Acute-phase Lipid-lowering Effects of Evolocumab in Patients with AMI; Pre-specified Secondary Analysis of the EVO-STEMI Trial

초록

Background: Intensive lowering of low-density lipoprotein cholesterol (LDL-C) reduces coronary plaque volume and lipid content, increases fibrous cap thickness, and helps prevent plaque rupture. Current guidelines recommend early initiation of high- intensity statins in patients with ST-segment elevation myocardial infarction (STEMI) to prevent recurrent events. However, achieving LDL-C targets early after STEMI is often difficult with statin therapy alone, highlighting the need for additional lipid-lowering agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. This pre-specified secondary analysis of EVO-STEMI trial (NCT06081803) evaluated the effects of early evolocumab administration on atherogenic lipid profiles and safety in the setting of acute MI. Study Methods: Between December 2020 and December 2024, 166 patients (mean age, 59 years) with STEMI were randomized in a 2:1 ratio to receive a fixed-dose combination of rosuvastatin 10 mg and ezetimibe 10 mg, with or without a single subcutaneous injection of evolocumab 420 mg administered before primary percutaneous coronary intervention (PCI). Changes in lipid profiles, including lipoprotein(a) (Lp (a)), and safety outcomes were assessed at 4 weeks after PCI. Results: Of the 110 patients assigned to evolocumab, 109 (99%) received the injection. There was no cross-over in either group. In the intention-to-treat analysis, adjunctive evolocumab significantly reduced LDL-C compared with standard care (70.9% [117.9 to 32.6 mg/dL] vs 46.2% [115.4 to 57.2 mg/dL]; mean difference 24.7%, 95% confidence interval [CI] 17.3 to 32.1; p<0.0001). The increase in Lp (a) levels over 4 weeks was significantly attenuated in the evolocumab group compared with the standard care group (12.4% (32.7 to 40.9 mg/dL) vs 38.1% (36.1 to 51.6 mg/dL); mean difference 25.8%, 95% CI 5.4 to 46.1 %; p=0.013). The proportion of patients achieving an LDL-C level <55 mg/dL was significantly higher in the evolocumab group than in the standard care group (90.9% vs 58.9%; p<0.0001). At 4 weeks, the overall incidence of adverse events was lower in the evolocumab group than in the standard care group, and the frequency of serious adverse events did not differ significantly between the two groups (4.6% vs 8.9%, p=0.310). Conclusions: In patients with STEMI undergoing primary PCI, preemptive administration of evolocumab in addition to moderate-intensity statin and ezetimibe before lipid levels are known resulted in greater LDL-C reduction, attenuation of the acute rise in Lp (a), and a favorable short-term safety profile compared with statin and ezetimibe alone.