PCSK9i: proprotein convertase subtilisin/kexin type 9 inhibitor a new phase of lipid-lowering treatment

Abstract

One of the largest global causes of morbidity and mortality is cardiovascular disease (CVD). Elevated low-density lipoprotein (LDL) levels and adverse cardiovascular outcomes are linked to increased levels of the proprotein convertase subtilisin/kexin type 9 (PCSK9) in the blood. Inhibiting PCSK9 lowers the levels of circulating LDL-C by increasing the extracellular membrane density of LDL receptors. Regulators have approved the use of PCSK9 antibodies to treat patients with high LDL-cholesterol (LDL-C) levels. It can reduce LDL-C in patients receiving statin therapy by as much as 60% with clinical advantages, such as lower incidence of myocardial infarction or stroke. The outcomes of the major clinical trials, ODYSSEY and the FOURIER indicated a statistically significant decrease in mortality with a relative risk reduction of 15% in both trials. Two monoclonal antibodies (evolocumab and alirocumab) are PCSK9 inhibitors approved by the FDA for the treatment of familial hypercholesterolaemia, and patients who require additional therapies along with healthy diet and statin medication.