Una historia resumida. La inhibición de la PCSK9 y su desarrollo clínico

Hypercholesterolaemia is one of the major cardiovascular risk factors; however, conventional treatment with diet, exercise and cholesterol-lowering drugs are insufficient to control low-density lipoprotein (LDL) cholesterol in a significant number of patients. Inhibition of the PCSK9 protein by using specific monoclonal antibodies increases the number of LDL cholesterol receptors in the hepatocyte, contributing to LDL destruction. The use of these drugs, whether as monotherapy or in combination with statins and ezetimibe, significantly reduces LDL cholesterol, allowing LDL cholesterol levels in most patients to be maintained within limits recommended by clinical practice guidelines. To determine their clinical efficacy, 3 multicenter trials of morbidity and mortality have been conducted with alirocumab, evolocumab and bococizumab. The trial involving evolocumab, a fully human monoclonal antibody, demonstrated a significant reduction of the primary efficacy endpoint, including cardiovascular mortality, myocardial infarction, stroke, unstable angina or myocardial revascularisation. However, no clinical benefit was observed with bococizumab (a humanised but not fully human monoclonal antibody), probably due to a decrease in efficacy secondary to the formation of anti-drug antibodies. This new therapeutic option is already used in clinical practice and is considered a new advance in the prevention of cardiovascular disease.