Abstract 16967: Treatment Effect of Alirocumab in Patients With Heterozygous Familial Hypercholesterolemia With Baseline Low-density Lipoprotein Cholesterol Levels >130 mg/dL Receiving High Intensity Statin
Introduction: Patients with heterozygous familial hypercholesterolemia (HeFH) and LDL-C levels far from guideline-recommended goals despite treatment with high intensity statin ± other lipid-lowering therapies are at very high cardiovascular risk, and require additional intensive LDL-C lowering treatment. This analysis evaluated the efficacy and safety of alirocumab (ALI) in patients with HeFH and LDL-C levels >130 mg/dL, despite high-intensity statin therapy.
Methods: ALI was assessed as add-on therapy for 610 HeFH patients with baseline LDL-C >130 mg/dL receiving high intensity statin in 4 randomized, 18-month, placebo (PBO)-controlled, Phase 3 ODYSSEY trials (FH I, FH II, HIGH FH, LONG TERM [LTS]). Data were pooled based on initial ALI dose. In FH I/II, patients received PBO [N=109] or ALI 75 mg Q2W [N=216], which was increased to 150 mg Q2W at week (W)12 if LDL-C was ≥70 mg/dL at W8 (58.2% of patients). In HIGH FH/LTS, patients received PBO [N=90] or ALI 150 mg Q2W [N=195]. Endpoints were absolute and % change in calculated LDL-C from baseline to W12 and W24.
Results: Baseline characteristics were comparable between groups (Table). In both pools, patients on ALI had significant LDL-C reductions from baseline to W12 and W24 (Table). The majority of very high or high CV risk patients with baseline LDL-C >130 mg/dL reached EAS/ESC-recommended goals of calculated LDL-C <70 or <100 mg/dL with ALI: 68.4% ALI vs 0% PBO in FH I/II, and 59.2% ALI vs 2.3% PBO in HIGH FH/LTS at W24 (all P<0.0001 vs PBO; Table). TEAE rates were comparable between groups (77.1% ALI vs 78.9% PBO; P>0.05). The most commonly reported TEAEs in ALI-treated patients included nasopharyngitis, influenza and injection site reactions (Table).
Conclusions: These data show a consistent benefit of alirocumab as additional therapy to high intensity statin in HeFH patients with baseline LDL-C values of >130 mg/dL, allowing many to achieve LDL-C levels previously considered unobtainable in this patient population.
Author Disclosures: J.J. Kastelein: Consultant/Advisory Board; Modest; Sanofi, Amgen, Pfizer, Eli Lilly, The Medicines Company, Regeneron. M. Krempf: Speakers Bureau; Modest; Sanofi, Amgen, MSD. Honoraria; Modest; Sanofi, Amgen, MSD. F. Raal: Research Grant; Modest; Amgen, Sanofi for conducting clinical trials with PCSK9-inhibitors. Speakers Bureau; Modest; Amgen, Sanofi, Pfizer, AstraZeneca. Honoraria; Modest; Amgen, Sanofi, Pfizer, AstraZeneca. Consultant/Advisory Board; Modest; Amgen, Sanofi. V. Valcheva: Employment; Significant; Sanofi. S. Guillonneau: Employment; Significant; Sanofi. S.R. Iorga: Employment; Significant; Regeneron Pharmaceuticals, Inc. E. Bruckert: Research Grant; Modest; Amgen, Danone, Aegerion. Honoraria; Modest; Genfit, AstraZeneca. Consultant/Advisory Board; Modest; Aegerion, Amgen, MSD, Unilever, Danone, Sanofi, Regeneron Pharmaceuticals, Inc, Ionis, Chiesi, Eli Lilly, Rottapharm-MEDA.
- © 2016 by American Heart Association, Inc.