Effects of high- versus low-intensity lipid-lowering treatment in patients undergoing serial coronary computed tomography angiography: results of the multi-center LOCATE study

Aim: To evaluate the effects of lipid-lowering medications of different intensities on total, calcified, and non-calcified plaque volumes in patients undergoing serial cardiac computed tomography angiography (CCTA). Methods: Individuals with chronic coronary syndromes from 11 centers were included in a retrospective registry. Total, calcified, and non-calcified plaque volumes were quantified and the relative difference in plaque volumes between baseline and follow-up CCTA was calculated. The intensity of lipid-lowering treatment was designated as low, moderate, or high, based on current recommendations. Results: Of 216 patients (mean age 63.1 ± 9.7 years), undergoing serial CCTA (median timespan = 824.5 [IQR = 463.0–1323.0] days), 89 (41.2%) received no or low-intensity lipid-lowering medications, and 80 (37.0%) and 47 (21.8%) moderate- and high-intensity lipid-lowering agents, respectively. Progression of total and non-calcified plaque was attenuated in patients on moderate-/high- versus those on no/low-intensity treatment and arrested in patients treated with high-intensity statins or PCSK9 inhibitors (p < 0.001). Halted increase of non-calcified plaque was associated with LDL-cholesterol reduction (p < 0.001), whereas calcified plaque mass and Agatston score increased irrespective of the lipid-lowering treatment (p = NS). The intensity of lipid-lowering therapy robustly predicted attenuation of non-calcified plaque progression as a function of the time duration between the two CCTA scans, and this was independent of age and cardiovascular risk factors (HR = 3.83, 95% CI = 1.81–8.05, p < 0.001). Conclusion: The LOCATE multi-center observational study shows that progression of non-calcified plaques, which have been previously described as precursors of acute coronary syndromes, can be attenuated with moderate-intensity, and arrested with high-intensity lipid-lowering therapy. German clinical trials register: DRKS00031954. Graphical abstract: High-intensity lipid-lowering agents, including potent statins and PCSK9 inhibitors induce intense LDL-cholesterol reduction and arrest of non-calcified plaque. (Figure presented.) © Springer-Verlag GmbH Germany, part of Springer Nature 2024.