Indirect comparison of statin–ezetimibe and statin–PCSK9 inhibitor combination therapies for coronary artery plaque regression in acute coronary syndrome

Previous studies have shown that intensive LDL cholesterol (LDL-C)–lowering therapy using additional agents such as ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) alongside statin monotherapy reduces coronary artery plaque volume in patients with acute coronary syndrome (ACS).1–3 However, few studies have compared statin plus PCSK9i therapy with statin plus ezetimibe therapy. Therefore, we conducted a systematic review and meta-analysis to compare the efficacy of these combination therapies on plaque atheroma volume. Studies were eligible if they met the following criteria: (i) the study was published in peer-reviewed journals; (ii) the study evaluated plaque characteristics using intravascular ultrasound (IVUS) before and after LDL-C-lowering therapy with statin monotherapy, statin plus ezetimibe, and statin plus PCSK9i; and (iii) the study included patients with ACS. We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for studies published from database inception to April 2025. The primary outcome was the change in per cent atheroma volume (PAV) measured by IVUS before and after LDL-C-lowering therapy.