In patients with recent acute coronary syndrome, does apabetalone (a selective inhibitor of bromodomain and extraterminal proteins) reduce the risk of major adverse cardiovascular events when added to standard care?
In this randomized clinical trial that included 2425 patients with acute coronary syndrome, type 2 diabetes, and low high-density lipoprotein cholesterol levels, treatment with apabetalone compared with placebo and added to standard therapy did not significantly reduce the risk of cardiovascular death, nonfatal myocardial infarction, or stroke (10.3% vs 12.4%, respectively; hazard ratio, 0.82).
Apabetalone did not significantly reduce major adverse cardiovascular events after acute coronary syndrome.
Bromodomain and extraterminal proteins are epigenetic regulators of gene transcription. Apabetalone is a selective bromodomain and extraterminal protein inhibitor targeting bromodomain 2 and is hypothesized to have potentially favorable effects on pathways related to atherothrombosis. Pooled phase 2 data suggest favorable effects on clinical outcomes.
To test whether apabetalone significantly reduces major adverse cardiovascular events.
Design, Setting, and Participants
A randomized, double-blind, placebo-controlled trial, conducted at 190 sites in 13 countries. Patients with an acute coronary syndrome in the preceding 7 to 90 days, type 2 diabetes, and low high-density lipoprotein cholesterol levels were eligible for enrollment, which started November 11, 2015, and ended July 4, 2018, with end of follow-up on July 3, 2019.
Patients were randomized (1:1) to receive apabetalone, 100 mg orally twice daily (n = 1215), or matching placebo (n = 1210) in addition to standard care.
Main Outcomes and Measures
The primary outcome was a composite of time to the first occurrence of cardiovascular death, nonfatal myocardial infarction, or stroke.
Among 2425 patients who were randomized (mean age, 62 years; 618 women [25.6%]), 2320 (95.7%) had full ascertainment of the primary outcome. During a median follow-up of 26.5 months, 274 primary end points occurred: 125 (10.3%) in apabetalone-treated patients and 149 (12.4%) in placebo-treated patients (hazard ratio, 0.82 [95% CI, 0.65-1.04]; P = .11). More patients allocated to apabetalone than placebo discontinued study drug (114 [9.4%] vs 69 [5.7%]) for reasons including elevations of liver enzyme levels (35 [2.9%] vs 11 [0.9%]).
Conclusions and Relevance
Among patients with recent acute coronary syndrome, type 2 diabetes, and low high-density lipoprotein cholesterol levels, the selective bromodomain and extraterminal protein inhibitor apabetalone added to standard therapy did not significantly reduce the risk of major adverse cardiovascular events.
ClinicalTrials.gov Identifier: NCT02586155
Ray KK, Nicholls SJ, Buhr KA, et al. Effect of Apabetalone Added to Standard Therapy on Major Adverse Cardiovascular Events in Patients With Recent Acute Coronary Syndrome and Type 2 Diabetes: A Randomized Clinical Trial. JAMA. 2020;323(16):1565–1573. doi:10.1001/jama.2020.3308
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