771-P: Meta-analysis of hsCRP's Effect on Cardiovascular Outcome among GLP-1RAs–Based Clinical Trials

Introduction and Objective: Certain cardiovascular outcome trials (CVOTs) indicated that GLP-1RAs may offer a potential cardiovascular protection effect, but the current results are inconsistent. GLP-1RAs have been shown to reduce hsCRP, despite the unclear relationship between hsCRP and cardiovascular risk. This meta-analysis evaluates whether the changes in hsCRP influence the 3-point major adverse cardiovascular events (3P-MACE) in CVOTs. Methods: A meta-analysis of randomized controlled trials comparing GLP-1RAs with placebo was performed. PubMed, Embase, Web of Science, and the Cochrane Library were searched up to Dec. 2024. The primary outcomes were changes in hsCRP and 3P-MACE. The value changes in hsCRP were analyzed by mean differences (MD) and standard deviations, and the percentage changes were analyzed by two sample t-test between studies w/ and w/o MACE protection. Linear regression was used to assess hsCRP's impact on cardiovascular mortality. Results: We identified 7 studies, 5 of which reported hsCRP value changes. Pooled result indicated that GLP-1RAs significantly reduced hsCRP compared to placebo, and the reduction was greater in cardiovascular protective studies (MD = -0.44, 95%CI -0.57 ~ -0.31) versus non-protective studies (MD = -0.38, 95%CI -0.44 ~ -0.32). A two sample t-test on hsCRP percentage changes from 5 studies (with available MACE data) showed a significant reduction in hsCRP in MACE-protective studies (P = 0.0386). Linear regression indicated that the hsCRP reduction didn’t improve mortality (P = 0.0551). Conclusion: This meta-analysis shows that GLP-1RAs could significantly reduce hsCRP, with a larger effect in MACE-protective studies. However, hsCRP's impact on cardiovascular mortality is marginally insignificant, possibly due to missing data and small sample sizes. It would be worthwhile to further explore the underlying mechanism of GLP-1RAs’ additional cardiovascular benefits by lowering hsCRP and improving inflammatory state. Disclosure L. Luo: None. Y. Luo: None. L. Ji: None.