Plasmatic and phenotypic effects with alirocumab, a PCSK9 inhibitor, in familial hypercholesterolemia treatment (FH)

Aim: FH therapy is based on HMG-CoA reductase inhibitors, Ezetimibe and apheresis. Recently, PCSK9 antagonists were introduced as an "add-on therapy" for severe hypercholesterolemia "resistant" to common therapies. Results: Patient 1 had arcus cornealis and tendinous xanthomata and premature CAD. Basal total cholesterol was 433 mg/dl, LDL-C mg/dl 364, triglicerides 180 mg/dl, HDL 31 mg/d, Lp(a) 95 mg/dl. Despite Atorvastatin (80 mg) and Ezetimibe (10 mg), LDL-C level was elevated (180 mg/dl). DLCN was 12. With Alirocumab (75 mg/ml) every 2 weeks, LDL-C reduced to 85 mg/dl. We doubled Alirocumab posology to 150 mg/dl twice a month. Xanthomata were significantly reduced, such as total and LDL cholesterol. Ă Patient 2 had premature CAD and lower limb arteries disease; DLCN score was 5. Despite Atorvastatin (40 mg) and Ezetimibe 10, total cholesterol was 217 mg/dl, LDL-C was not at goal (120 mg/dl). We added Alirocumab (75 mg/ ml) every 2 weeks. Total and LDL-C resulted notably decreased (LDL 3,6 mg/dl). Ezetimibe was discontinued and Atorvastatin reduced. Patient referred reduction of muscular pain after statin dosage reduction and the beginning of regular exercise. Patient 3 had premature CAD, LDL-C (222 mg/dl); despite Torvast 40 mg, Ezetimibe 10 mg and Esapent, we added Alirocumab 75 mg/ml twice a month with LDL-C reduction (54 mg/dl). No untoward effects were reported by the patients. Conclusions: Our group demonstrates a great interindividual variability to response to Alirocumab and regression of skin lipid lesions, never been observed during therapy with statins or other lipid-lowering treatments.