Lp(a) is moving from a passive risk marker to an active therapeutic target in acute coronary syndromes, as ASOs and siRNAs enter phase 3, a review (Curr Pharm Des 2023)

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in Western societies, despite the significant advances that have improved primary and secondary prevention. Hence, several novel biomarkers have been identified as potential diagnostic and therapeutic targets which could improve outcomes even when traditional risk factors are well-controlled. Lipoprotein (a) [Lp(a)] has pro-atherogenic, pro-thrombotic, and pro-inflammatory properties, and its levels are relatively constant and genetically predetermined. Several epidemiological studies have associated high Lp(a) with increased risk for acute coronary syndromes (ACS) even when other CAD risk factors are included in the multivariate analysis. However, until recently, specific therapeutic options targeting Lp(a) were not associated, and thus, Lp(a) is currently used as a risk and treatment modifying biomarker with guidelines suggesting the intensified treatment of low-density lipoprotein in intermediate- to-high-risk patients with increased Lp(a) levels. Lately, specific treatment options targeting Lp(a) have become available and include antisense oligonucleotides and small-interfering RNA, which induce a robust reduction of Lp(a). Results of ongoing phase-3 trials will answer whether Lp(a) will become a biomarker specifically treated to reduce the burden of cardiovascular mortality. The scope of this review article is to present the current evidence regarding the use of Lp(a) as a biomarker, predictive of increased CAD risk, and to discuss the future perspectives on pharmaceutical reduction of Lp(a) as a therapeutic target in high-risk patients.