Emerging pharmacological strategies in lipoprotein(a) reduction

Background: Lipoprotein(a) (Lp(a)) is an low-density lipoprotein (LDL)-like particle whose elevation is considered a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis. Currently, there are no published clinical trials showing whether Lp(a) lowering in conjunction with optimal LDL cholesterol control reduces ASCVD risk. Methods: Clinicaltrials.gov, an online database for clinical research studies, was used to identify ongoing clinical trials studying targeted Lp(a) lowering pharmacotherapy as of May 2025. Twelve clinical studies met the criteria and were included in this summary. Results: The three large, multicenter phase 3 outcome trials evaluating clinical cardiovascular disease endpoints of major adverse cardiac event (MACE) are Lp(a)HORIZON (NCT04023552), OCEAN(a) (NCT05581303), and ACCLAIM-Lpa(a) (NCT06292013), which investigate pelacarsen, olpasiran, and lepodisiran, respectively. Other phase 2 and phase 3 trials are also under way. Conclusion: Results from upcoming trials will inform us whether Lp(a) reductions translate to improved cardiovascular clinical outcomes.