Plaque regression and stabilization by proprotein convertase subtilisin/kexin type 9 inhibitors: a meta-analysis of intravascular imaging studies

BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are potent lipid-lowering agents that may also influence the structural and compositional features of coronary atherosclerotic plaques. Although individual intravascular imaging modalities have demonstrated beneficial effects, an integrated evaluation across modalities remains limited. METHODS: We performed a systematic review and meta-analysis of studies evaluating the impact of PCSK9 inhibitors on coronary plaque using intravascular ultrasound, near-infrared spectroscopy, and optical coherence tomography. PubMed, Web of Science, and the Cochrane Library were searched up to June 2025. The primary outcomes were changes in percent atheroma volume (PAV), fibrous cap thickness (FCT), and maximum lipid core burden index within 4 mm (maxLCBI4 mm). A random-effects model was used to pool results. RESULTS: Ten studies with a total of 1642 patients (PCSK9 inhibitor group: 816; control group: 826) were included. PCSK9 inhibitors significantly reduced PAV compared with control [mean difference: -1.03%; 95% confidence interval (CI): -1.46 to -0.60; P < 0.00001; I2 = 27%]. Minimum FCT showed an increase (mean difference: 28.44 μm; 95% CI: 6.10-50.77; P = 0.01; I2 = 82%). Furthermore, PCSK9 inhibitors reduced maxLCBI4 mm (mean difference: -39.73; 95% CI: -65.49 to -13.98; P = 0.002). CONCLUSION: This comprehensive intravascular imaging meta-analysis demonstrates that PCSK9 inhibitors are associated with both regression and stabilization of coronary plaques, as evidenced by reductions in PAV and lipid content and increases in fibrous cap thickness. These imaging-based structural changes may underlie the cardiovascular benefits observed in major outcome trials.