PCSK9 inhibitors and LDL reduction: pharmacology, clinical implications, and future perspectives

ABSTRACTIntroduction: PCSK9 inhibitors are monoclonal antibodies to proprotein convertase-subtilisin/kexin type 9 which significantly reduce LDL cholesterol concentration in vivo by inhibiting degradation of the LDL receptor in hepatocytes. The introduction of PCSK9 inhibitors heralded a new era of intensive LDL-C reduction with LDL-C concentrations lowered below levels ever thought possible with conventional treatments such as statins. With their introduction considerations regarding cost, clinical outcomes and long-term safety are paramount.Areas covered: This review examines the pharmacology of PCSK9 inhibitors and summarizes the current evidence base for use in clinical practice from an efficacy, safety, and cardiovascular outcome perspective including recently presented data on alirocumab. It also examines the potential role of these agents into the future. Potential issues with PCSK9 inhibitors are examined and future pharmacologic targets are examined including siRNA and PCSK9 vaccination.Expert co...