Many adults receiving statin therapy remain above recommended low-density lipoprotein cholesterol (LDL-C) targets and require additional lipid-lowering treatment. A phase 3 randomized, double-blind trial published in the Journal of the American College of Cardiology compared the efficacy and safety of enlicitide with currently available oral nonstatin therapies in statin-treated adults at elevated cardiovascular risk. 

The study enrolled 301 adults aged 18 years or older with prior major atherosclerotic cardiovascular disease (ASCVD) or increased risk for a first ASCVD event despite statin therapy. Participants were randomized to receive enlicitide 20 mg daily (n = 101), bempedoic acid 180 mg daily (n = 50), ezetimibe 10 mg daily (n = 50), or combined bempedoic acid plus ezetimibe therapy (n = 100) for 56 days.

Findings

• Mean LDL-C reduction at day 56 was −64.6% (95% CI −68.3% to −60.9%) with enlicitide.
• Comparator LDL-C reductions were −6.3% (95% CI −13.5% to 0.8%) with bempedoic acid, −27.8% (95% CI −32.3% to −23.4%) with ezetimibe, and −36.5% (95% CI −40.8% to −32.2%) with combined bempedoic acid plus ezetimibe.
• Enlicitide demonstrated superior LDL-C lowering compared with each comparator regimen (all P < 0.001).
• Greater reductions in apolipoprotein B (ApoB) and non–high-density lipoprotein cholesterol (non-HDL-C) were also observed with enlicitide compared with all comparator therapies (all P < 0.001).
• Adverse event rates and discontinuations due to adverse events were similar across treatment groups.
   

The findings suggest that enlicitide achieved larger reductions in LDL-C and other atherogenic lipid markers than currently available oral nonstatin therapies in statin-treated adults at elevated cardiovascular risk.