Early initiation of Evolocumab within 48 hours post-STEMI reduced LDL-C by 91% vs 59% and lowered 6-month MACE from 9.2% to 1.4% without safety issues.
Does early initiation of evolocumab within 48 hours of admission for acute STEMI reduce LDL-C and MACE compared to standard therapy alone?
Early initiation of evolocumab within 48 hours of STEMI admission safely and significantly reduces LDL-C and may lower the risk of MACE at 6 months.
Abstract Background Patients with STEMI remain at high risk for recurrent ischaemic events despite advances in intervention and optimal medical therapy. Despite that, many patients fail to achieve the recommended LDL-C targets within the critical early period following myocardial infarction (MI). Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) significantly reduce LDL-C and major adverse cardiovascular events (MACE) in their landmark clinical trials (1,2). However, these studies primarily enrolled patients in the chronic phase of ACS, months to years after the index event. The potential benefits and safety of initiating PCSK9i therapy in the immediate post-ACS phase remains unexplored. Purpose This investigator-initiated, prospective, randomised, open-label trial examines whether initiating Evolocumab within 48 hours of hospital admission with ACS-STEMI, on top of high-intensity statin therapy, leads to greater LDL-C reduction and improved cardiovascular outcomes compared to standard therapy alone, while also evaluating the safety of this strategy. Methods Eligible patients (aged 18-70 years) included those with STEMI and LDL-C levels exceeding 3.2 mmol/L in statin-naïve patients, more than 2.3 mmol/L in patients on low or moderate-intensity statins or more than 1.8 mmol/L if patients were on high-intensity statins. These patients were randomised in a 1:1 ratio to receive either standard guideline-directed optimal medical therapy alone (control group) or Evolocumab 140 mg every two weeks plus standard therapy (intervention group). The intervention group had the drug administered within 48 hours post-admission following successful percutaneous coronary intervention to the culprit lesion. Results Results of the interim analyses of the first 147 patients enrolled in the EARLY-STEMI trial showed a mean baseline LDL-C level of 4.17 in the Evolocumab group compared to 3.98 mmol/L in the control group. LDL-C was reduced by 6 months to 0.37 mmol/L (91% reduction) compared to 1.65 mmol/L (59% drop) in the control group (p 0.001). At the 6-month follow-up of these patients, MACE occurred in 1 patient (1.4%) in the intervention arm compared to 7 patients (9.2%) in the control group (p 0.037). No significant difference was found between both groups in terms of safety concerns. No adverse events led to drug discontinuation. Conclusion(s) Early initiation of PCSK9i therapy on top of statin therapy within 48 hours of hospital admission for STEMI resulted in a significant reduction in LDL-C at 6 months compared to statin therapy alone. Interim analysis of MACE up to 6 months of follow-up showed a lower trend in patients with PCSK9i without a concomitant increase in safety concerns. These findings highlight that PCSK9i are efficacious and safe to be introduced in the acute phase of ACS. Long-term follow-up is required to determine whether these effects are sustained. Table 1 & 2
Ali et al. (2025) studied this question. Early initiation of Evolocumab within 48 hours post-STEMI reduced LDL-C by 91% vs 59% and lowered 6-month MACE from 9.2% to 1.4% without safety issues.