evolocumab + rosuvastatin + atorvastatin + ezetimibe

This is a combination therapy consisting of four lipid-lowering agents: **evolocumab** (a monoclonal antibody and PCSK9 inhibitor), **rosuvastatin** and **atorvastatin** (both HMG-CoA reductase inhibitors or statins), and **ezetimibe** (a cholesterol absorption inhibitor). Each drug acts via a distinct mechanism to lower low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular risk. - **Evolocumab** binds to and inhibits PCSK9, preventing degradation of LDL receptors and enabling increased clearance of LDL-C from plasma[4][8]. - **Rosuvastatin** and **atorvastatin** are statins that inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, resulting in upregulation of hepatic LDL receptors and hence increased LDL-C clearance. - **Ezetimibe** inhibits the absorption of cholesterol at the brush border of the small intestine, leading to decreased cholesterol delivery to the liver and increased hepatic LDL receptor expression[3][5][7]. This combination would achieve highly potent LDL-C lowering, and may be used for patients with severe or refractory hypercholesterolemia, though it is not known to be available as a fixed-dose product. Its efficacy and safety have been studied in various permutations (e.g., evolocumab plus rosuvastatin, or evolocumab plus atorvastatin, or statin plus ezetimibe), but not all four in a single product[1][4][6][8][10].