Introduction: High-dose statin therapy (HIST) halts coronary plaque progression and reduces the risk of cardiovascular events by increasing atheroma calcification. The Agatston score is well established in the clinical routine for the assessment of coronary artery calcification using non-contrast computed tomography. However, randomized controlled trials failed to detect an influence of HIST vs. low-to-intermediate statin therapy (LIST) on the Agatston and CAC volume score after one year. Coronary plaques with lower density including spotty calcifications may represent dynamic and early stages of atherosclerosis. We evaluated, whether CAC density differentiates in HIST- vs. LIST-treated patients after one year. 

Methods: The meta-analysis contains data from two prospective, randomized, double-blind studies (BELLES and EBEAT trial) that were designed to detect CAC changes after one year comparing HIST vs. LIST. In both studies, patient’s coronary calcification burden was measured at baseline and one-year follow-up using electron beam computed tomography (EBCT). Patients data were pooled and stratified by intensity of statin therapy. Furthermore, the cohort was divided into several subgroup analyses, accounting for LDL-Cholesterol reduction, initial Agatston score and a consistent number of lesions.

Results: Data from 852 patients, 66% female were included. The amount of CAC overall increased after 1 year [Agatston score: 169.3 (80.0, 377.1) vs. 214.9 (95.4, 450.0); p<0.0001^NP; volume score: 292.1 ± 445.4 vs. 355.5 ± 482.4; p <0.0001; number of lesions: 6 (3,10) vs. 7 (4,12); p<0.0001^NP, at baseline and follow-up, respectively]. Likewise, the average CAC density was higher at follow-up [228.8 ± 35.4 vs. 232.6 ± 37.0; p<0.0001]. HIST vs. LIST more effectively reduced LDL-cholesterol (annualized change: -58.6±50.9 vs. -44.4±43.7 mg/dL, p=0.005). Comparing patients on HIST vs. LIST, CAC density at follow-up (231.9±36.1 HU vs. 233.3±37.7, p=0.59) and its change from baseline (4.0±19.1 HU vs. 3.6±19.6 HU, p=0.73) did not differ. Subgroup analyses, stratifying by LDL-reduction (<median: 3.7±18.1 HU; ≥median: 1.7±18.5 HU, p=0.28), Agatston score at baseline (<100: 2.6±22.5 HU vs. 3.2±25.6 HU, p=0.82; ≥100: 4.8±17.0 HU vs. 3.8±16.6 HU, p=0.44, for HIST vs. LIST; respectively), and equal number of calcified lesions in both CT-scans (3.7±20.3 HU vs. 7.0±22.2 HU, p=0.24) showed similar results. 

Conclusion: HIST vs. LIST leads to a higher reduction in cholesterol levels, which does not translate into relevant differences in the change of CAC density at one-year follow-up.