Evolocumab early reduces IL-1β/IL-17A and improves left ventricular function in STEMI: an observational study in the...

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 ST-segment elevation myocardial infarction (STEMI), the anti-inflammatory effects and impact on early cardiac remodeling of PCSK9i remain unclear. This study investigated the effects of PCSK9i on early inflammatory factors [interleukin (IL)- 1β, IL-18, IL-17A, and C-C chemokine receptor 2 (CCR2)] and left ventricular (LV) function in STEMI patients.

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). All patients were observed for 12 weeks.

At 4 weeks, the evolocumab group exhibited a greater reduction in IL-1β compared to statin alone (-29.35% vs -25.27%, P = 0.012). Similarly, IL-17A decreased more significantly with evolocumab than with statin therapy (-30.22% vs -25.35%, P = 0.023). By 12 weeks, evolocumab significantly improved left ventricular ejection fraction (LVEF) 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, reductions in IL-1β and IL-17A at 4 weeks as independent predictors of ΔEF≥ 5% at 12 weeks. Mediation analysis showed that 8.74% and 9.60% of LV functional improvement were attributable to reductions in IL-1β and IL-17A respectively.

Our findings support evolocumab's role beyond lipid-lowering, suggesting that early PCSK9i as a potential strategy to mitigate early inflammation-driven cardiac dysfunction in STEMI management.