Lipid lowering after acute myocardial infarction (MI) is central to secondary prevention, but stepwise therapy may delay LDL-C target attainment. The AMUNDSEN trial, presented at ESC Congress 2026 and simultaneously published in JAMA, assessed whether pre-PCI evolocumab could accelerate LDL-C reduction and improve clinical outcomes.¹

The trial enrolled 2,161 high-risk STEMI/non-STEMI patients undergoing primary or urgent PCI across 48 sites in six countries. Patients received evolocumab 140 mg every two weeks for one year, starting before PCI, plus standard care, or standard care alone. Both groups received high-intensity lipid-lowering therapy; PCSK9 inhibitors were permitted in controls.

At six weeks, median LDL-C was 16 vs. 56 mg/dL with evolocumab vs. standard care. At 12 months, 82% vs. 40% achieved LDL-C <55 mg/dL with ≥50% reduction from baseline (adjusted odds ratio [OR], 5.54; 95% CI, 4.50-6.82; p<0.001). Despite better lipid control, one-year clinical outcomes were similar: 14.6% vs. 15.4% for all-cause death or unplanned cardiovascular hospitalization (adjusted OR, 0.94; 95% CI, 0.73-1.19; p=0.59). Serious adverse events were comparable.

AMUNDSEN in Clinical Context

Contemporary European guidance recommends an LDL-C target of <55 mg/dL in very-high-risk patients and supports early combination lipid-lowering therapy during the index hospitalization for acute coronary syndrome.^2,3 AMUNDSEN highlights the importance of timing: Pre-PCI evolocumab accelerated and sustained LDL-C target attainment but did not improve one-year clinical outcomes.

Clinical Perspective

AMUNDSEN should not be viewed as evidence against intensive lipid lowering; rather, it distinguishes rapid LDL-C target attainment from short-term clinical benefit. Early PCSK9 inhibition may benefit selected high-risk patients, particularly those with markedly elevated baseline LDL-C or anticipated challenges with follow-up; however, routine pre-PCI use to reduce short-term events remains unproven. The EVOLVE-MI trial (NCT05284747), enrolling 6,019 patients, should provide further evidence on whether very early evolocumab therapy translates into long-term cardiovascular benefit.

Bottom Line

AMUNDSEN demonstrates that upstream pre-PCI evolocumab rapidly achieves LDL-C targets after acute MI but this does not translate into improved one-year clinical outcomes. Whether earlier, sustained LDL-C reduction can deliver greater cardiovascular benefit with longer follow-up remains an important unanswered question.

References

1. Montalescot G, Ferrari E, Souteyrand G, et al. LDL cholesterol lowering with evolocumab before percutaneous coronary intervention for acute myocardial infarction: the AMUNDSEN randomized clinical trial. JAMA. Published online August 29, 2026. doi:10.1001/jama.2026.17302
2. Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44(38):3720-3826. doi:10.1093/eurheartj/ehad191
3. Mach F, Koskinas KC, Roeters van Lennep JE, et al. 2025 Focused update of the 2019 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2025;46(42):4359-4378. doi:10.1093/eurheartj/ehaf190