Eli M Roth1, Marja-Riitta Taskinen2, Henry N Ginsberg3, John J P Kastelein4, Helen M Colhoun5, Jennifer G Robinson6, Laurence Merlet7, Robert Pordy8, Marie T Baccara-Dinet9. 1. The Sterling Research Group, Cincinnati, OH, USA. Electronic address: eroth@sterlingresearch.org. 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. 7. Sanofi, Paris, France. 8. Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA. 9. Sanofi, Montpellier, France.
Abstract
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 10mg/day (n=51) or alirocumab 75 mg subcutaneously (via 1-mL 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) 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). 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.
RCT Entities:
BACKGROUND: Efficacy and safety of alirocumab were compared with ezetimibe in hypercholesterolemicpatients 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 10mg/day (n=51) or alirocumab 75 mg subcutaneously (via 1-mL 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) and 138.3 (24.5) mg/dL (ezetimibe). The 24-week treatment period was completed by 85% of alirocumab and 86% of ezetimibepatients. 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 ezetimibepatients, 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.
Authors: Alessandro Squizzato; Matteo Basilio Suter; Marta Nerone; Robert Patrick Giugliano; Francesco Dentali; Andrea Maria Maresca; Leonardo Campiotti; Anna Maria Grandi; Luigina Guasti Journal: Intern Emerg Med Date: 2017-07-10 Impact factor: 3.397
Authors: Harold Bays; Daniel Gaudet; Robert Weiss; Juan Lima Ruiz; Gerald F Watts; Ioanna Gouni-Berthold; Jennifer Robinson; Jian Zhao; Corinne Hanotin; Stephen Donahue Journal: J Clin Endocrinol Metab Date: 2015-06-01 Impact factor: 5.958