APOE genotype and the effect of statins on lipid outcomes: A meta‐analysis

AIM: APOE genotype may affect statin therapy response. We conducted a meta-analysis to update and quantify this association across various outcomes. METHODS: We searched seven databases (MEDLINE, Scopus, Web of Science, the Cochrane Library, APA PsycINFO, CINAHL Plus and ClinicalTrials.gov) on 9 May 2024. Screening and data extraction were performed by two reviewers and a machine learning tool (ASReview). RESULTS: From 4352 de-duplicated records, 52 studies were included in the meta-analysis. Biomarkers analysed included low-density lipoprotein cholesterol (LDLC), total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol (HDLC). Compared to ε3 carriers, ε2 carriers showed greater reductions in LDLC in response to statin treatment (mean difference in percentage change: -2.98%, 95% CI: -5.88% to -0.08%) and similar reductions in TC (-2.73%, -5.62% to 0.16%), and TG (-4.95%, -11.93% to 2.04%) with no significant difference in HDLC (-0.09%, -3.10% to 2.91%). After adjusting for publication bias, ε4 carriers showed less pronounced statin effects, with smaller reductions in LDLC (mean difference: 10.04%, 6.04% to 14.04%), TC (8.99%, 5.08% to 12.90%) and TG (8.24%, 2.15% to 14.33%), along with a smaller increase in HDLC (-10.08%, -15.30% to -4.85%) compared to ε3 carriers. Study quality was unclear, and heterogeneity (partly explained by sex and Familial hypercholesterolemia) was high, especially for the percentage changes. A stronger genotype effect was seen in males. CONCLUSION: Our meta-analysis shows that APOE genotype may influence statin response, emphasizing the need to incorporate known genetic factors into personalized treatment regimens.