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

Ginsberg HN1, Tuomilehto J2,3, Hovingh GK4, Cariou B5, Santos RD6,7, Brown AS8, Sanganalmath SK9, Koren A10, Thompson D9, Raal FJ11.

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Abstract

PURPOSE:

This 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).

METHODS:

Data 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 ≥ 65 years). In the FH I and II trials, patients received 75 mg subcutaneously every 2 weeks (Q2W), with dose increase to 150 mg Q2W at week 12 if week 8 low-density lipoprotein cholesterol (LDL-C) was ≥ 70 mg/dl. In HIGH FH and LONG TERM, patients received 150 mg alirocumab Q2W.

RESULTS:

Baseline 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 150 mg 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.