Patients with heterozygous familial hypercholesterolemia benefit from PCSK9-antibody
Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 monoclonal antibody alirocumab vs placebo with heterozygous familial hypercholesterolemiaLiterature - Kastelein JJP, Hovingh GH, Langslet G et al. - J Clin Lipidol, 2017, DOI: http://dx.doi.org/10.1016/j.jacl.2016.12.004
- At week 12, before any dose increase, the mean percent change in LDL-C from baseline was -43.6% for patients on alirocumab 75 mg Q2W and -57.1% for those on 150 mg Q2W (placebo: 15.4% and 11.1%, respectively; all P < 0.0001 vs placebo).
- At week 12, 41.8% of patients on alirocumab 75 mg had their dose increased to 150 mg (75/150 mg) in a blinded manner.
- The mean percent change in LDL-C from baseline to week 24 was -48.8% for patients on alirocumab 75/150 mg (placebo: 17.1%) and -55.0% for those on alirocumab 150 mg Q2W (placebo: 11.3%; all P < 0.0001).
- The on-treatment least squares (LS) mean LDL-C levels were reduced to 69.1 and 75.6 mg/dL at week 24 in the alirocumab 75/150 mg and 150 mg groups, respectively. For weeks 24 to 78, LS mean LDL-C levels were 69.1-75.6 mg/dL (75/150 mg group) and 72.2-82.3 mg/dL (150 mg group).
- At week 24, most patients receiving alirocumab 75/150 mg (75.3%) or 150 mg (64.5%) achieved LDL-C levels of <70 or <100 mg/dL, depending on their CV risk (all P < 0.0001 vs placebo).
- Alirocumab 75/150 mg or 150 mg significantly reduced Apo B, non–HDL-C, total cholesterol, Lp(a), and fasting triglycerides levels vs placebo (all P < 0.0001), and significantly increased the HDL-C and Apo A1 levels vs placebo.
- In a multivariate analysis of two studies, the difference between LDL-C levels at baseline and the treatment goal, was the best predictor for the necessary dose adjustment from 75 mg to 150 mg at week 12 (P < 0.0001). Other predictors included a higher BMI and not taking other lipid-lowering treatments except statins.
- The rates of treatment-emergent adverse events were similar in alirocumab (80.5%) and placebo-treated patients (83.0%).
In four studies with HeFH patients, alirocumab resulted in significant LDL-C-lowering in most patients who were receiving the maximally tolerated dose of a statin, with or without other lipid-lowering therapies.