Endocrine Abstracts

Anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies are a new class of biological drugs that inhibit binding of PCSK9 to the LDL receptor, thus increasing LDL-receptor density and lowering circulating LDL-cholesterol (LDL-C), apo-B100 and Lp(a). Recently released guidelines on management of hyperlipidemia reinforced the attribute of statins as the mainstay of lipid-lowering medication in dyslipidemic at-risk individuals, as every 1.0 mmol/L reduction in LDL-C is associated with a corresponding 20–25% reduction in cardiovascular disease mortality and non-fatal myocardial infarction, in addition to non-LDL-C benefits. Clinical trials demonstrated the advantages of treating extreme risk patients to an LDL-C target <55mg/dl by high-intensity statin or add-on non-statin therapies; statin and ezetimibe or, based on outcomes from FOURIER (Further cardiovascular OUtcomes Research with PCSK9 Inhibition in subjects with Elevated Risk) and ODYSEEY clinical program and particularly when >25% additional lowering of LDL-C is required, the combination treatment of statin and PCSK9 inhibitors is suggested to accomplish lipid and cardiovascular goals in patients with or without diabetes. PCKS9 inhibitors are capable of further decreasing LDL-C to around 60% when added to maximum statin therapy, which translates for evolocumab into 1% reduction in atheroma volume and atheroma plaque regression in about two-thirds of patients. Therapeutic challenges posed by genetic, familial heterozygous or homozygous hypercholesterolemia might be overcome by adding to maximally tolerated statin therapy non-statin agents including PCSK9 inhibitors, although homozygous receptor negative hypercholesterolemia patients may not respond. As a class effect, PCSK9 inhibitors address dyslipidemia in statin intolerant patients, with evolocumab being slightly more effective compared to ezetimibe in terms of LDL-C reduction and with an overall good tolerability. Adverse effects (<2–5%) commonly include nasopharyngitis, muscle-related events, back and leg pain, arthralgia, headache. Conclusion: PCSK9 inhibitors represent a promising non-statin tool in lipid management to be considered in well-defined clinical circumstances.