PCSK9 inhibition
Review traces why statins raise Lp(a) while PCSK9 inhibitors lower it, and what that means for residual cardiovascular risk (Clin Chim Acta 2025)
Original title: Lipoprotein(a) in atherosclerotic cardiovascular disease and proprotein convertase subtilisin/kexin-type 9 inhibitors
This systematic review examines the relationship between Lp(a), atherosclerotic cardiovascular disease, and PCSK9 inhibitors. Statins, the mainstay ASCVD therapy, lower LDL-C but concurrently raise plasma Lp(a), contributing to residual cardiovascular risk that persists despite LDL-C control. PCSK9 inhibitors, by contrast, reduce both LDL-C and Lp(a), a combination believed to further lower residual risk, though the mechanism by which they reduce Lp(a) specifically remains unresolved. The review traces the history, current evidence and outstanding clinical limitations of PCSK9 inhibitors as an Lp(a)-lowering strategy, framing the unresolved mechanism as a key open question for the field.
Original abstract
High plasma lipoprotein(a) (Lp(a)) levels increase the cardiovascular risk in populations with atherosclerotic cardiovascular disease (ASCVD). Apolipoprotein (a) [apo(a)], a unique protein component of Lp(a), plays an important role in the pathogenesis of atherosclerosis. Statins, the primary medication in managing ASCVD, lower low-density lipoprotein cholesterol (LDL-C) but concurrently elevate plasma Lp(a) levels, contributing to an increased residual cardiovascular risk. In turn, proprotein convertase subtilisin/kexin-type 9 (PCSK9) inhibitors, a novel class of LDL-C lowering drugs, effectively reduce plasma Lp(a) levels, which is believed to decrease residual cardiovascular risk. However, the mechanism by which PCSK9 inhibitors reduce Lp(a) levels remains unknown. In addition, there are some clinical limitations of PCSK9 inhibitors. Here, we systematically review the past, present, and prospects of studies pertaining to Lp(a), PCSK9 inhibitors, and ASCVD.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.