title: Efficacy of alirocumab according to background statin type and dose: pooled analysis of 8 ODYSSEY Phase 3 clinical trials.
abstract: Low-density lipoprotein cholesterol (LDL-C) reductions with the PCSK9 monoclonal antibody alirocumab may be affected by background statin dose due to increased PCSK9 levels with higher statin doses. Data from 8 Phase 3 trials conducted with background statin (n = 4629) were pooled by alirocumab dose (75 or 150 mg every 2 weeks) and control (placebo/ezetimibe), and analyzed by background statin type/dose. Overall, 58.4% received high-dose statins (atorvastatin 40-80 mg, rosuvastatin 20-40 mg, simvastatin 80 mg), 28.6% moderate-dose statins (atorvastatin 20-<40 mg, rosuvastatin 10-<20 mg, simvastatin 40-<80 mg), and 12.9% low-dose statins (atorvastatin <20 mg, rosuvastatin <10 mg, simvastatin <40 mg). Mean baseline PCSK9 levels were higher with high versus moderate and low statin doses (318.5 vs 280.6 ng/mL). Baseline LDL-C levels were similar across pools, regardless of statin intensity. No associations were observed between statin type/dose and LDL-C % change from baseline or % of patients achieving LDL-C goals at Week 24 for alirocumab versus control (interaction P-values non-significant). Incidence of adverse events was similar for alirocumab versus control, except for a higher rate of injection-site reactions with alirocumab. In summary, alirocumab provided consistent LDL-C reductions and was generally well tolerated independent of background statin type/dose.
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università di Milano and IRCCS Multimedica, Milan, Italy.
authors.forename: Alberico L
authors.initials: AL
authors.lastname: Catapano
authors.affiliation: Sanofi, Bridgewater, New Jersey, USA.
authors.forename: L Veronica
authors.initials: LV
authors.lastname: Lee
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Louie
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
authors.forename: Desmond
authors.initials: D
authors.lastname: Thompson
authors.affiliation: Clinique des Maladies Lipidiques, CHU de Québec-Université Laval, Québec, QC, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Bergeron
authors.affiliation: CHU de Nantes - Hôpital Nord Laennec, Saint-Herblain, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Krempf
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin / Q000008:administration & dosage / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000187:drug effects*; D002986:Clinical Trials as Topic; D000069438:Ezetimibe / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage / Q000627:therapeutic use; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D019821:Simvastatin; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D000069438:Ezetimibe; C571059:alirocumab