Does Genotype Affect the Efficacy of PCSK9 Inhibitors in the Treatment of Familial Hypercholesterolemia?

Abstract

This review discusses whether patients' genotype affects the efficacy of PCSK9 inhibitors in treating familial hypercholesterolemia and how this might influence clinical management. Currently, available evidence consistently demonstrates and is in good agreement that, in general, the LDL-C-lowering effect of PCSK9 inhibitors is similar across genotypes, except for compound heterozygous and homozygous familial hypercholesterolemia (FH). However, it remains to be seen whether the comparable therapeutic effect in lowering LDL-C level also leads to a comparable degree of cardiovascular risk reduction with different genotypes. Generally, the level of LDL-C reduction following PCSK9 inhibitor treatment is similar within different genotypes. Hence, genotype is a less reliable predictor for further LDL-C level reduction on PCSK9 inhibitor therapy, and attention should be given to other external influences, especially for heterozygous FH.