Efficacy of lipid-­lowering therapy in patients with genetically confirmed familial hypercholesterolemia

Aim. To evaluate the effectiveness of lipid-lowering therapy (LLT) in patients with genetically confirmed familial hypercholesterolemia (FH).

Material and methods. The study included 140 patients with genetically confirmed FH, followed at the Lipid Center of the National Medical Research Center for Therapy and Preventive Medicine. Participants ranged in age from 19 to 80 years. Lipid profile parameters, clinical and genetic data were analyzed.

Results. In 89% of the patients studied, a variant in the LDLR gene was identified as the cause of FH, while in 11%, a variant in the APOB gene was identified. No variants in the PCSK9 gene were detected. High penetrance of the identified FH variants was demonstrated. In patients with a LDLR gene, low-density lipoprotein cholesterol (LDL-C) levels without LLT (median [interquartile range] 8,49 [7,43; 9,31] mmol/L) were higher than in patients with a variant in the APOB gene (7,55 [6,22; 8,33] mmol/L) (p<0,001). No patient achieved the target LDL-C level with statin monotherapy. The study demonstrated the high efficacy of triple LLT (statin/ezetimibe/PCSK9 inhibitors) as follows: 95,4% of patients with high cardiovascular risk (CVR) achieved the target LDL-C level, while only 63,6% in the very high CVR group.

Conclusion. The study results demonstrate that patient genetic characteristics influence baseline LDL-C levels but do not affect the efficacy of LLT. To achieve the target LDL-C level of 36,4%, patients in the very high CVD group should add bempedoic acid or lipid apheresis to the triple therapy (statin/ezetimibe/PCSK9 inhibitors).

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