High-intensity lipid-lowering therapy accelerates early plaque regression: a FLOWPROMOTE sub study

Abstract Background Previous studies, primarily using intravascular ultrasound (IVUS), have demonstrated that coronary plaque regression is achievable, particularly with lipid-lowering therapies (LLT). However, the rate at which plaque regression occurs after LLT initiation remains unknown. Coronary computed tomography angiography (CCTA) enables precise quantification of atherosclerotic plaque composition and burden, facilitating assessment of early plaque regression to optimize coronary artery disease (CAD) management. Objective The aim of this study was to compare early (0-9 months) versus later (9-18 months) coronary plaque regression in patients with stable CAD following initiation of usual care versus intensive care LLT. Methods This multicenter, randomized controlled trial included 104 statin-naïve patients with stable obstructive CAD identified on CCTA. Patients were randomized 1:1 to either usual care LLT (UC-LLT, 40 mg atorvastatin daily) or intensive care LLT (IC-LLT, 40 mg rosuvastatin plus 10 mg ezetimibe daily) for 18 months with repeat CCTA scans at 9- and 18-months follow-up. Coronary plaque quantification was performed in a blinded manner using a semi-automated plaque analysis software (AutoPlaque v. 2.9). Total plaque (TP), non-calcified plaque (NCP), calcified plaque (CP), and low-density non-calcified plaque (LD-NCP) were quantified and expressed in volumes. Results Overall, a significant reduction was observed in TP, NCP, and LD-NCP volumes in both time intervals, while CP volumes increased significantly in both time intervals (Table 1). In the IC-LLT group, significantly greater reduction in TP, NCP, and LD-NCP volumes were observed within the first 9 months compared to the subsequent time period. No between-period differences in plaque volumes were observed in the UC-LLT group. Of the total change in plaque volumes, a greater proportion of NCP volume reduction occurred in the IC-LLT than in the UC-LLT group within the first 9 months, 65% versus 40% (P=0.018) (Figure 1A). When comparing the relative plaque changes between groups, the IC-LLT exhibited significantly greater reductions in NCP and LD-NCP volumes within the first 9 months compared to the UC-LLT group, while no between-group differences were observed between 9 and 18 months (Figure 1B). Conclusion Intensive versus usual care LLT is associated with more profound and accelerated plaque regression during the first 9 months of treatment. Large-scale prospective studies with clinical event-driven endpoints are needed to determine the prognostic significance of early plaque modification.