A Comprehensive Review of PCSK9 Inhibitor Therapy

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a key component of lipid-lowering therapies for atherosclerotic cardiovascular disease risk management in high-risk primary and secondary prevention populations. PCSK9 monoclonal antibodies such as evolocumab and alirocumab were the first agents approved and are the preferred agents given phase 3 trial data supporting improved cardiovascular outcomes. Subgroup analyses of these trials have highlighted high-risk populations that may especially benefit from PCSK9 inhibitor therapy, although demographic disparities persist regarding their implementation. Additional injectable agents with less-frequent dosing schedules have been developed, such as the small-interfering RNA inclisiran, though they lack data regarding cardiovascular outcomes. Oral agents are also in development, with promising data recently presented regarding enlicitide. Additionally, recent trials provide evidence supporting expanded indications for high-risk primary prevention. This review summarizes currently available and investigational PCSK9-targed therapies and examines evidence guiding their clinical implementation.