title: Alirocumab as Add-On to Atorvastatin Versus Other Lipid Treatment Strategies: ODYSSEY OPTIONS I Randomized Trial.
abstract: BACKGROUND
  Despite current standard of care, many patients at high risk of cardiovascular disease (CVD) still have elevated low-density lipoprotein cholesterol (LDL-C) levels. Alirocumab is a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9.
  
  
  OBJECTIVE
  The objective of the study was to compare the LDL-C-lowering efficacy of adding alirocumab vs other common lipid-lowering strategies.
  
  
  METHODS
  Patients (n = 355) with very high CVD risk and LDL-C levels of 70 mg/dL or greater or high CVD risk and LDL-C of 100 mg/dL or greater on baseline atorvastatin 20 or 40 mg were randomized to one of the following: 1) add-on alirocumab 75 mg every 2 weeks (Q2W) sc; 2) add-on ezetimibe 10 mg/d; 3) double atorvastatin dose; or 4) for atorvastatin 40 mg regimen only, switch to rosuvastatin 40 mg. For patients not achieving protocol-defined LDL-C goals, the alirocumab dose was increased (blinded) at week 12 to 150 mg Q2W.
  
  
  METHODS
  The primary end point was percentage change in calculated LDL-C from baseline to 24 weeks (intent to treat).
  
  
  RESULTS
  Among atorvastatin 20 and 40 mg regimens, respectively, add-on alirocumab reduced LDL-C levels by 44.1% and 54.0% (P < .001 vs all comparators); add-on ezetimibe, 20.5% and 22.6%; doubling of atorvastatin dose, 5.0% and 4.8%; and switching atorvastatin 40 mg to rosuvastatin 40 mg, 21.4%. Most alirocumab-treated patients (87.2% and 84.6%) achieved their LDL-C goals. Most alirocumab-treated patients (86%) maintained their 75-mg Q2W regimen. Treatment-emergent adverse events occurred in 65.4% of alirocumab patients vs 64.4% ezetimibe and 63.8% double atorvastatin/switch to rosuvastatin (data were pooled).
  
