Early Evolocumab before PCI Achieves LDL-C Targets After Acute MI, but No Short-Term Clinical Benefit: JAMA
France: Researchers have found in a new study that among patients with acute myocardial infarction undergoing PCI, early in-catheterization laboratory initiation of evolocumab plus high-intensity lipid-lowering therapy produced rapid and sustained LDL-C reduction, with more than 80% achieving guideline-recommended LDL-C targets at 1 year. However, no additional clinical benefit was observed during the first year, suggesting that PCSK9 inhibitors may not provide meaningful acute pleiotropic effects beyond standard care.
The findings are from the AMUNDSEN randomized clinical trial, published in JAMA, by Gilles Montalescot of Sorbonne Université, INSERM UMRS1166, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France, and colleagues.
PCSK9 inhibitors are generally introduced after myocardial infarction when LDL-C remains above recommended levels despite conventional lipid-lowering therapy. The researchers investigated whether administering evolocumab immediately, before mechanical reperfusion, could help patients achieve lipid targets more effectively than the conventional stepwise approach.
The international phase 4 trial included 2161 adults with high-risk acute MI across 48 sites in six countries. Participants had either high-risk STEMI or NSTEMI with additional risk characteristics. Enrollment took place between September 2021 and May 2025, with follow-up completed in May 2026.
Patients were randomly assigned to receive either evolocumab 140 mg every 2 weeks for one year, with the first dose administered before PCI, alongside standard high-intensity lipid-lowering therapy, or standard care alone. In the standard-care group, PCSK9 inhibitor treatment could be added later when indicated by guidelines.
The primary outcome was achieving an LDL-C level below 55 mg/dL together with at least a 50% reduction from baseline at 12 months.
- The LDL-C target was achieved by 82% of patients receiving early evolocumab, compared with 40% receiving standard care.
- Early evolocumab was associated with significantly higher odds of achieving the target, with an adjusted odds ratio of 5.54.
- LDL-C reduction occurred rapidly; at six weeks, median LDL-C was 16 mg/dL with evolocumab versus 56 mg/dL with standard care.
- Despite the marked LDL-C reduction, the main clinical outcome of all-cause death or unplanned cardiovascular hospitalization did not differ significantly between groups.
- This outcome occurred in 14.6% of patients receiving evolocumab versus 15.4% receiving standard care (adjusted OR, 0.94).
- Only 3.8% of patients in the standard-care group ultimately received a PCSK9 inhibitor, highlighting ongoing barriers related to prescribing, access, and availability.
The study had limitations, including its open-label design and differences in background care across countries. Although LDL-C outcomes were objectively measured and clinical events were independently adjudicated, the per-protocol analysis may have been affected by selection bias.
Overall, early evolocumab during catheterization rapidly improved LDL-C target attainment, but did not reduce death or unplanned cardiovascular hospitalization within one year. Longer follow-up is needed to determine whether the early, substantial LDL-C reduction provides later cardiovascular benefits.
Reference:
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
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