Lowering of Lipoprotein(a) with Olpasiran

Elevated lipoprotein(a) [Lp(a)] is associated with an increased risk of aortic stenosis and Atherosclerotic Cardiovascular Disease (ASCVD), including myocardial infarction. Therefore, Lp(a) has emerged as a potential target for reducing residual cardiovascular risk. Conventional lipid-lowering interventions, including lifestyle modifications such as diet and exercise and statin therapies, have not been shown to effectively reduce Lp(a) levels. Ezetimibe, which inhibits cholesterol absorption and can reduce LDL-C, does not significantly affect Lp(a) levels, even when used in combination with statins. PCSK9 inhibitors have been found to reduce Lp(a) levels but to a lesser extent than their effect on LDL-C, and the clinical significance of the 15- 20% reduction in Lp(a) they offer is not entirely clear. Emerging therapies to lower Lp(a) focus on inhibiting apo(a) synthesis. One such agent is Olpasiran, a small interfering RNA (siRNA) that degrades apo(a) mRNA, preventing subsequent production of the protein. Its efficacy was studied in the OCEAN(a)-DOSE trial that included patients with established ASCVD and Lp(a) > 150 nmol/L and demonstrated greater than 95% reduction in Lp(a). A phase 3 outcomes trial is currently underway. In this review article, we delve further into lowering of Lp(a) with Olpasiran by detailing its pharmacological properties, its efficacy based on data from clinical trials, and ongoing research. The study also contextualizes it within the broader therapeutic landscape alongside other agents targeting Lp(a), such as Pelacarsen and Lepodisiran.