Effects of residual inflammatory and cholesterol risks on cardiovascular events with evolocumab in patients with acute coronary syndrome undergoing percutaneous coronary intervention

Background Evolocumab has shown significant reductions in low-density lipoprotein cholesterol (LDL-C) levels and incident cardiovascular events among acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Nonetheless, the potential modification of evolocumab's effectiveness by baseline inflammatory risk remains unclear. We aimed to assess evolocumab's effectiveness based on baseline neutrophil-to-lymphocyte ratio (NLR) and evaluate residual inflammatory and cholesterol-related risks across varying on-treatment NLR and LDL-C levels. Methods This multicentric, retrospective analysis enrolled consecutive patients with ACS undergoing PCI and exhibiting elevated LDL-C at the First Affiliated Hospital of Zhengzhou University and Zhongda Hospital Southeast University between March 2019 and August 2021. Patients were categorized into evolocumab and standard-of-care treatment groups based on evolocumab administration. Hazard ratios for the primary composite outcome-including myocardial infarction, ischemic stroke, cardiac death, unplanned coronary revascularization, and hospitalization due to unstable angina-comparing baseline NLR quartiles were computed using multivariable Cox regression. We assessed evolocumab's impact on the primary outcome across median-based NLR dichotomization and evaluated the outcome across 1-month NLR and LDL-C levels. Results The median baseline NLR was 2.99 (IQR: 2.14-4.69), remaining stable following evolocumab therapy. Each NLR quartile increase heightened the risk of primary outcome by 29% (95% CI, 17-42%; P < 0.01). The relative risk reductions with evolocumab were consistent across NLR categories (P-interaction > 0.05), but absolute risk reductions were higher in high-NLR patients (2.9% vs. 6.2%). Residual inflammatory and cholesterol risks, indicated by on-treatment NLR and LDL-C, independently correlated with the primary outcome (P < 0.001). Conclusions Higher baseline NLR is associated with increased cardiovascular risk in ACS/PCI patients. Relative risk reductions with evolocumab were consistent across NLR categories, while absolute risk reductions were more significant in high-NLR patients. Minimized risk is observed in patients with the lowest on-treatment NLR and LDL-C levels.