Effect of alirocumab on specific lipoprotein non-high-density lipoprotein cholesterol and subfractions as measured by the vertical auto profile method: analysis of 3 randomized trials versus placebo

Lipids Health Dis. 2016 Feb 13:15:28. doi: 10.1186/s12944-016-0197-4.

Abstract

Background: The effect of alirocumab on potentially atherogenic lipoprotein subfractions was assessed in a post hoc analysis using the vertical auto profile (VAP) method.

Methods: Patients from three Phase II studies with low-density lipoprotein cholesterol (LDL-C) ≥ 2.59 mmol/L (100 mg/dL) at baseline on stable statin therapy were randomised to receive subcutaneous alirocumab 50-150 mg every 2 weeks (Q2W) or 150-300 mg every 4 weeks (according to study) or placebo for 8-12 weeks. Samples from patients treated with alirocumab 150 mg Q2W (n = 74; dose common to all three trials) or placebo (n = 71) were analysed by VAP. Percent change in lipoprotein subfractions with alirocumab vs. placebo was analysed at Weeks 6, 8 or 12 using analysis of covariance.

Results: Alirocumab significantly reduced LDL-C and the cholesterol content of subfractions LDL1, LDL2 and LDL3+4. Significant reductions were also observed in triglycerides, apolipoproteins CII and CIII and the cholesterol content of very low-density, intermediate-density, and remnant lipoproteins.

Conclusion: Alirocumab achieved reductions across a spectrum of atherogenic lipoproteins in patients receiving background statin therapy.

Trial registration: Clinicaltrials.gov identifiers: NCT01288443, NCT01288469, NCT01266876.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Cholesterol, LDL
  • Double-Blind Method
  • Female
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy
  • Lipid Metabolism / drug effects
  • Lipoproteins / blood*
  • Lipoproteins, HDL / blood
  • Lipoproteins, VLDL / blood
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Triglycerides / blood

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Cholesterol, LDL
  • Lipoproteins
  • Lipoproteins, HDL
  • Lipoproteins, VLDL
  • Triglycerides
  • alirocumab

Associated data

  • ClinicalTrials.gov/NCT01266876
  • ClinicalTrials.gov/NCT01288443
  • ClinicalTrials.gov/NCT01288469