PCSK9 inhibitors: A new era of lipid lowering therapy

Core Tip

Core tip: Hyperlipidemia is a well-established risk factor for developing cardiovascular disease (CVD). However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia. The Food and Drug Administration has approved two novel medications for low-density lipoprotein (LDL)-cholesterol reduction in this patient population: Evolocumab and Alirocumab. These agents target and inactivate proprotein convertase subtilsin-kexin type 9 (PCSK9), a hepatic protease that attaches and internalizes LDL receptors into lysosomes hence promoting their destruction. By preventing LDL receptor destruction, LDL-C levels can be lowered 50%-60% above that achieved by statin therapy alone. PCSK9 inhibitors are an exciting agent for reducing LDL-C and have ushered in a new era of lipid lowering therapy.