First-line evolocumab combined with high-intensity lipid-lowering therapy produced rapid and sustained LDL-C reduction in patients with acute MI undergoing PCI, with more than 80% reaching the guideline recommended target of LDL-C less than 55 mg/dL at one year, said researchers presenting findings from the AMUNDSEN trial at ESC Congress 2026. However, no clinical benefit was detected during the first year of follow-up.

The trial, which was also published in JAMA, randomized 2,161 patients (mean age, 67 years; 79% male) at 46 sites in six countries to receive evolocumab (140 mg subcutaneously every two weeks for one year) plus standard care or standard care alone. Standard care included high-intensity oral lipid-lowering therapy with optional PCSK9 inhibitor use per guideline indication in the control group. For those receiving evolocumab, the first injection was prior to PCI. Nearly 60% of those enrolled in the study had STEMI and 40% had NSTEMI.

The primary outcome of LDL-C less than 55 mg/dL and at least 50% reduction in LDL-C from baseline at 12 months was achieved in 82% of patients in the evolocumab group compared with 40% of those in the standard care group. At six weeks, median LDL-C was 16 mg/dL with evolocumab vs. 56 mg/dL with standard care.

However, researchers said no clinical benefit was detected during the first year of follow-up with evolocumab compared with placebo. The main clinical endpoint of all-cause death or unplanned cardiovascular hospitalization at 12 months occurred in approximately 15% of patients in both groups.

“The lack of a clear effect on cardiovascular outcomes in the primary analysis suggests evolocumab may not have early clinically meaningful pleiotropic effects and the benefit of lipid lowering may require more time,” said Gilles Montalescot, MD, from the ACTION Study Group. “Immediate in-hospital initiation of evolocumab substantially improved LDL-C goal attainment but even then, 1 in 5 patients failed to reach their target a year later. Developing additional preventive strategies and delivering them early remains an imperative for high-risk patients.”

In a related editorial comment, Kausik Kumar Ray, MD, FACC, and Christophe A.T. Stevens, PhD, said the trial “shows that for patients with MI, the benefits from LDL-C lowering are a marathon, not a sprint, and that a rapid LDL-C reduction at 7 days with a PCSK9 monoclonal antibody will take years to translate into meaningful clinical benefits.” They add: “If the aim is to reduce the burden of cardiovascular disease globally, the smart move may not be to only go lower with respect to LDL-C in those with cardiovascular disease, but to also begin earlier, even with modest LDL-C lowering, in those without clinically manifest disease. Achieving that goal may well signal the beginning of the end for atherosclerotic cardiovascular diseases.”

Visit ACC’s ESC Congress 2026 coverage page to explore the latest science and key takeaways shaping cardiovascular care.

Clinical Topics: Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Lipid Metabolism, Novel Agents

Keywords: ESC Congress, ESC26, Myocardial Infarction, Percutaneous Coronary Intervention, Antibodies, Monoclonal, Proprotein Convertase 9