varespladib methyl + atorvastatin

This drug is a **fixed-dose combination** of two small-molecule agents: varespladib methyl and atorvastatin. **Varespladib methyl** is an orally bioavailable prodrug rapidly converted in vivo to varespladib, which acts as a potent, selective inhibitor of secretory phospholipase A2 (sPLA2), targeting particularly the IIA, V, and X isoforms. By blocking sPLA2, varespladib methyl reduces inflammation, modulates lipid metabolism, and may have secondary antithrombotic effects. **Atorvastatin** is a well-established HMG-CoA reductase inhibitor (statin), decreasing cholesterol biosynthesis in the liver and leading to reduced LDL-cholesterol and total cholesterol. This combination was investigated primarily for **acute coronary syndrome** (ACS), aiming to address cardiovascular events by targeting both cholesterol biosynthesis and the inflammatory cascade. Large clinical trials (including VISTA-16) evaluated its effect on cardiovascular biomarkers and events, demonstrating significant reduction in LDL-C and inflammatory markers compared to atorvastatin monotherapy, but no improvement in clinical cardiovascular outcomes. Development for ACS has been discontinued[1][3][5][7].