title: Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: The ODYSSEY OPTIONS II randomized trial.
abstract: OBJECTIVE
  To compare lipid-lowering efficacy of adding alirocumab to rosuvastatin versus other treatment strategies (NCT01730053).
  
  
  METHODS
  Patients receiving baseline rosuvastatin regimens (10 or 20 mg) were randomized to: add-on alirocumab 75 mg every-2-weeks (Q2W) (1-mL subcutaneous injection via pre-filled pen); add-on ezetimibe 10 mg/day; or double-dose rosuvastatin. Patients had cardiovascular disease (CVD) and low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL (1.8 mmol/L) or CVD risk factors and LDL-C ≥100 mg/dL (2.6 mmol/L). In the alirocumab group, dose was blindly increased at Week 12 to 150 mg Q2W (also 1-mL volume) in patients not achieving their LDL-C target. Primary endpoint was percent change in calculated LDL-C from baseline to 24 weeks (intent-to-treat).
  
  
  RESULTS
  305 patients were randomized. In the baseline rosuvastatin 10 mg group, significantly greater LDL-C reductions were observed with add-on alirocumab (-50.6%) versus ezetimibe (-14.4%; p < 0.0001) and double-dose rosuvastatin (-16.3%; p < 0.0001). In the baseline rosuvastatin 20 mg group, LDL-C reduction with add-on alirocumab was -36.3% compared with -11.0% with ezetimibe and -15.9% with double-dose rosuvastatin (p = 0.0136 and 0.0453, respectively; pre-specified threshold for significance p < 0.0125). Overall, ∼80% alirocumab patients were maintained on 75 mg Q2W. Of alirocumab-treated patients, 84.9% and 66.7% in the baseline rosuvastatin 10 and 20 mg groups, respectively, achieved risk-based LDL-C targets. Treatment-emergent adverse events occurred in 56.3% of alirocumab patients versus 53.5% ezetimibe and 67.3% double-dose rosuvastatin (pooled data).
  
  
  CONCLUSIONS
  The addition of alirocumab to rosuvastatin provided incremental LDL-C lowering versus adding ezetimibe or doubling the rosuvastatin dose.
authors.affiliation: Point Médical, Dijon, France. Electronic address: michelfarnier@nerim.net.
authors.forename: Michel
authors.initials: M
authors.lastname: Farnier
authors.affiliation: Baylor College of Medicine, Houston, TX, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Jones
authors.affiliation: Radiant Research - Phoenix SE, Chandler, AZ, USA.
authors.forename: Randall
authors.initials: R
authors.lastname: Severance
authors.affiliation: Università di Palermo - Policlinico "P. Giaccone", Palermo, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Averna
authors.affiliation: Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Steinhagen-Thiessen
authors.affiliation: University of Dundee, Dundee, Scotland.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Colhoun
authors.affiliation: Regeneron Pharmaceuticals, Inc. Tarrytown, NY, USA.
authors.forename: Yunling
authors.initials: Y
authors.lastname: Du
authors.affiliation: Sanofi, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Hanotin
authors.affiliation: Regeneron Pharmaceuticals, Inc. Tarrytown, NY, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Donahue
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000008:administration & dosage; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000097:blood* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D007279:Injections, Subcutaneous; D012189:Retrospective Studies; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000068718:Rosuvastatin Calcium; D000069438:Ezetimibe; C571059:alirocumab
keywords: Alirocumab; Ezetimibe; Low-density lipoprotein cholesterol; Monoclonal antibody; PCSK9; Rosuvastatin