Comparing coronary artery plaque regression in patients treated with ezetimibe or PCSK9 inhibitors following acute coronary syndrome: a systematic review and meta-analysis

Background Lipid-lowering therapy (LLT) is crucial to treat atherosclerotic diseases. Randomized controlled trials (RCTs) have shown further plaque regression by adding ezetimibe or proprotein convertase subtilisin kexin type-9 inhibitor (PCSK9i) over statin monotherapy in patients with acute coronary syndrome (ACS). However, it remains unclear if PCSK9i therapy shows superior results compared with ezetimibe therapy. Methods PubMed, EMBASE, and Cochrane CENTRAL databases were searched in November 2024. Randomized controlled trials (RCTs) investigating intensive LLT (statin plus ezetimibe or PCSK9i) were included. The endpoint was percent atheroma volume (PAV). Meta-analysis and meta-regression analysis were performed. Results Five studies with 1,001 imaging subjects were included. These trials compared statin monotherapy versus statin plus ezetimibe therapy or statin plus PCSK9i therapy. Statin monotherapy, statin plus ezetimibe therapy, and statin plus PCSK9i therapy were associated with pooled PAV decreases of 0.98% (95% CI: 0.40, 1.57, I2=92%), 2.06% (95% CI: 1.35, 2.78, I2=25%), and 2.14% (95% CI: 1.34, 2.94, I2=79%), respectively (Figure 1A). There were no significant subgroup differences between statin plus ezetimibe therapy versus statin plus PCSK9i therapy (p=0.89). Meta-regression analysis revealed a significant association between follow-up low-density lipoprotein cholesterol levels and PAV change (p=0.01) (Figure 1B). Conclusions No significant differences were observed for plaque regression between intensive LLT with ezetimibe or PCSK9i. Further studies are warranted to compare the two contemporary strategies.Figure 1A Figure 1B