Pre-PCI Evolocumab Improves LDL-C After Acute MI

Key Takeaways

• Among patients undergoing PCI for high-risk acute MI, starting evolocumab before PCI with standard care was associated with greater attainment of the combined one-year LDL-C target than standard care alone.
• Six-week median LDL-C was distinctly lower with evolocumab plus standard care than with standard care alone.
• The separate one-year composite of death or unplanned cardiovascular hospitalization did not differ significantly between treatment groups.

After acute myocardial infarction (MI), guidelines position PCSK9 inhibitors as second- or third-line therapy. Whether starting one in the catheterization laboratory, before percutaneous coronary intervention (PCI), improves low-density lipoprotein cholesterol (LDL-C) control and one-year outcomes is unknown.

Investigators randomized 2,161 adults equally in the prospective, international phase 4 AMUNDSEN randomized clinical trial at 48 sites in six countries. Treatment was open-label, with blinded endpoint adjudication. Participants undergoing PCI had high-risk ST-segment elevation myocardial infarction (STEMI) or non–ST-segment elevation myocardial infarction (NSTEMI).

Evolocumab 140 mg subcutaneously every two weeks for one year, beginning before PCI, was added to standard care. The comparison group received standard care alone. Standard care included high-intensity oral lipid-lowering treatment and permitted later PCSK9 inhibitor use in controls when indicated.

The primary lipid endpoint required both LDL-C below 55 mg/dL and a reduction of at least 50% from baseline at 12 months. The separate main clinical endpoint was all-cause death or unplanned cardiovascular hospitalization at the same follow-up.

Among patients evaluable for the primary lipid endpoint, 792/970 (82%) receiving evolocumab plus standard care met both criteria, compared with 370/934 (40%) receiving standard care. The adjusted odds ratio (OR) was 5.54 (95% confidence interval [CI] 4.50–6.82), P<.001.

At six weeks, median LDL-C was 16 mg/dL with evolocumab plus standard care versus 56 mg/dL with standard care.

For the separate one-year composite of all-cause death or unplanned cardiovascular hospitalization, events were reported in 14.6% assigned to evolocumab plus standard care and 15.4% assigned to standard care. The adjusted OR was 0.94 (95% CI 0.73–1.19), P=.59. The difference was not statistically significant.

The marked separation in lipid-target attainment did not establish a reduction in the clinical composite. Treatment allocation was open-label, although endpoint adjudication was blinded; the comparison group received active standard care rather than placebo. Fewer patients were evaluable for the lipid endpoint than were randomized; clinical-event analysis denominators were not specified in the available report.

The authors concluded that evolocumab initiated before PCI alongside high-intensity lipid-lowering treatment produced rapid, sustained LDL-C reduction, while no clinical benefit was detected during the first year of follow-up.

Clinician Questions

Which high-risk STEMI or NSTEMI patients were eligible for pre-PCI evolocumab in AMUNDSEN?

Among adults with acute MI undergoing PCI, pre-PCI evolocumab was evaluated in patients with high-risk STEMI who were older than 55 years and in patients with NSTEMI who had at least one additional high-risk characteristic. Those criteria do not encompass all patients with acute MI.

What did AMUNDSEN investigators conclude about acute pleiotropic effects of PCSK9 inhibition after MI?

For patients with acute MI treated with evolocumab before PCI in addition to standard care, investigators interpreted the absence of detected first-year clinical benefit as arguing against clinically meaningful acute pleiotropic effects of PCSK9 inhibition beyond standard care.