Differential Effects of PCSK9 Inhibitors and Statins on Plasma Ceramides in Coronary Artery Disease

Patients diagnosed with CAD who underwent at least two plasma ceramide examinations at Beijing Anzhen Hospital, Capital Medical University, were screened between March 2023 and May 2025 (Patients with multivessel coronary artery disease undergo staged treatment of the affected vessels, with interventions spaced approximately one month apart). Exclusion criteria included: (1) patients previously treated with PCSK9i before enrollment; (2) patients with a time interval between serial ceramide measurements of less than 3 weeks or more than 6 weeks; (3) patients with incomplete clinical data regarding lipid-lowering treatment protocols. Study participants were categorized based on the initiation of PCSK9i therapy after the first ceramide examination (Treatment group: PCSK9i combined with statin, Placebo group: statin only or combined with ezetimibe). The primary efficacy endpoint was the percentage change in plasma ceramide from baseline to repeated measurement in the PCSK9i group compared with the placebo group. Baseline was defined as the last measurement prior to the first dose of PCSK9i. The study protocol was in accordance with the Declaration of Helsinki and was approved by the Medical Ethics Committee of Beijing Anzhen Hospital (IRB number: KS2023081), with informed consent obtained from all participants.