Nuove terapie ipolipemizzanti per i pazienti con ipercolesterolemia familiare Position Paper della Società Italiana per lo studio della Arteriosclerosi

Familial hypercholesterolaemia (FH) is the main genetic cause of premature coronary heart disease (CHD), characterized by raised serum LDL-cholesterol levels, which result in excess deposition of cholesterol in tissues. FH results from defects in the hepatic uptake and degradation of LDL via the LDL-receptor pathway. Owing to severe underdiagnosis and undertreatment of FH, there is an urgent worldwide need for diagnostic screening together with early and aggressive treatment. This position paper aims to improve awareness of the need for early detection and management of FH patients, to determine treatment objectives, and to delineate treatment priorities.FH is diagnosed either on phenotypic criteria and/or positive genetic testing. We recommend cascade screening of families using a combined phenotypic and genotypic strategy. A healthy lifestyle and early maximal statin treatment are the cornerstones of management of FH. In heterozygous FH patients, LDLcholesterol targets are <2.5 mmol/L (<100 mg/dL) and <1.8 mmol/L (<70 mg/dL) for adults with known CHD, other major risk factors, or documented preclinical atherosclerosis. In addition to lifestyle and dietary counselling, treatment priorities are maximal potent statin dose, ezetimibe, and bile acid binding resins. PCSK9 inhibitors and lipoprotein apheresis can be offered in treatment-resistant or intolerant patients. In homozygous FH patients, LDL-cholesterol targets are <1.8 mmol/L (<70 mg/dL) or at least 50% reduction. Lifestyle intervention and maximal statin therapy are the mainstays of treatment. Even at the highest doses of the most efficacious statins, however, only modest reductions in LDL-C plasma levels are observed in most patients. Adjunctive lipoprotein apheresis is recommended where available, together with new therapeutic approaches recently approved: lomitapide and mipomersen (the latter not in Italy). In FH patients, we recommend regular follow-up, including liver function tests, steatosis, vascular status.