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.