Impact of Age on the Efficacy and Safety of Alirocumab in Patients with Heterozygous Familial Hypercholesterolemia

PurposeThis post-hoc analysis examined whether age modified the efficacy and safety of alirocumab, a PCSK9 inhibitor, in patients with heterozygous familial hypercholesterolemia (HeFH), using pooled data from four 78-week placebo-controlled phase 3 trials (ODYSSEY FH I, FH II, LONG TERM, and HIGH FH).MethodsData from 1257 patients with HeFH on maximally tolerated statin other lipid-lowering therapies were analyzed by an alirocumab dose regimen and by age subgroups (18 to <45, 45 to <55, 55 to <65, and 65years). In the FH I and II trials, patients received 75mg subcutaneously every 2weeks (Q2W), with dose increase to 150mg Q2W at week 12 if week 8 low-density lipoprotein cholesterol (LDL-C) was 70mg/dl. In HIGH FH and LONG TERM, patients received 150mg alirocumab Q2W.ResultsBaseline characteristics were similar between treatment groups across all age groups; the proportion of males decreased whereas the proportion of patients with coronary heart disease, diabetes, hypertension, and declining renal function increased with increasing age. Mean LDL-C reductions at week 24 were consistent across age groups (50.6-61.0% and 51.1-65.8% vs. placebo for the 75/150 and 150mg alirocumab dose regimens, respectively; both non-significant interaction P-values). Treatment-emergent adverse events occurred in similar frequency in alirocumab- and placebo-treated patients regardless of age, except for injection-site reactions, which were more common in alirocumab than placebo but declined in frequency with age.Conclusions Alirocumab treatment resulted in significant LDL-C reductions at weeks 12 and 24 and was generally well tolerated in patients with HeFH across all age groups studied.