PCSK9i and atherosclerotic plaque regression assessed by coronary computed tomography angiography

Background Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) provide profound lipid lowering beyond standard therapy. However, their impact on coronary plaque characteristics, assessed by coronary computed tomography angiography (CCTA), remains incompletely defined. Methods Five studies comprising 256 patients who underwent serial CCTA imaging met the predefined inclusion criteria. The mean age was 61.2 ± 8.3 years, 62% were male, and the median follow-up was 14.6 months. Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated for biochemical and CCTA-derived parameters using random-effects models. Results PCSK9i therapy was associated with significant reductions in total cholesterol (SMD: −1.81; 95% CI: −2.88 to −0.75; I²=96%), LDL-C (SMD: −2.32; 95% CI: −3.38 to −1.26; I²=96%), lipoprotein(a) (SMD: −0.49; 95% CI: −0.73 to −0.25; I²=49%), and triglycerides (SMD: −0.35; 95% CI: −0.52 to −0.19; I²=10%), with a modest increase in HDL-C (SMD: 0.16; 95% CI: −0.00 to 0.33; I²=7%). C-reactive protein also showed a slight reduction. On CCTA, non-calcified plaque volume was significantly reduced (SMD: −0.17; 95% CI: −0.36 to −0.02; I²=0%), while the Agatston score significantly increased (SMD: 0.32; 95% CI: 0.09 to 0.55; I²=0%). Reductions were also noted for total plaque volumes (SMD: -0.12, 95% CI: -0.72 to 0.48; I2=88%), fibrous plaque (SMD: -0.28, 95% CI: -0.89 to 0.33; I2=73%), necrotic plaque (SMD: -0.34, 95% CI: -1.01 to 0.33; I2=90%) and increase in calcified plaque volume (SMD: 0.13, 95% CI: -0.16 to 0.42; I2=49%), however without reaching statistical significance. Notably, most patients (78.8%) were already receiving high-intensity statins and ezetimibe prior to PCSK9i initiation. Conclusion PCSK9i therapy is associated with significant lipid reduction and favorable modulation of coronary plaque composition, characterized by regression of non-calcified plaque and increased calcification-delipidisation, suggesting plaque stabilization. These findings support the complementary role of PCSK9i beyond statins and highlight CCTA as a unique, non-invasive tool for monitoring plaque burden and therapeutic response.