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Eur Heart J. 2015 May 14;36(19):1186-94. doi: 10.1093/eurheartj/ehv028. Epub 2015 Feb 16.

Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial.

Author information

1
Harvard Clinical Research Institute, 930 W. Commonwealth Ave, Boston, MA 02215, USA christopher.cannon@hcri.harvard.edu.
2
Department of Endocrinology, L'Institut du Thorax, CHU de Nantes, Nantes, France.
3
Division of Lipidology, Department of Medicine, University of Cape Town and MRC Cape Heart Group, Cape Town, South Africa.
4
Virginia Commonwealth University and National Clinical Research, Inc., Richmond, VA, USA.
5
Sanofi, Paris, France.
6
Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
7
Sanofi, Bridgewater, NJ, USA.
8
University of Dundee, Dundee, UK.

Abstract

AIMS:

To compare the efficacy [low-density lipoprotein cholesterol (LDL-C) lowering] and safety of alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin 9, compared with ezetimibe, as add-on therapy to maximally tolerated statin therapy in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia.

METHODS AND RESULTS:

COMBO II is a double-blind, double-dummy, active-controlled, parallel-group, 104-week study of alirocumab vs. ezetimibe. Patients (n = 720) with high cardiovascular risk and elevated LDL-C despite maximal doses of statins were enrolled (August 2012-May 2013). This pre-specified analysis was conducted after the last patient completed 52 weeks. Patients were randomized to subcutaneous alirocumab 75 mg every 2 weeks (plus oral placebo) or oral ezetimibe 10 mg daily (plus subcutaneous placebo) on a background of statin therapy. At Week 24, mean ± SE reductions in LDL-C from baseline were 50.6 ± 1.4% for alirocumab vs. 20.7 ± 1.9% for ezetimibe (difference 29.8 ± 2.3%; P < 0.0001); 77.0% of alirocumab and 45.6% of ezetimibe patients achieved LDL-C <1.8 mmol/L (P < 0.0001). Mean achieved LDL-C at Week 24 was 1.3 ± 0.04 mmol/L with alirocumab and 2.1 ± 0.05 mmol/L with ezetimibe, and were maintained to Week 52. Alirocumab was generally well tolerated, with no evidence of an excess of treatment-emergent adverse events.

CONCLUSION:

In patients at high cardiovascular risk with inadequately controlled LDL-C, alirocumab achieved significantly greater reductions in LDL-C compared with ezetimibe, with a similar safety profile.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT01644188.

KEYWORDS:

Alirocumab; Ezetimibe; Low-Density Lipoprotein Cholesterol; Monoclonal antibody

PMID:
25687353
PMCID:
PMC4430683
DOI:
10.1093/eurheartj/ehv028
[Indexed for MEDLINE]
Free PMC Article

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