[PERSONALIZED APPROACH TO LIPID-LOWERING THERAPY]

Individualized therapeutic strategy of dyslipidemias, classically relies upon a phenotypic approach. The pattern of lipid profile allows the choice of the best pharmacological option (statin, fibrate) and the patient's clinical risk profile allows the definition of therapeutic goals, especially LDL cholesterol target levels. Dyslipidemias have a major genetic component, which is best illustrated by familial hypercholesterolemia, with its two heterozygous and homozygous forms. There is a huge between-subject variability in the response to lipid-lowering therapies (especially to statins) and ongoing pharmacogenetic and pharmacogenomic studies should help to better understand this inter-individual heterogeneity. The recent discovery of mutations in the PCSK9 rene opened new perspectives regarding the understanding of some forms of familial hypercholesterolemia and led to the development of monoclonal antibodies that selectively inhibit PCSK9. These PCSK9 inhibitors allow, when combined to a statin, drastic reductions in LDL cholesterol concentrations, even when familial hypercholesterolemia is present. They are currently tested in large prospective controlled trials aiming to demonstrate a significant reduction in the residual cardiovascular risk in statin-treated patients.