ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Cardiovascular and Smooth Muscle Pharmacology
Differential Effects of PCSK9 Inhibitors and Statins on Plasma Ceramides in Coronary Artery Disease
Provisionally accepted
- Beijing Anzhen Hospital, Capital Medical University, Chaoyang District, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
BACKGROUND While elevated plasma ceramides are independently associated with increased cardiovascular risk in patients with coronary artery disease (CAD), the impact of current lipid-modifying drugs on ceramides, remains under-researched. This study examines the effect of PCSK9 inhibitors on plasma ceramides in patients with CAD who had received statin therapy. METHODS Comparing the effect of PCSK9i vs statin on ceramide levels. The primary outcome was percent change in ceramide levels. Subgroup analyses were done to explore potential treatment effect differences. RESULTS Among 292 patients (44% statin group, 56% PCSK9i group), baseline characteristics were broadly similar. PCSK9i use significantly reduced ceramide levels compared to statin therapy: Cer 16:0 decreased by −22.93% (95% CI, −29.73% to −16.14%), Cer 18:0 by −24.54% (95% CI, −33.07 to −16.01), and Cer 24:0 by −34.82% (95% CI, −48.41 to −21.23). PCSK9i also significantly lowered LDL-C by 29.63%, triglycerides by 16.69%, and total cholesterol by 10.25%, while modestly increasing HDL-C. Sensitivity and subgroup analyses confirmed the consistent ceramide-lowering effect of PCSK9i across various patient demographics and baseline characteristics. CONCLUSIONS PCSK9i is associated with significant reduction in distinct ceramide concentrations, compared statin therapy only.
Keywords: PCSK9 inhibitors, statin, ceramide, Coronary Artery Disease, Lipid
Received: 17 Oct 2025; Accepted: 03 Dec 2025.
Copyright: © 2025 Zhang, Ding and Zeng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yong Zeng
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.