Nicholls SJ, et al. - Researchers performed a pooled analysis of clinical studies in order to gauge the impact of apabetalone on cardiovascular event rates in patients with established coronary artery disease. Evidence from pooled analysis of short-term studies revealed that treatment with apabetalone vs. placebo was associated with fewer cardiovascular events. Bromodomain and extra-terminal (BET) protein inhibition warrants further investigation as a novel approach to cardiovascular risk reduction.

Methods

• A pooled analysis was performed of patients (n = 798) with coronary artery disease who participated in clinical trials (ASSERT, ASSURE, SUSTAIN) that assessed the effect of 3–6 months of treatment with apabetalone on lipid parameters and coronary atherosclerosis.
• Researchers assessed the incidence of major adverse cardiovascular events (death, myocardial infarction, coronary revascularization, hospitalization for cardiovascular causes) in the treatment groups.

Results

• Findings demonstrated that at baseline, patients treated with apabetalone were more likely to be Caucasian, have a history of dyslipidemia, and be undertreated with ß-blocker and anti-platelet agents.
• Researchers observed that apabetalone vs. placebo produced the following dose-dependent changes: increases in apolipoprotein A-I (apoA-I) of up to 6.7% (P < 0.001), increases in high-density lipoprotein cholesterol (HDL-C) of up to 6.5% (P < 0.001), increases in large HDL particles of up to 23.3% (P < 0.001), and decreases in high-sensitivity C-reactive protein (hsCRP) of - 21.1% (P = 0.04).
• They also noted that apabetalone vs. placebo did not exert impact on atherogenic lipoproteins.
• Additionally, the reported major adverse cardiovascular events were fewer among patients treated with apabetalone versus those treated with placebo (5.9 vs. 10.4%; P = 0.02), a finding that was more prominent in patients with diabetes (5.4 vs. 12.7%; P = 0.02), with baseline HDL-C < 39 mg/dl (5.5 vs. 12.8%; P = 0.01), or with elevated hsCRP levels (5.4 vs. 14.2%; P = 0.02).