Initiating the PCSK9* inhibitor evolocumab in the cath lab prior to PCI** in patients with acute myocardial infarction (MI) dramatically lowers LDL-C compared with standard care in the phase IV AMUNDSEN trial presented at ESC 2026.
Eighty-two percent of patients reached the guideline-recommended LDL-C target of <55 mg/dL at 1 year vs 40 percent among those treated with standard care, according to study author Professor Gilles Montalescot, a cardiologist at Pitié-Salpêtrière Hospital in Paris, France. [JAMA 2026:doi:10.1001/jama.2026.17302]
He explained that despite the currently recommended stepwise treatment approach, which allows PCSK9 inhibition after oral therapy, most patients cannot reach the guideline-recommended LDL-C target. “Only 1 in 3 achieve LDL-C targets after an acute MI. 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 PCSK9 inhibitors, if it ever occurs.”
“Reaching the guideline-recommended LDL-C target is possible with more aggressive strategies, such as evolocumab on the first day,” he added. In AMUNDSEN, starting evolocumab promptly in hospital significantly reduced LDL-C. However, the fact that 20 percent of patients did not meet their targets emphasized the importance of developing aggressive preventive strategies and implementing them early for high-risk patients, said Montalescot.
The trial was conducted at 48 sites across six countries and enrolled 2,161 adults (mean age 67 years, 79 percent male). All were at least 55 years old and had either a STEMI (58 percent) or an invasively managed NSTEMI with at least one additional high-risk feature (42 percent). They were randomly assigned to receive evolocumab 140 mg subcutaneously every 2 weeks for 1 year, with the first injection given before PCI, on top of standard care, or to receive standard care alone.
No difference in all-cause death, CV hospitalization
Although LDL-C levels decreased, early PCSK9 inhibition showed no clinical benefit or LDL-independent pleiotropic effects after 1 year.
All-cause death or unplanned CV hospitalization did not differ significantly between the evolocumab and standard-care groups (14.6 percent vs 15.4 percent; adjusted odds ratio [aOR], 0.94, 95 percent confidence interval [CI], 0.73-1.19).
“On top of high-dose statins, we do not observe clinically meaningful pleiotropic effects during the first few months or the first year of treatment,” Montalescot said.
Dr Robert Giugliano of Brigham and Women’s Hospital in Boston, Massachusetts, US, who was not involved in the trial, commented that the 1-year follow-up may explain why the trial showed no difference in clinical outcomes.
“I think the main contributor was that the trial simply didn’t run long enough,” he said. “If you lower somebody’s cholesterol today, you’re unlikely to prevent their death tomorrow, probably not even next week or the next month. It likely takes at least a year, if not longer.”
Nonetheless, Giugliano said achieving a median LDL-C of 16 mg/dL in patients is “truly groundbreaking—a terrific result.”
Benefits a marathon, not a sprint
In a related editorial, Dr Kausik Kumar Ray and Dr Christophe Stevens of Imperial College London, UK, said that the AMUNDSEN trial ultimately shows that in patients with MI, “the benefits of LDL-C lowering are a marathon, not a sprint, and that rapid LDL-C reduction at 7 days with a PCSK9 monoclonal antibody will take years to translate into meaningful clinical benefits.” [JAMA 2026; doi:10.1001/jama.2026.16837]
They suggested that rather than further lowering LDL-C in those with CVD, a better approach might be to “begin earlier” with modest reductions in those without evident disease. “Achieving that goal may signal the start of the end for atherosclerotic CVD,” they said.