lapaquistat acetate + rosuvastatin

Lapaquistat acetate + rosuvastatin is a discontinued investigational combination therapy for hypercholesterolemia and dyslipidemia. Lapaquistat acetate is a small molecule squalene synthase inhibitor that blocks cholesterol biosynthesis at the squalene synthase step, reducing low-density lipoprotein (LDL) cholesterol and other cardiovascular risk markers. Rosuvastatin is an HMG-CoA reductase inhibitor (statin) that lowers LDL cholesterol by inhibiting the early rate-limiting step in cholesterol synthesis, leading to upregulation of hepatic LDL receptors and increased clearance of serum cholesterol. The combination was studied to provide additive or synergistic lipid-lowering effects; however, development was terminated due to hepatic safety concerns associated with lapaquistat acetate[1][2][4][7].