Differential effects of PCSK9 inhibitors and statins on plasma ceramides in coronary artery disease.

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. Conclusion: PCSK9i is associated with significant reduction in distinct ceramide concentrations, compared statin therapy only.