ESC Congress 2026 Abstract · Oct 26, 2026
PCSK9i and atherosclerotic plaque regression assessed by coronary computed tomography angiography
By Sagris M, Isla LPI, Patsourakos NP et al.
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.