Correlation Between Different Ldl-R Mutations And Response To Ab-Pcsk9 Therapy In A Group Of Patient With Genetic Diagnosis Of Familial Hypercholesterolemia. Preliminary Report
EUROPEAN HEART JOURNAL(2020)
Abstract
Abstract Introduction Familial hypercholesterolemia (FH) is an autosomal dominant disease that leads to premature cardiovascular disease (CAD). The availability of ab-PCSK9 has changed the approach to therapy. Purpose To evaluate the relationship between different types of mutations in LDLR gene and response to ab-PCSK9. Methods 73 FH patients, 33 women and 40 men (53.9±13. yrs), in primary prevention (N=46) and secondary prevention (N=27), were recruited. This sample included patients with mutations in LDLR gene: heterozygotes for missense mutations (N=31), for null mutations (N=31), compound heterozygotes or homozygotes (N=11). At baseline, the whole sample had a maximally tolerated lipid lowering therapy (MT-LLT) without ab-PCSK9; 16 patients had MT-LLTs intolerance. After 160 days with ab-PCSK9 therapy we evaluated the achievement of a goal (LDL-C<70 mg/dL in primary prevention without Diabetes Mellitus, LDL-C<55 mg/dL). Results After 160 days of therapy with ab-PCSK9 (45 patients on Alirocumab, 28 patients on Evolocumab) and MT-LLT, 29/73 patients (39.7%) of the whole sample achieve the goal of LDL-C. Of them 14/29 (48.2%) were in primary prevention, 15/29 (51.7%) in secondary prevention, no difference in achievement of the goal. We then evaluated the percent of patients achieving the goal of LDL-C: 15/31 (48.3%) patients with missense mutation and 14/31 (45.1%) patients with null mutation, no significant difference among groups; 0/11 compound heterozygotes or homozygotes; 3/16 (18.7%) MT-LLTs intolerance. The other main cardiovascular risk factors did not influence of the achievement the goal of LDL cholesterol. Conclusions Lack of correlation between type of mutation in heterozygous FH patients and ab-PCSK9 therapy response; response was significantly poorest in patients with compound heterozygosis or homozygosis mutation as compared to heterozygotes; the intolerance to MT-LLT was significant in the achievement of the goal of LDL-C. Different between guideline 2016 vs 2019 Funding Acknowledgement Type of funding source: None
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Key words
familial hypercholesterolemia,genetic diagnosis,mutations,ab-pcsk
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