Acute Myocardial Infarction Upbound to PCI Immediately (STEMI) or in the Next Three Days (NSTEMI), and Randomized to Subcutaneous Evolocumab or Normal Strategies to Reach Guidelines LDL Objectives in the Real-world

doi:10.1001/jama.2026.17302

AMUNDSEN

Patient / Population Intervention / Exposure Comparison Outcome

In 2,161 patients with acute myocardial infarction undergoing PCI, evolocumab started before PCI increased achievement of an LDL-C reduction of ≥50 % to below 1.4 mmol/L at 12 months compared with standard lipid-lowering care.

N

2,161patients

Design

International, investigator-initiated Phase IV PROBE RCT, 1:1, first evolocumab dose given before PCI, 12-month primary follow-up (clinical follow-up continuing to 2028)

Endpoint

Achievement of both a ≥50% LDL-C reduction from baseline and LDL-C <1.4 mmol/L (55 mg/dL) at 12 months; main clinical endpoint the composite of all-cause death or unplanned cardiovascular hospitalisation at 12 months

Relevance

2Important — one of several pillars.

ResultPrimary lipid endpoint met: 792/970 (81.6%) vs 370/934 (39.6%), adjusted OR 5.54 (95% CI 4.50–6.82), p<0.001; median LDL-C at 6 weeks 16 vs 56 mg/dL. No clinical benefit: death or unplanned cardiovascular hospitalisation at 12 months 159/1087 (14.6%) vs 165/1074 (15.4%), adjusted OR 0.94 (95% CI 0.73–1.19), p=0.59

Montalescot G, Ferrari E, Souteyrand G, et al. JAMA. 2026; published online 29 August. 10.1001/jama.2026.17302

Discussion & critique

Giving the PCSK9 antibody before the wire crosses does what the pharmacology promises: four in five reach the guideline target at a year against two in five, with a median LDL-C of 16 mg/dL at six weeks. What it does not do, over twelve months, is change death or cardiovascular readmission — an open-label trial powered for a laboratory endpoint, not for events. The lipid result is the argument for starting early; the clinical arm is the reminder that a year is short for a curve that separates late.