Efficacy and safety of Alirocumab were compared with Ezetimibe ( Ezetrol, Zetia ) in hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy.
In a phase 3, randomized, double-blind, double-dummy study, patients ( low-density lipoprotein cholesterol [ LDL-C ] 100-190mg/dL, 10-year risk of fatal cardiovascular events greater than or equal to 1% - less than 5% [ systemic coronary risk estimation ] ) were randomized to Ezetimibe 10mg/day ( n=51 ) or Alirocumab 75mg subcutaneously ( via 1-mL autoinjector ) every 2weeks ( Q2W ) ( n=52 ), with dose up-titrated to 150mg Q2W ( also 1mL ) at week 12 if week 8 LDL-C was greater than or equal to 70mg/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.
Mean baseline LDL-cholesterol levels were 141.1 mg/dL ( Alirocumab ) and 138.3 mg/dL ( Ezetimibe ).
The 24-week treatment period was completed by 85% of Alirocumab and 86% of Ezetimibe patients. Least squares mean LDL-C reductions were 47% with Alirocumab versus 16% with Ezetimibe ( ITT; p less than 0.0001 ) and 54% versus 17% ( on-treatment; p less than 0.0001 ).
At week 12, before up-titration, Alirocumab 75mg Q2W reduced LDL-C by 53% ( on-treatment ).
Injection site reactions were infrequent ( less than 2% and less than 4% of Alirocumab and Ezetimibe patients, respectively ).
In conclusion, Alirocumab has demonstrated significantly greater LDL-C lowering versus Ezetimibe after 24 weeks with the lower 75mg Q2W dose sufficient to provide greater than or equal to 50% LDL-C reduction in the majority of the patients.
Adverse events were comparable between groups. ( Xagena )
Roth EM et al, Int J Cardiol 2014; Epub ahead of print