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

Cardiovasc Drugs Ther. 2019 Feb;33(1):69-76. doi: 10.1007/s10557-019-06852-6.

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.

Keywords: Cardiovascular disease prevention; Cholesterol-lowering drugs; Clinical trials; LDL-C; PCSK9.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Anticholesteremic Agents / adverse effects
  • Anticholesteremic Agents / therapeutic use*
  • Biomarkers / blood
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol, LDL / blood*
  • Clinical Trials, Phase III as Topic
  • Down-Regulation
  • Female
  • Genetic Predisposition to Disease
  • Heterozygote*
  • Humans
  • Hyperlipoproteinemia Type II / complications
  • Hyperlipoproteinemia Type II / diagnosis
  • Hyperlipoproteinemia Type II / drug therapy*
  • Hyperlipoproteinemia Type II / genetics
  • Male
  • Middle Aged
  • Phenotype
  • Proprotein Convertase 9 / antagonists & inhibitors*
  • Proprotein Convertase 9 / metabolism
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Anticholesteremic Agents
  • Biomarkers
  • Cholesterol, LDL
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • alirocumab