Current atherosclerosis reports · 2022
Lp(a): a New Pathway to Target?
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Nurmohamed Nick S, Kraaijenhof Jordan M, Stroes Erik S G
Аннотация
PURPOSE OF REVIEW: Over the past decades, genetic and observational evidence has positioned lipoprotein(a) as novel important and independent risk factor for cardiovascular disease (ASCVD) and aortic valve stenosis.
RECENT FINDINGS: As Lp(a) levels are determined genetically, lifestyle interventions have no effect on Lp(a)-mediated ASCVD risk. While traditional low-density lipoprotein cholesterol (LDL-C) can now be effectively lowered in the vast majority of patients, current lipid lowering therapies have no clinically relevant Lp(a) lowering effect. There are multiple Lp(a)-directed therapies in clinical development targeting LPA mRNA that have shown to lower Lp(a) plasma levels for up to 90%: pelacarsen, olpasiran, and SLN360. Pelacarsen is currently investigated in a phase 3 cardiovascular outcome trial expected to finish in 2024, while olpasiran is about to proceed to phase 3 and SLN360's phase 1 outcomes were recently published. If proven efficacious, Lp(a) will soon become the next pathway to target in ASCVD risk management.
RECENT FINDINGS: As Lp(a) levels are determined genetically, lifestyle interventions have no effect on Lp(a)-mediated ASCVD risk. While traditional low-density lipoprotein cholesterol (LDL-C) can now be effectively lowered in the vast majority of patients, current lipid lowering therapies have no clinically relevant Lp(a) lowering effect. There are multiple Lp(a)-directed therapies in clinical development targeting LPA mRNA that have shown to lower Lp(a) plasma levels for up to 90%: pelacarsen, olpasiran, and SLN360. Pelacarsen is currently investigated in a phase 3 cardiovascular outcome trial expected to finish in 2024, while olpasiran is about to proceed to phase 3 and SLN360's phase 1 outcomes were recently published. If proven efficacious, Lp(a) will soon become the next pathway to target in ASCVD risk management.