Evolocumab early reduces Interleukin-1β/Interleukin-17A and improves left ventricular function in ST-segment elevation myocardial infarction: an observational study in the real world
J Gao, M L Zhang, J Y Liu, A R Jing, J F Zhang, C P Li, Z Cui, Y LiuAbstract
Background
While proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) effectively lower low-density lipoprotein cholesterol (LDL-C) levels and reduce the incidence of major adverse cardiovascular events (MACE) in patients with STEMI, the anti-inflammatory effects and impact on early cardiac remodeling of PCSK9i remain unclear.
Purpose
This study aims to investigate the effects of PCSK9i on early inflammatory factors[interleukin (IL)-1β , IL-18, IL-17A, and CC chemokine receptor 2 (CCR2)] and left ventricular (LV) function in ST-elevation-myocardial infarction(STEMI) patients.
Methods
Totally 257 STEMI participants were divided into 2 groups based on their real-world prescriptions: those treated with statin only (statin group) and those treated with statin in addition to the evolocumab (evolocumab group). Serum levels of IL-1β , IL-18, IL-17A, and CCR2 were measured by enzyme-linked immunosorbent assay at baseline, 1 week, and 4 weeks. LV function was assessed by echocardiography at baseline, 4 weeks and 12 weeks.
Results
At 4 weeks, the evolocumab group exhibited a greater reduction in IL-1β (−29.35% ± 12.08%, from 16.95 to 11.96mmol/L) compared to statin alone (-25.27% ± 10.89%, from 16.64 to 12.48 mmol/L), with a mean between-group difference of -4.08% (95% CI: -7.24% to -0.91%, p= 0.012). Similarly, IL-17A decreased more significantly with evolocumab (-30.22% ± 15.91%, from 5.64 to 3.88 mmol/L) than with statin therapy (-25.35% ± 15.91%, from 5.73 to 4.21 mmol/L), with a mean between-group difference of -4.88% (95% CI: -9.06% to -0.69%, p = 0.023). By 12 weeks, evolocumab significantly improved LV ejection fraction (7.53% ± 7.44% vs 5.07% ± 8.05%, p=0.007) , especially in the patients with LVEF<50% at baseline (11.36% vs. 7.40%, p = 0.014) and increased the incidence of LV global function improvement (ΔEF≥ 5%: 78.2% vs 55.1%, p<0.001) compared to statin alone. Multivariate analysis identified the use of evolocumab (OR= 4.36, 95% CI = 1.16-16.23, p=0.029), reductions in IL-1β (OR= 1.49, 95% CI= 1.10-2.02, p=0.011) and IL-17A (OR= 1.47, 95% CI =1.02-2.11, p=0.037) at 4 weeks as independent predictors of ΔEF≥ 5% at 12 weeks adjusted for the change in LDL-C. Mediation analysis showed that 8.74% and 9.60% of LV functional improvement were attributable to reductions in IL-1β and IL-17A respectively.
Conclusions
Early evolocumab therapy in STEMI rapidly attenuates inflammation and improves left ventricular function, with partially mediated by IL-1β/IL-17A axis. Our findings support evolocumab's role beyond lipid-lowering, suggesting that early PCSK9 inhibition as a potential strategy to mitigate early inflammation-driven cardiac dysfunction in STEMI management.