Evolocumab before percutaneous coronary intervention for acute myocardial infarction: Design of the AMUNDSEN trial.

RATIONALE: PCSK9 inhibitors are currently recommended as third-line therapy for post-myocardial infarction (MI) patients, added to high-dose statin, ezetimibe, and potentially bempedoic acid when the LDL-C target of <55 mg/dL is not achieved. These guideline-driven indications result in delayed initiation of PCSK9 inhibitors, potentially missing the opportunity for benefit during the acute phase. Recent studies have demonstrated that early PCSK9 inhibition promotes anti-inflammatory effects and plaque stabilization, suggesting a potential role early in MI management.

METHODS

The AMUNDSEN trial is a randomized, international, phase IV study using a PROBE (Prospective Randomized Open, Blinded Endpoint) design to evaluate the effects of early PCSK9 inhibition in high-risk acute MI patients undergoing percutaneous coronary intervention (PCI). A total of 2,166 patients were enrolled, including those with ST-elevation MI undergoing primary PCI and those with non-ST-elevation MI with an indication for PCI, all presenting with at least 1 high-risk clinical characteristic. Patients were randomized to receive either immediate evolocumab prior to PCI alongside standard care or standard care alone. The primary objective is to achieve both a ≥ 50% reduction in LDL-C from baseline and a target LDL-C < 55 mg/dL at 12 months. The main clinical objective is to assess the composite of all-cause death or unplanned hospitalization for a cardiovascular (CV) reason at 12 months.

CURRENT STATUS: Enrollment and randomization are complete. Lipid and clinical follow-up are ongoing. Results from this study will clarify the lipid-lowering efficacy and clinical impact of early evolocumab initiation in the acute MI setting.

CONCLUSION

The AMUNDSEN trial will provide critical insights into the potential benefits of early PCSK9 inhibition in high-risk MI patients undergoing PCI.

CLINICAL TRIAL REGISTRATION: NCT (clinicaltrials.gov): 04951856 - EUCT number: 2024-518195-31-00.