Alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, was found to be both safe and effective in reducing low-density lipoprotein cholesterol (LDL-C) in patients with heterozygous familial hypercholesterolemia (HeFH) across different age groups, according to a post-hoc analysis.
In order to determine whether the safety and efficacy of alirocumab varied depending on a patient’s age, data from four placebo-controlled phase 3 trials (ODYSSEY FH I, FH II, LONG TERM, and HIGH FH) was pooled and analyzed. “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),” the authors explained. They added, “Efficacy endpoints included the percentage change in LDL-C from baseline to week 12 and week 24 for each pool stratified by age.”
For patients enrolled in the FH I and II trials, alirocumab 75mg was administered subcutaneously every 2 weeks (Q2W) and increased at week 12 to 150mg Q2W if the patient’s LDL-C was ≥ 70mg/dL at week 8. For patients enrolled in the HIGH FH and LONG TERM trials, alirocumab 150mg was administered Q2W. The length of each trial was 78 weeks.
“For all age groups, patients in the ITT population receiving alirocumab showed significant reductions in LDL-C compared with placebo from baseline to week 12 and week 24,” the study authors reported. At week 12, mean reductions in LDL-C from baseline (least squares [LS] mean difference vs placebo) were reported as 45.9-52.5% for the alirocumab 75/150mg Q2W group and 49.5-65.6% for the alirocumab 150mg Q2W group. The authors noted that 41.8% of patients in the alirocumab 75mg Q2W blindly received a dose increase at week 12. Mean LDL-C reductions from baseline at week 24 were reported as 50.6-61.0% for the alirocumab 75/150mg Q2W group and 49.5-65.6% for the alirocumab 150mg Q2W group. All interaction p-values were non-significant.
The study authors also reported that the rates of treatment-related adverse events were relatively similar for the alirocumab and placebo groups. It was noted that patients receiving alirocumab did experience more injection site reactions, however, the frequency of these reactions was found to decrease with age (experienced by 8.1% of patients ≥65 years old vs 14.4% of patients 18 to <45 years old).
“Age did not significantly modify LDL-C response to alirocumab, or other lipid parameters, and alirocumab was generally well tolerated in patients with HeFH across all age groups studied, including older patients,” the authors concluded.
Ginsberg HN, Tuomilehto J, Hovingh GK, Cariou B, Santos RD, Brown AS. Impact of age on the efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia. Cardiovascular Drugs and Therapy. 2019. doi.org/10.1007/s10557-019-06852-6.