Proprotein convertase subtilisin/kexin type 9 inhibition as the next statin?

Despite the wide use of statins and other LDL-cholesterol (LDL-C)-lowering therapies, atherosclerotic cardiovascular disease remains an important cause of mortality and morbidity. Here, we discuss efficacy, side effects and convenience of current and future therapies inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9).

Clinical trials with mAbs administered every 2-4 weeks and small interfering RNAs given two to four times per year have consistently demonstrated substantial LDL-C-lowering (40-60%) and improved outcome when added to existing lipid-lowering therapies. Pleiotropic effects of PCSK9 inhibition are somewhat different from those observed with statin treatment as evidenced by reduced levels of triglycerides and lipoprotein(a) with no apparent effect on inflammatory markers in patients treated with PCSK9 inhibitors. Treatment with mAb and small interfering RNA are associated with a high-cost, however, small molecules and vaccines may improve cost and convenience if development of these are successful.

PCSK9 inhibitors are currently considered to be an add-on therapy and whether these drugs will be used as stand-alone and/or as a first choice is dependent on clinical readouts from ongoing and future trials, real-world evidence, convenience and treatment costs.