SRS271 - The impact of PCSK9 inhibitors on carotid intima-media thickness and the association with lipid parameters: a systematic review, meta-analysis and meta-regression

Abstract Objective We assessed impact of PCSK9 inhibitors (PCSK9i) on carotid intima-media thickness (cIMT) and their interplay with lipid profile parameters. Methods Systematic review conducted in accordance with PRISMA guidelines. Primary endpoint was cIMT reduction (millimetres). Meta-regression examined influence of demographic, imaging, and biochemical parameters on cIMT. Heterogeneity exploration was conducted via leave-one-out and Baujat plot analyses. Results Four randomized controlled trials comparing PCSK9i plus statin versus placebo plus statin, and two single-arm studies were included, enrolling 607 patients and 2175 carotid segments. Pooled analysis demonstrated significant reduction in cIMT; mean difference (MD) −0.03 (95%c.i.: −0.05 to −0.01) (I2 = 95.4%, P < 0.01). Following exploration and mitigation of heterogeneity, this reduction persisted; MD −0.01 (95%c.i.: −0.02 to −0.01) (I2 = 0%, P = 0.59). Initially, comparison between PCSK9i and placebo yielded non-significant cIMT reduction favouring PCSK9i; MD −0.04 (95%c.i.: −0.10 to 0.03) (I² = 98.6%, P < 0.01). Following heterogeneity adjustment, effect estimate reached statistical significance, demonstrating consistent cIMT reduction with PCSK9i; MD −0.01 (95%c.i.: −0.02 to −0.01) (I² = 52%, P = 0.12). Meta-regression displayed associations between baseline cIMT (β = −0.45, P < 0.01), HDL (β = 1.92, P < 0.01) and cIMT. Pooled between-group cIMT differences showed moderate correlations with the respective differences in total (r = 0.69) and LDL cholesterol (r = 0.59). Conclusions Evidence supports potential association between PCSK9i treatment and cIMT reduction, with observed correlations involving total and LDL cholesterol indicating lipid-mediated vascular response. These findings warrant cautious interpretation given substantial heterogeneity, partly driven by baseline differences in cIMT and lipid profiles. Future studies should ensure baseline comparability in vascular and biochemical parameters to strengthen causal inferences.