title: Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.
abstract: BACKGROUND
  Alirocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), has been shown to reduce low-density lipoprotein (LDL) cholesterol levels in patients who are receiving statin therapy. Larger and longer-term studies are needed to establish safety and efficacy.
  
  
  METHODS
  We conducted a randomized trial involving 2341 patients at high risk for cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or more and were receiving treatment with statins at the maximum tolerated dose (the highest dose associated with an acceptable side-effect profile), with or without other lipid-lowering therapy. Patients were randomly assigned in a 2:1 ratio to receive alirocumab (150 mg) or placebo as a 1-ml subcutaneous injection every 2 weeks for 78 weeks. The primary efficacy end point was the percentage change in calculated LDL cholesterol level from baseline to week 24.
  
  
  RESULTS
  At week 24, the difference between the alirocumab and placebo groups in the mean percentage change from baseline in calculated LDL cholesterol level was -62 percentage points (P<0.001); the treatment effect remained consistent over a period of 78 weeks. The alirocumab group, as compared with the placebo group, had higher rates of injection-site reactions (5.9% vs. 4.2%), myalgia (5.4% vs. 2.9%), neurocognitive events (1.2% vs. 0.5%), and ophthalmologic events (2.9% vs. 1.9%). In a post hoc analysis, the rate of major adverse cardiovascular events (death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization) was lower with alirocumab than with placebo (1.7% vs. 3.3%; hazard ratio, 0.52; 95% confidence interval, 0.31 to 0.90; nominal P=0.02).
  
  
  CONCLUSIONS
  Over a period of 78 weeks, alirocumab, when added to statin therapy at the maximum tolerated dose, significantly reduced LDL cholesterol levels. In a post hoc analysis, there was evidence of a reduction in the rate of cardiovascular events with alirocumab. (Funded by Sanofi and Regeneron Pharmaceuticals; ODYSSEY LONG TERM ClinicalTrials.gov number, NCT01507831.).
authors.affiliation: From the University of Iowa, Iowa City (J.G.R.); Point Médical, Dijon (M.F.), Centre Hospitalier Universitaire de Nantes-Hôpital Nord Laennec, Saint-Herblain (M.K.), University Hospital of Lille, Lille (G. Luc), and Sanofi, Chilly-Mazarin (C.L.) - all in France; Clinique des Maladies Lipidiques de Québec, Quebec, QC, Canada (J.B.); Università di Palermo-Policlinico P. Giaccone, Palermo, Italy (M.A.); the Department of Vascular Medicine, Academic Medical Center, Amsterdam (E.S.S., J.J.P.K.); Lipid Clinic, Oslo University Hospital, Oslo (G. Langslet); University of the Witwatersrand, Johannesburg (F.J.R.); Cardiovascular Center of Sarasota, Sarasota (M.E.S.), and Jacksonville Center for Clinical Research, Jacksonville (M.J.K.) - both in Florida; Westside Medical Associates of Los Angeles, Beverly Hills, CA (N.E.L.); Regeneron Pharmaceuticals, Tarrytown, NY (R.P.); and Sanofi, Bridgewater, NJ (U.C.).
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Robinson
authors.forename: Michel
authors.initials: M
authors.lastname: Farnier
authors.forename: Michel
authors.initials: M
authors.lastname: Krempf
authors.forename: Jean
authors.initials: J
authors.lastname: Bergeron
authors.forename: Gérald
authors.initials: G
authors.lastname: Luc
authors.forename: Maurizio
authors.initials: M
authors.lastname: Averna
authors.forename: Erik S
authors.initials: ES
authors.lastname: Stroes
authors.forename: Gisle
authors.initials: G
authors.lastname: Langslet
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Raal
authors.forename: Mahfouz
authors.initials: M
authors.lastname: El Shahawy
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Koren
authors.forename: Norman E
authors.initials: NE
authors.lastname: Lepor
authors.forename: Christelle
authors.initials: C
authors.lastname: Lorenzato
authors.forename: Robert
authors.initials: R
authors.lastname: Pordy
authors.forename: Umesh
authors.initials: U
authors.lastname: Chaudhari
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000097:blood*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C571059:alirocumab