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

Peter P. Toth, Sara C. Hamon, Steven R. Jones, Seth S. Martin, Parag H. Joshi, Krishnaji R. Kulkarni, Poulabi Banerjee, Corinne Hanotin, Eli M. Roth, James M. McKenney

The effect of alirocumab on potentially atherogenic lipoprotein subfractions was assessed in a post hoc analysis using the vertical auto profile (VAP) method. 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. 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. Alirocumab achieved reductions across a spectrum of atherogenic lipoproteins in patients receiving background statin therapy. Clinicaltrials.gov identifiers: NCT01288443 , NCT01288469 , NCT01266876.