Background: Lipid-lowering medications can reduce atherosclerotic plaque burden and improve outcomes in patients with coronary artery disease (CAD). Although high-intensity lipid-lowering agents may be advantageous compared to low-intensity agents, multi-center data are lacking. Coronary computed tomography angiography (CCTA) provides the non-invasive and quantitative assessment of plaque burden and composition. 

Aim: To evaluate the effect of high- versus low-intensity lipid-lowering treatment on morphological coronary plaque characteristics in patients with suspected or known CAD, who underwent serial, two clinically indicated coronary computed tomography angiography (CCTA) scans.

Methods: Between October 2006 and February 2023, patients with no or unchanged lipid-lowering treatment from 11 imaging centers who underwent at least 2 CCTA scans (median delta time between CCTA scans 26.2 (15.0-42.2) months) were analyzed. Quantitative measurements of the total, calcified, and non-calcified plaque volumes were performed serially and the relative differences in plaque volume between the follow-up and baseline scans were calculated. The intensity of lipid-lowering treatment was judged as low or moderate/high intensity based on current recommendations.

Results: A total of 188 patients were included; 63.3±9.8 years old, 50(26.6%) female and 25 (13.3%) had diabetes mellitus. Baseline median GFR was 84.3 (71.0 - 94.0) ml/min/1.73², median C-reactive protein (CRP) was 1.3 (0.3 - 2.9) mg/dl and total, HDL and LDL cholesterol, were 182.0 (142.0 - 217.0), 49.0 (42.0 - 59.0) and 103.0 (71.0-139.5) mg/dl, respectively. After the baseline CCTA scan no/low versus moderate/high intensity lipid-lowering treatment was initiated in 83 versus 105 patients, which was kept until the 2nd CCTA scan. Fifteen (8,0%) patients of the high-intensity regime received PCSK9 inhibitors. Moderate/high intensity treatment significantly attenuated the progression of total plaque burden [8.3 (-0.8 to 19.2) % versus 14.8 (2.6 to 32.8) %, p=0.01], whereas it stopped progression of the non-calcified plaque burden [0.8 (-13.5 to 13.8) % versus 8.9 (-3.6 to 33.5) %, p<0.001]. Calcified plaque burden, on the other hand, was not significantly affected by the intensity of the lipid-lowering treatment [11.5 (1.3 - 31.7) % versus 21.4 (2.6 - 46.3) %, p=0.07]. Multivariate regression analysis identified the intensity of lipid-lowering therapy as a predictor of attenuated non-calcified plaque progression (p=0.04), independent of age and cardiovascular risk factors. 

Conclusion: Moderate/high-intensity lipid-lowering treatment can efficiently attenuate total and non-calcified plaque burden progression over time in patients with CAD and this can effectively be monitored non-invasively using serial CCTA. Since non-calcified plaques have been previously described as precursors of plaque rupture, resulting in acute coronary syndromes, this finding may provide a potential pathophysiologic link between intense pharmacologic therapy and improved cardiac outcomes.