title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01644188.
authors: Harvard Clinical Research Institute, 930 W. Commonwealth Ave, Boston, MA 02215, USA christopher.cannon@hcri.harvard.edu.
authors: Christopher P
authors: CP
authors: Cannon
authors: Department of Endocrinology, L'Institut du Thorax, CHU de Nantes, Nantes, France.
authors: Bertrand
authors: B
authors: Cariou
authors: Division of Lipidology, Department of Medicine, University of Cape Town and MRC Cape Heart Group, Cape Town, South Africa.
authors: Dirk
authors: D
authors: Blom
authors: Virginia Commonwealth University and National Clinical Research, Inc., Richmond, VA, USA.
authors: James M
authors: JM
authors: McKenney
authors: Sanofi, Paris, France.
authors: Christelle
authors: C
authors: Lorenzato
authors: Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
authors: Robert
authors: R
authors: Pordy
authors: Sanofi, Bridgewater, NJ, USA.
authors: Umesh
authors: U
authors: Chaudhari
authors: University of Dundee, Dundee, UK.
authors: Helen M
authors: HM
authors: Colhoun
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000378:metabolism; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000069438:Ezetimibe / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy*; D007279:Injections, Subcutaneous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe; C571059:alirocumab
keywords: Alirocumab; Ezetimibe; Low-Density Lipoprotein Cholesterol; Monoclonal antibody