Details

Autor(en) / Beteiligte

• Iannuzzo, Gabriella
• Buonaiuto, Alessio
• Calcaterra, Ilenia
• Gentile, Marco
• Forte, Francesco
• Tripaldella, Maria
• Di Taranto, Maria D.
• Giacobbe, Carola
• Fortunato, Giuliana
• Rubba, Paolo O.
• Di Minno, Matteo N. Dario

Titel

Association between causative mutations and response to PCSK9 inhibitor therapy in subjects with familial hypercholesterolemia: A single center real-world study

Ist Teil von

• Nutrition, metabolism, and cardiovascular diseases, 2022-03, Vol.32 (3), p.684-691

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2022

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Familial hypercholesterolemia (FH) is an autosomal dominant disease that leads to cardiovascular (CV) disease. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-I) demonstrated efficacy in low-density lipoprotein cholesterol (LDL-C) reduction and in prevention of CV events. The aim of our study is to evaluate the relationship between LDL receptor (LDLR) mutations and response to PCSK9-I therapy. We evaluated total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) in consecutive patients with FH before PCSK9-I treatment and after 12 (T12w) and 36 (T36w) weeks of treatment. We evaluated LDL-C target achievement according to different mutations in LDLR. Eighty FH subjects (mean age:54 ± 13.3 years), 39 heterozygous (He) with defective LDLR gene mutations, 30 He with null mutations and 11 compound-He or homozygous (Ho) were recruited. At baseline, 69 subjects were under maximal lipid lowering therapy (MLLT) and 11 subjects had statin-intolerance. From baseline to T36w we observed an overall 51% reduction in LDL-C. We found no difference in LDL-C changes between subjects with He-defective mutation and He-null mutations both at T12w (p = 1.00) and T36w (p = 0.538). At T36w, LDL-C target was achieved in 59% of He-defective mutations subjects and in 36% of He-null mutations subgroup (p = 0.069), whereas none of compound-He/Ho-FH achieved LDL-C target. After 36 weeks there were no differences in response to PCSK9-I therapy between different groups of He-FH subjects. Response to PCSK9-I was significantly lower in carriers of compound-He/Ho mutations. Registration number for clinical trials: NCT04313270 extension. •After 36 weeks there were no differences in response to PCSK9-I therapy between FH subgroups according to genotype.•Response to PCSK9-I was significantly lower in carriers of compound-He/Ho mutations.•Target achievement rate still represents an issue in FH patients despite high efficacy of available lipid lowering therapy.