Effect of BET Protein Inhibition With Apabetalone on Cardiovascular Outcomes in Patients With Acute Coronary Syndrome and Diabetes - BETonMACE
Contribution To Literature:
The BETonMACE trial showed that apabetalone is not superior to placebo on a background of optimal medical therapy in reducing adverse cardiovascular outcomes among patients with type 2 diabetes mellitus and recent acute coronary syndrome.
The goal of the trial was to assess the safety and efficacy of apabetalone, a drug that results in BET protein inhibition, among patients with diabetes mellitus and acute coronary syndrome.
During the run-in phase, patients received either 40-80 mg of atorvastatin or 20-40 mg of rosuvastatin for 1-2 weeks. Following this, eligible patients were randomized in a 1:1 fashion to either apabetalone 100 mg BID (n = 1,212) or placebo (n = 1,206).
- Total screened: 3,937
- Total number of enrollees: 2,425
- Duration of follow-up: 26 months
- Mean patient age: 62 years
- Percentage female: 26%
- Type 2 diabetes mellitus
- Acute coronary syndrome 7-90 days prior
- Low high-density lipoprotein cholesterol (HDL-C) (<40 mg/dl for males, <45 mg/dl for females)
- Planned further coronary revascularization
- Previous or current diagnosis of heart failure
- Coronary artery bypass grafting within 90 days
- Estimated glomerular filtration rate <30 or need for dialysis
Other salient features/characteristics:
- Duration of diabetes mellitus: 8.4 years
- ST-segment elevation myocardial infarction (STEMI): 38%
- Hemoglobin A1c: 7.4%; baseline low-density lipoprotein cholesterol (LDL-C): 70%
- Percutaneous coronary intervention for acute coronary syndrome: 79%
- High-intensity statin: 90%; dual antiplatelet therapy: 88%
- SGLT-2 inhibitor: 12.4%
The primary outcome, cardiovascular death, MI, or stroke for apabetalone vs. placebo, was 10.3% vs. 12.4% (p = 0.11).
- Cardiovascular death (excluding death from undetermined cause)/MI/stroke: 9.3% vs. 11.6% (p = 0.06)
Secondary outcomes for apabetalone vs. placebo:
- Cardiovascular death/MI: 9.2% vs.11.5% (p > 0.05)
- Stroke: 1.4% vs. 1.4% (p > 0.05)
- All-cause mortality: 5.0% vs. 5.7% (p > 0.05)
- Change in HDL-C from baseline at 100 weeks: 16.2% vs. 10.4% (p = 0.001)
- Change in LDL-C from baseline at 100 weeks: 11.5% vs. 14.9% (p = 0.35)
The results of this trial indicate that apabetalone, a drug that results in BET protein inhibition, is not superior to placebo on a background of optimal medical therapy in reducing adverse cardiovascular outcomes among patients with type 2 diabetes mellitus and recent acute coronary syndrome. It appears that the trial was a bit underpowered to show a benefit due to lower than expected event rates. Salutary effects on metabolic parameters, particularly HDL-C, were observed. The incidence of transaminitis was higher with this drug.
Presented by Kausik K. Ray at the American Heart Association Annual Scientific Sessions (AHA 2019), Philadelphia, PA, November 16, 2019.
Clinical Topics: Acute Coronary Syndromes, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Prevention, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and ACS
Keywords: AHA19, AHA Annual Scientific Sessions, Acute Coronary Syndrome, Cholesterol, HDL, Cholesterol, LDL, Diabetes Mellitus, Type 2, Dyslipidemias, Hemoglobin A, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Metabolic Syndrome X, Myocardial Infarction, Percutaneous Coronary Intervention, Primary Prevention, Stroke
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