Ups and downs in PCSK9 inhibition in the cardiovascular arena: a review

Abstract

Purpose of review This article reviews PCSK9 inhibitors (PCSK9i) with a focus on clinically relevant studies published in the last 18 months. Recent findings Prespecified subgroup evaluations, secondary analyses, and open-label extension studies from the two landmark trials, FOURIER and ODYSSEY Outcomes, have provided new data on the safety and efficacy of the monoclonal PCSK9 antibodies evolocumab and alirocumab. Recent studies of PCSK9i early in ACS and post percutaneous coronary intervention have explored early effects on biomarkers and plaque morphology with various imaging modalities. Two large outcome trials with PCSK9i in lower risk patients without prior myocardial infarction or stroke are ongoing and could expand the eligible population for these potent therapies. Additionally, novel methods to inhibit PCSK9 using oral administration, vaccination, and gene therapy are in various stages of clinical development. Summary PCSK9i represent a potent class of lipid-lowering therapies that are well tolerated and effective in a wide group of patients with high-risk atherosclerotic cardiovascular disease. Ongoing studies of PCSK9i in patients at lower risk and with acute myocardial infarction have the potential to broaden their indication. Alternative methods of PCSK9i are being evaluated and could provide easier and less expensive options for this important class of medication.

PCSK9-directed therapies: an update

“…Lastly, several novel approaches of PCSK9 inhibition are at different stages of development and may be referred to as third-generation PCSK9 inhibitors [4]. This group encompasses different strategies from orally available drugs to gene editing as 'once-and-done' approach [5,6].…”