Immediate Evolocumab After Heart Attack Improves LDL-C Goal Attainment but Not Early Cardiovascular Outcomes
核心洞察
The AMUNDSEN trial randomized 2,161 acute MI patients undergoing PCI to immediate evolocumab plus standard care or standard care alone.
At 12 months, 82% of evolocumab-treated patients achieved the LDL-C goal versus 40% with standard care (p<0.001).
No significant reduction in all-cause death or unplanned cardiovascular hospitalization was observed during the first year in the primary analysis.
Immediate initiation of evolocumab after a heart attack significantly improved low-density lipoprotein cholesterol (LDL-C) goal achievement, but an early reduction in all-cause death or unplanned cardiovascular hospitalisation was not observed compared with standard care. These were the main findings of the AMUNDSEN trial presented in a Hot Line session at ESC Congress 2026 and published simultaneously in JAMA.
Patients who experience a myocardial infarction (搜索) (MI) are at particularly high risk of recurrent cardiovascular events, especially within the first year. Intensive lowering of LDL-C levels is recommended after an MI in ESC Guidelines. However, as explained by Professor Gilles Montalescot, from the ACTION Study Group, Hôpital Pitié-Salpêtrière, Sorbonne University, Paris, France, the majority of patients never reach appropriate LDL-C levels after an acute MI despite the recommendations. "Only around one-third of patients achieve LDL-C targets after an acute MI," he noted. "Patients are often discharged from hospital on a high-dose statin, then ezetimibe and possibly bempedoic acid may be added, but it can take months before treatment is intensified with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, if it ever occurs."
Trial Design and Patient Population
Professor Montalescot and collaborators conducted the AMUNDSEN trial to investigate whether the PCSK9 inhibitor evolocumab, administered prior to percutaneous coronary intervention (PCI), could help more patients achieve LDL-C goals one year later and provide early clinical benefit. "There is some evidence that PCSK9 inhibitors may have so-called pleiotropic effects in the acute phase after an MI but this has not been fully evaluated in terms of early cardiovascular outcomes," commented Professor Montalescot.
AMUNDSEN was an open-label, blinded-endpoint trial conducted in 48 centres in six countries. Eligible patients had an ST-elevation MI undergoing primary PCI or a non–ST-elevation MI with an indication for PCI, both with at least one high-risk clinical characteristic. A total of 2,161 patients were randomised to immediate evolocumab prior to PCI alongside standard care or standard care alone. Patients in the control group were treated with the therapeutic options available in their country, including the use of a PCSK9 inhibitor, according to 2019 ESC guidelines. All patients had clinic visits at six weeks, six months, nine months and 12 months including LDL-C assessments. The mean age of participants was 67 years and 21% were women.
According to the ACC report, patients receiving evolocumab were given 140 mg subcutaneously every two weeks for one year, with the first injection administered prior to PCI. Standard care included high-intensity oral lipid-lowering therapy with optional PCSK9 inhibitor use per guideline indication in the control group. Nearly 60% of those enrolled had STEMI and 40% had NSTEMI.
Primary Endpoints
The primary biological objective was to achieve a reduction of at least 50% in LDL-C from baseline and a target LDL-C of less than 55 mg/dL at 12 months. The main clinical objective was to assess the composite of all-cause death or unplanned hospitalisation for a cardiovascular reason at 12 months.
A highly significant difference was observed for the primary endpoint related to LDL-C lowering: 82% of patients in the evolocumab group versus only 40% of patients in the standard-care group met the primary LDL-C endpoint at 12 months (p<0.001). Patients achieving the LDL-C target did so in nine weeks in the evolocumab group compared with 19 weeks in the standard-care group. At six weeks, median LDL-C was 16 mg/dL with evolocumab versus 56 mg/dL with standard care. "Even with five study visits and guidance to adjust lipid-lowering therapy according to ESC recommendations, attainment of LDL-C goals was low and slow in the standard-care group," commented Professor Montalescot.
Clinical Outcomes
In terms of clinical outcomes, there was no significant difference between the groups at one year. All-cause death or unplanned cardiovascular hospitalisations occurred in 14.6% of patients in the evolocumab group and 15.4% in the standard-care group in the primary intent-to-treat analysis (not significant). In a hypothesis-generating finding, Professor Montalescot noted event rates of 10.2% with evolocumab and 14.3% with standard care in a pre-specified per-protocol analysis (p=0.037).
"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," he said.
Expert Commentary and Implications
Professor Montalescot concluded: "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 added: "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."