SAT-260 Comparative Efficacy of Olpasiran and Zerlasiran in Reducing Lipoprotein(a) Levels: A Network Meta-Analysis of Clinical Trials

Abstract Disclosure: J. Abu Zayed: None. M. Hdaib: None. A. Jaber: None. H. Ayesh: None. Introduction: Elevated lipoprotein(a) [Lp(a)] levels are a well-established, independent risk factor for cardiovascular diseases, including coronary artery disease, ischemic stroke, and heart failure. Traditional lipid-lowering therapies have limited effects on Lp(a) levels, creating a demand for novel, targeted treatments. RNA-based therapies such as Olpasiran and Zerlasiran represent promising advancements in managing Lp(a)-associated cardiovascular risk. This network meta-analysis compares the efficacy of these agents in reducing Lp(a) levels, providing critical insights to guide treatment strategies. Methods: A systematic search of PubMed, Web of Science, Cochrane, and Scopus databases was conducted to identify randomized controlled trials evaluating Olpasiran and Zerlasiran. Of six studies screened, four trials met the inclusion criteria. Random-effects models were used to calculate treatment efficacy, reported as mean differences (MD) with 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic, and subgroup analyses were conducted to explore potential sources of variability. Results: Olpasiran demonstrated a significant reduction in Lp(a) levels compared to placebo (MD: -98.34 nmol/L, 95% CI: [-102.75; -93.92], p < 0.0001) with moderate heterogeneity (I² = 41.9%). Zerlasiran also achieved a significant reduction in Lp(a) levels compared to placebo (MD: -89.03 nmol/L, 95% CI: [-93.53; -84.53], p < 0.0001), though with higher heterogeneity (I² = 69.5%). Direct comparisons suggested Olpasiran may offer slightly greater efficacy in lowering Lp(a). In addition, both agents reduced LDL cholesterol and ApoB levels. For LDL cholesterol, Olpasiran showed a modest reduction (MD: -10.22 mg/dL, 95% CI: [-33.50; 13.06], p = 0.39), while Zerlasiran achieved a more substantial but borderline significant effect (MD: -23.94 mg/dL, 95% CI: [-48.11; -0.22], p = 0.05). Both therapies significantly reduced ApoB levels (Olpasiran MD: -15.30 mg/dL, p < 0.001; Zerlasiran MD: -19.18 mg/dL, p < 0.0001). Conclusions: Both Olpasiran and Zerlasiran are highly effective in reducing Lp(a) levels, with Olpasiran showing a numerically greater reduction. These findings underscore the therapeutic potential of RNA-based agents in addressing elevated Lp(a), a critical modifiable risk factor for cardiovascular diseases. Presentation: Saturday, July 12, 2025