Association between causative mutations and response to PCSK9 inhibitor therapy in subjects with familial hypercholesterolemia: A single center real-world study
| Autor: | Alessio Buonaiuto, Maria Donata Di Taranto, Ilenia Calcaterra, Marco Gentile, Paolo Rubba, Giuliana Fortunato, Carola Giacobbe, M. Tripaldella, Matteo Nicola Dario Di Minno, Gabriella Iannuzzo, Francesco Forte |
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| Přispěvatelé: | Iannuzzo, G., Buonaiuto, A., Calcaterra, I., Gentile, M., Forte, F., Tripaldella, M., Di Taranto, M. D., Giacobbe, C., Fortunato, G., Rubba, P. O., Di Minno, M. N. D. |
| Rok vydání: | 2022 |
| Předmět: |
Adult
medicine.medical_specialty Endocrinology Diabetes and Metabolism Familial hypercholesterolemia Medicine (miscellaneous) medicine.disease_cause Single Center Gastroenterology Hyperlipoproteinemia Type II Proprotein convertase subtilisin/kexin type 9 inhibitors Internal medicine Humans Medicine Low-density lipoprotein cholesterol Aged Mutation Nutrition and Dietetics business.industry PCSK9 PCSK9 Inhibitors Autosomal dominant trait Middle Aged Proprotein convertase medicine.disease Receptors LDL Low-density lipoprotein receptor gene LDL receptor Kexin lipids (amino acids peptides and proteins) Proprotein Convertase 9 Cardiology and Cardiovascular Medicine business |
| Zdroj: | Nutrition, Metabolism and Cardiovascular Diseases. 32:684-691 |
| ISSN: | 0939-4753 |
| DOI: | 10.1016/j.numecd.2021.10.025 |
| Popis: | Background and Aims 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. Methods and Results 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 homozygotes (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. Conclusions 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. |
| Databáze: | OpenAIRE |
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