Evolocumab before PCI for high-risk MI reached LDL targets but did not reduce events at one year

Design

Phase 4, randomised, open-label, blinded endpoint adjudication

Population

2,161 adults with high-risk STEMI or NSTEMI undergoing PCI

Primary outcome

LDL <55 mg/dL with ≥50% reduction at 12 months

Effect

82% vs 40%, adjusted OR 5.54 (4.50 to 6.82); death or CV admission 14.6% vs 15.4%, OR 0.94 (0.73 to 1.19)

AMUNDSEN randomised 2,161 patients with high-risk STEMI or NSTEMI at 48 sites in 6 countries to evolocumab 140 mg every 2 weeks, first dose before PCI, plus high-intensity oral therapy, or standard care alone. It was open-label with blinded endpoint adjudication.

The primary outcome, LDL below 55 mg/dL with at least a 50% fall at 12 months, was reached by 82% against 40% (adjusted OR 5.54). Median LDL at 6 weeks was 16 against 56 mg/dL. Death or unplanned cardiovascular admission occurred in 14.6% against 15.4% (OR 0.94, 0.73 to 1.19).

The trial shows that giving a PCSK9 inhibitor in the catheter laboratory gets patients to target fast. It does not show an acute pleiotropic benefit within a year, which is the argument usually made for starting it before reperfusion. Long-term benefit from lower LDL is still expected from the outcome trials.

• Start high-intensity statin before discharge in every MI patient
• Check LDL at 4 to 6 weeks and escalate if above target
• Do not delay reperfusion to give a PCSK9 inhibitor
• Consider early PCSK9 inhibition where follow-up is unreliable and LDL is far above target

Why it matters

It removes the case for a very early, pre-PCI start of PCSK9 inhibition on grounds of acute benefit.

Don't overread it

The trial was not powered to show a one-year clinical difference; it does not argue against PCSK9 inhibitors for long-term risk.

The statistics, in plain English

The odds ratio of 5.54 for reaching target is a large, certain effect on a surrogate. The clinical odds ratio of 0.94 with an interval of 0.73 to 1.19 means the trial could not tell a 27% reduction from a 19% increase. One year is short for LDL lowering to show benefit, so a neutral clinical result here is expected rather than surprising.

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