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Int J Cardiol. 2014 Sep;176(1):55-61. doi: 10.1016/j.ijcard.2014.06.049. Epub 2014 Jul 2.

Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial.

Author information

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.

KEYWORDS:

Alirocumab; Cholesterol-lowering drugs; Hypercholesterolemia; LDL-C; Monoclonal antibodies; PCSK9

PMID:
25037695
DOI:
10.1016/j.ijcard.2014.06.049
[Indexed for MEDLINE]
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