Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: Results of a 24 week,double-blind,randomized Phase 3 trial |
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Authors: | Eli M Roth Marja-Riitta Taskinen Henry N Ginsberg John JP Kastelein Helen M Colhoun Jennifer G Robinson Laurence Merlet Robert Pordy Marie T Baccara-Dinet |
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Institution: | 1. The Sterling Research Group, Cincinnati, OH, USA;2. Cardiovascular Research Unit, Diabetes and Obesity Research Program, University of Helsinki, Finland;3. Columbia University, New York, NY, USA;4. Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands;5. Medical Research Institute, University of Dundee, Dundee, UK;6. College of Public Health, University of Iowa, IA, USA;g Sanofi, Paris, France;h Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA;i Sanofi, Montpellier, France |
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Abstract: | BackgroundEfficacy and safety of alirocumab were compared with ezetimibe in hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy.MethodsIn 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.ResultsMean (SD) baseline LDL-C levels were 141.1 (27.1) mg/dL (alirocumab) and 138.3 (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).ConclusionsAlirocumab 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. |
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Keywords: | AE adverse event Apo apolipoprotein BMI body mass index CV cardiovascular CVD cardiovascular disease EOT end of treatment EZE ezetimibe HbA1c glycated hemoglobin A1c HDL-C high-density lipoprotein cholesterol IQR interquartile range ITT intent-to-treat LDL-C low-density lipoprotein cholesterol LDLR low-density lipoprotein receptors LLN lower limit of normal Lp(a) lipoprotein (a) LS least squares mITT modified intent-to-treat NCEP-ATPIII National Cholesterol Education Program Adult Treatment Panel III NEC not elsewhere classified Non-HDL-C non-high-density lipoprotein cholesterol PCSK9 proprotein convertase subtilisin/kexin 9 Q2W every 2 weeks R randomization SAEs serious adverse events SC subcutaneously SCORE systematic coronary risk estimation SD standard deviation SE standard error TEAEs treatment-emergent adverse events TGs triglycerides ULN upper limit of normal |
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