  
  CONCLUSIONS
  Adding alirocumab to atorvastatin provided significantly greater LDL-C reductions vs adding ezetimibe, doubling atorvastatin dose, or switching to rosuvastatin and enabled greater LDL-C goal achievement.
authors.affiliation: Louisville Metabolic and Atherosclerosis Research Center (H.B.), Louisville, Kentucky 40213; ECOGENE-21 Clinical Trial Center and Department of Medicine (D.G.), Université de Montréal, Chicoutimi, Québec, Canada G7H 5H6; Maine Research Associates (R.W.), Auburn, Maine 04210; Lipid and Vascular Research Unit (J.L.R.), University Hospital Vall d'Hebron, 8035 Barcelona, Spain; Lipid Disorders Clinic (G.F.W.), Centre for Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6009, Australia; Center for Endocrinology, Diabetes and Preventive Medicine (I.G.-B.), University of Cologne, 50923 Cologne, Germany; University of Iowa (J.R.), Iowa City, Iowa 52242; Regeneron Pharmaceuticals, Inc (J.Z., S.D.), Tarrytown, New York 10591; and Sanofi (C.H.), 75014 Paris, France.
authors.forename: Harold
authors.initials: H
authors.lastname: Bays
authors.affiliation: Louisville Metabolic and Atherosclerosis Research Center (H.B.), Louisville, Kentucky 40213; ECOGENE-21 Clinical Trial Center and Department of Medicine (D.G.), Université de Montréal, Chicoutimi, Québec, Canada G7H 5H6; Maine Research Associates (R.W.), Auburn, Maine 04210; Lipid and Vascular Research Unit (J.L.R.), University Hospital Vall d'Hebron, 8035 Barcelona, Spain; Lipid Disorders Clinic (G.F.W.), Centre for Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6009, Australia; Center for Endocrinology, Diabetes and Preventive Medicine (I.G.-B.), University of Cologne, 50923 Cologne, Germany; University of Iowa (J.R.), Iowa City, Iowa 52242; Regeneron Pharmaceuticals, Inc (J.Z., S.D.), Tarrytown, New York 10591; and Sanofi (C.H.), 75014 Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.affiliation: Louisville Metabolic and Atherosclerosis Research Center (H.B.), Louisville, Kentucky 40213; ECOGENE-21 Clinical Trial Center and Department of Medicine (D.G.), Université de Montréal, Chicoutimi, Québec, Canada G7H 5H6; Maine Research Associates (R.W.), Auburn, Maine 04210; Lipid and Vascular Research Unit (J.L.R.), University Hospital Vall d'Hebron, 8035 Barcelona, Spain; Lipid Disorders Clinic (G.F.W.), Centre for Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6009, Australia; Center for Endocrinology, Diabetes and Preventive Medicine (I.G.-B.), University of Cologne, 50923 Cologne, Germany; University of Iowa (J.R.), Iowa City, Iowa 52242; Regeneron Pharmaceuticals, Inc (J.Z., S.D.), Tarrytown, New York 10591; and Sanofi (C.H.), 75014 Paris, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Weiss
authors.affiliation: Louisville Metabolic and Atherosclerosis Research Center (H.B.), Louisville, Kentucky 40213; ECOGENE-21 Clinical Trial Center and Department of Medicine (D.G.), Université de Montréal, Chicoutimi, Québec, Canada G7H 5H6; Maine Research Associates (R.W.), Auburn, Maine 04210; Lipid and Vascular Research Unit (J.L.R.), University Hospital Vall d'Hebron, 8035 Barcelona, Spain; Lipid Disorders Clinic (G.F.W.), Centre for Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6009, Australia; Center for Endocrinology, Diabetes and Preventive Medicine (I.G.-B.), University of Cologne, 50923 Cologne, Germany; University of Iowa (J.R.), Iowa City, Iowa 52242; Regeneron Pharmaceuticals, Inc (J.Z., S.D.), Tarrytown, New York 10591; and Sanofi (C.H.), 75014 Paris, France.
authors.forename: Juan Lima
authors.initials: JL
authors.lastname: Ruiz
authors.affiliation: Louisville Metabolic and Atherosclerosis Research Center (H.B.), Louisville, Kentucky 40213; ECOGENE-21 Clinical Trial Center and Department of Medicine (D.G.), Université de Montréal, Chicoutimi, Québec, Canada G7H 5H6; Maine Research Associates (R.W.), Auburn, Maine 04210; Lipid and Vascular Research Unit (J.L.R.), University Hospital Vall d'Hebron, 8035 Barcelona, Spain; Lipid Disorders Clinic (G.F.W.), Centre for Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6009, Australia; Center for Endocrinology, Diabetes and Preventive Medicine (I.G.-B.), University of Cologne, 50923 Cologne, Germany; University of Iowa (J.R.), Iowa City, Iowa 52242; Regeneron Pharmaceuticals, Inc (J.Z., S.D.), Tarrytown, New York 10591; and Sanofi (C.H.), 75014 Paris, France.