Efficacy of alirocumab according to background statin type and dose: pooled analysis of 8 ODYSSEY Phase 3 clinical trials

Sci Rep. 2017 Apr 4:7:45788. doi: 10.1038/srep45788.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Anticholesteremic Agents / therapeutic use*
  • Atorvastatin / administration & dosage
  • Atorvastatin / therapeutic use
  • Cholesterol, LDL / drug effects*
  • Clinical Trials as Topic
  • Ezetimibe / administration & dosage
  • Ezetimibe / therapeutic use
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypercholesterolemia / drug therapy
  • Male
  • Middle Aged
  • Proprotein Convertase 9
  • Rosuvastatin Calcium / administration & dosage
  • Rosuvastatin Calcium / therapeutic use
  • Simvastatin / administration & dosage
  • Simvastatin / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Anticholesteremic Agents
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Rosuvastatin Calcium
  • Atorvastatin
  • Simvastatin
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Ezetimibe
  • alirocumab