascular events despite use of current therapies. Bromodomain and extra-terminal (BET) proteins are epigenetic modulators of inflammation, thrombogenesis, and lipoprotein metabolism implicated in atherothrombosis. The BETonMACE trial tests the hypothesis that treatment with apabetalone, a selective BET protein inhibitor, will improve cardiovascular outcomes in patients with diabetes after an ACS. DESIGN:Patients (n = 2425) with ACS in the preceding 7 to 90 days, with type 2 diabetes and low HDL cholesterol (≤40 mg/dl for men, ≤45 mg/dl for women), receiving intensive or maximum-tolerated therapy with atorvastatin or rosuvastatin, were assigned in double-blind fashion to receive apabetalone 100 mg orally twice daily or matching placebo. Baseline characteristics include female sex (25%), myocardial infarction as index ACS event (74%), coronary revascularization for index ACS (80%), treatment with dual anti-platelet therapy (87%) and renin-angiotensin system inhibitors (91%), median LDL cholesterol 65 mg per deciliter, and median HbA1c 7.3%. The primary efficacy measure is time to first occurrence of cardiovascular death, non-fatal myocardial infarction, or stroke. Assumptions include a primary event rate of 7% per annum in the placebo group and median follow-up of 1.5 years. Patients will be followed until at least 250 primary endpoint events have occurred, providing 80% power to detect a 30% reduction in the primary endpoint with apabetalone. SUMMARY:BETonMACE will determine whether the addition of the selective BET protein inhibitor apabetalone to contemporary standard of care for ACS reduces cardiovascular morbidity and mortality in patients with type 2 diabetes. Results are expected in 2019. Crown
Authors: Kausik K Ray; Stephen J Nicholls; Kevin A Buhr; Henry N Ginsberg; Jan O Johansson; Kamyar Kalantar-Zadeh; Ewelina Kulikowski; Peter P Toth; Norman Wong; Michael Sweeney; Gregory G Schwartz Journal: JAMA Date: 2020-04-28 Impact factor: 56.272
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