1. Effect of selective BET protein inhibitor apabetalone on cardiovascular outcomes in patients with acute coronary syndrome and diabetes: Rationale, design, and baseline characteristics of the BETonMACE trial
- Author
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Ewelina Kulikowski, Kamyar Kalantar-Zadeh, Kausik K. Ray, Henry D Ginsberg, Norman C.W. Wong, Peter P. Toth, Jan O. Johansson, Stephen J. Nicholls, Michael O. Sweeney, Jeffrey L. Cummings, and Gregory G. Schwartz
- Subjects
Male ,Acute coronary syndrome ,medicine.medical_specialty ,medicine.medical_treatment ,Atorvastatin ,Myocardial Infarction ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Drug Administration Schedule ,1117 Public Health and Health Services ,Renin-Angiotensin System ,03 medical and health sciences ,Percutaneous Coronary Intervention ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,Diabetes mellitus ,medicine ,Clinical endpoint ,Humans ,Rosuvastatin ,030212 general & internal medicine ,Myocardial infarction ,Acute Coronary Syndrome ,Renal Insufficiency, Chronic ,Rosuvastatin Calcium ,1102 Cardiorespiratory Medicine and Haematology ,Aged ,Quinazolinones ,business.industry ,Cholesterol, HDL ,Proteins ,Percutaneous coronary intervention ,Cholesterol, LDL ,medicine.disease ,Stroke ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Cardiovascular System & Hematology ,Female ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,business ,Diabetic Angiopathies ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
Background 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.
- Published
- 2019