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.affiliation: Louisville Metabolic and Atherosclerosis Research Center (H.B.), Louisville, Kentucky 40213; ECOGENE-21 Clinical Trial Center and Department of Medicine (D.G.), Université de Montréal, Chicoutimi, Québec, Canada G7H 5H6; Maine Research Associates (R.W.), Auburn, Maine 04210; Lipid and Vascular Research Unit (J.L.R.), University Hospital Vall d'Hebron, 8035 Barcelona, Spain; Lipid Disorders Clinic (G.F.W.), Centre for Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6009, Australia; Center for Endocrinology, Diabetes and Preventive Medicine (I.G.-B.), University of Cologne, 50923 Cologne, Germany; University of Iowa (J.R.), Iowa City, Iowa 52242; Regeneron Pharmaceuticals, Inc (J.Z., S.D.), Tarrytown, New York 10591; and Sanofi (C.H.), 75014 Paris, France.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Gouni-Berthold
authors.affiliation: Louisville Metabolic and Atherosclerosis Research Center (H.B.), Louisville, Kentucky 40213; ECOGENE-21 Clinical Trial Center and Department of Medicine (D.G.), Université de Montréal, Chicoutimi, Québec, Canada G7H 5H6; Maine Research Associates (R.W.), Auburn, Maine 04210; Lipid and Vascular Research Unit (J.L.R.), University Hospital Vall d'Hebron, 8035 Barcelona, Spain; Lipid Disorders Clinic (G.F.W.), Centre for Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6009, Australia; Center for Endocrinology, Diabetes and Preventive Medicine (I.G.-B.), University of Cologne, 50923 Cologne, Germany; University of Iowa (J.R.), Iowa City, Iowa 52242; Regeneron Pharmaceuticals, Inc (J.Z., S.D.), Tarrytown, New York 10591; and Sanofi (C.H.), 75014 Paris, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Robinson
authors.affiliation: Louisville Metabolic and Atherosclerosis Research Center (H.B.), Louisville, Kentucky 40213; ECOGENE-21 Clinical Trial Center and Department of Medicine (D.G.), Université de Montréal, Chicoutimi, Québec, Canada G7H 5H6; Maine Research Associates (R.W.), Auburn, Maine 04210; Lipid and Vascular Research Unit (J.L.R.), University Hospital Vall d'Hebron, 8035 Barcelona, Spain; Lipid Disorders Clinic (G.F.W.), Centre for Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6009, Australia; Center for Endocrinology, Diabetes and Preventive Medicine (I.G.-B.), University of Cologne, 50923 Cologne, Germany; University of Iowa (J.R.), Iowa City, Iowa 52242; Regeneron Pharmaceuticals, Inc (J.Z., S.D.), Tarrytown, New York 10591; and Sanofi (C.H.), 75014 Paris, France.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Louisville Metabolic and Atherosclerosis Research Center (H.B.), Louisville, Kentucky 40213; ECOGENE-21 Clinical Trial Center and Department of Medicine (D.G.), Université de Montréal, Chicoutimi, Québec, Canada G7H 5H6; Maine Research Associates (R.W.), Auburn, Maine 04210; Lipid and Vascular Research Unit (J.L.R.), University Hospital Vall d'Hebron, 8035 Barcelona, Spain; Lipid Disorders Clinic (G.F.W.), Centre for Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6009, Australia; Center for Endocrinology, Diabetes and Preventive Medicine (I.G.-B.), University of Cologne, 50923 Cologne, Germany; University of Iowa (J.R.), Iowa City, Iowa 52242; Regeneron Pharmaceuticals, Inc (J.Z., S.D.), Tarrytown, New York 10591; and Sanofi (C.H.), 75014 Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Hanotin
authors.affiliation: Louisville Metabolic and Atherosclerosis Research Center (H.B.), Louisville, Kentucky 40213; ECOGENE-21 Clinical Trial Center and Department of Medicine (D.G.), Université de Montréal, Chicoutimi, Québec, Canada G7H 5H6; Maine Research Associates (R.W.), Auburn, Maine 04210; Lipid and Vascular Research Unit (J.L.R.), University Hospital Vall d'Hebron, 8035 Barcelona, Spain; Lipid Disorders Clinic (G.F.W.), Centre for Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6009, Australia; Center for Endocrinology, Diabetes and Preventive Medicine (I.G.-B.), University of Cologne, 50923 Cologne, Germany; University of Iowa (J.R.), Iowa City, Iowa 52242; Regeneron Pharmaceuticals, Inc (J.Z., S.D.), Tarrytown, New York 10591; and Sanofi (C.H.), 75014 Paris, France.
authors.forename: Stephen
authors.initials: S
authors.lastname: Donahue
mesh_terms: D000368:Aged; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D000069059:Atorvastatin; D001384:Azetidines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000097:blood; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D000069438:Ezetimibe; C571059:alirocumab