TY - JOUR
T1 - Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia
T2 - Results of a 24week, double-blind, randomized Phase 3 trial
AU - Roth, Eli M.
AU - Taskinen, Marja-Riitta
AU - Ginsberg, Henry N.
AU - Kastelein, John J. P.
AU - Colhoun, Helen M.
AU - Robinson, Jennifer G.
AU - Merlet, Laurence
AU - Pordy, Robert
AU - Baccara-Dinet, Marie T.
N1 - Copyright © 2014. Published by Elsevier Ireland Ltd.
PY - 2014/9
Y1 - 2014/9
N2 - Background:Efficacy and safety of alirocumab were compared with ezetimibe in hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy. Methods In a Phase 3, randomized, double-blind, double-dummy study (NCT01644474), patients (low-density lipoprotein cholesterol [LDL-C] 100–190 mg/dL, 10-year risk of fatal cardiovascular events = 1%–<5% [systemic coronary risk estimation]) were randomized to ezetimibe 10 mg/day (n = 51) or alirocumab 75 mg subcutaneously (via 1mL autoinjector) every 2 weeks (Q2W) (n = 52), with dose up-titrated to 150 mg Q2W (also 1 mL) at week 12 if week 8 LDL-C was = 70 mg/dL. Primary endpoint was mean LDL-C % change from baseline to 24 weeks, analyzed using all available data (intent-to-treat approach, ITT). Analyses using on-treatment LDL-C values were also conducted.Results: Mean (SD) baseline LDL-C levels were 141.1 (27.1) mg/dL (alirocumab) and138.3 (24.5) mg/dL (ezetimibe). The 24-week treatment period was completed by 85% of alirocumab and 86% of ezetimibe patients. Least squares mean (SE) LDL-C reductions were 47 (3)% with alirocumab versus 16 (3)% with ezetimibe (ITT; p < 0.0001) and 54 (2)% versus 17 (2)% (on-treatment; p < 0.0001).At week 12, before up-titration, alirocumab 75 mg Q2W reduced LDL-C by 53 (2)% (on-treatment). Injection site reactions were infrequent (< 2% and < 4% of alirocumab and ezetimibe patients,
respectively). Conclusions: Alirocumab demonstrated significantly greater LDL-C lowering versus ezetimibe after 24 weeks with the lower 75 mg Q2W dose sufficient to provide = 50% LDL-C reduction in the majority of the patients. Adverse events were comparable between groups.
AB - Background:Efficacy and safety of alirocumab were compared with ezetimibe in hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy. Methods In a Phase 3, randomized, double-blind, double-dummy study (NCT01644474), patients (low-density lipoprotein cholesterol [LDL-C] 100–190 mg/dL, 10-year risk of fatal cardiovascular events = 1%–<5% [systemic coronary risk estimation]) were randomized to ezetimibe 10 mg/day (n = 51) or alirocumab 75 mg subcutaneously (via 1mL autoinjector) every 2 weeks (Q2W) (n = 52), with dose up-titrated to 150 mg Q2W (also 1 mL) at week 12 if week 8 LDL-C was = 70 mg/dL. Primary endpoint was mean LDL-C % change from baseline to 24 weeks, analyzed using all available data (intent-to-treat approach, ITT). Analyses using on-treatment LDL-C values were also conducted.Results: Mean (SD) baseline LDL-C levels were 141.1 (27.1) mg/dL (alirocumab) and138.3 (24.5) mg/dL (ezetimibe). The 24-week treatment period was completed by 85% of alirocumab and 86% of ezetimibe patients. Least squares mean (SE) LDL-C reductions were 47 (3)% with alirocumab versus 16 (3)% with ezetimibe (ITT; p < 0.0001) and 54 (2)% versus 17 (2)% (on-treatment; p < 0.0001).At week 12, before up-titration, alirocumab 75 mg Q2W reduced LDL-C by 53 (2)% (on-treatment). Injection site reactions were infrequent (< 2% and < 4% of alirocumab and ezetimibe patients,
respectively). Conclusions: Alirocumab demonstrated significantly greater LDL-C lowering versus ezetimibe after 24 weeks with the lower 75 mg Q2W dose sufficient to provide = 50% LDL-C reduction in the majority of the patients. Adverse events were comparable between groups.
KW - PCSK9
KW - Monoclonal antibodies
KW - Cholesterol-lowering drugs
KW - HYPERCHOLESTEROLEMIA
KW - LDL-C
KW - Alirocumab
U2 - 10.1016/j.ijcard.2014.06.049
DO - 10.1016/j.ijcard.2014.06.049
M3 - Article
C2 - 25037695
SN - 0167-5273
VL - 176
SP - 55
EP - 61
JO - International Journal of Cardiology
JF - International Journal of Cardiology
IS - 1
ER -