PCSK9 inhibitors are usually second or third line after myocardial infarction, which leaves months of inadequate LDL control while therapy is escalated. AMUNDSEN tested moving the decision to the catheterisation laboratory. At 48 sites in six countries, 2,161 adults with high-risk STEMI or NSTEMI were randomised to evolocumab 140 mg every two weeks for a year — first injection before PCI — plus standard care, or to standard care alone, which itself included high-intensity oral lipid-lowering and PCSK9 inhibition where guidelines indicated it.
Biochemically it was emphatic. The primary outcome of LDL below 55 mg/dL and at least a 50% reduction at 12 months was reached by 82% on evolocumab against 40% on standard care (adjusted OR 5.54, 95% CI 4.50 to 6.82, p<0.001). At six weeks, median LDL was 16 mg/dL against 56 mg/dL. Clinically it was flat. Death or unplanned cardiovascular hospitalisation at 12 months occurred in 14.6% against 15.4% (adjusted OR 0.94, 0.73 to 1.19, p=0.59).
The useful conclusion is a negative one. There is no acute pleiotropic benefit from starting a PCSK9 inhibitor at the moment of reperfusion — no plaque-stabilising bonus that shows up inside a year. The rationale for early PCSK9 inhibition therefore returns to what it always was: getting LDL down and keeping it there, whose benefits accrue over years, not months. A one-year trial is the wrong instrument to measure that.
In Indian practice the cost calculus is different again and pushes the same way. If the argument for injecting in the cath lab was an early clinical dividend, that argument is gone. What remains is achieving target and sustaining it, which for most patients means getting maximal oral therapy right first and reserving the injectable for those who genuinely will not reach target without it.
- Do not start a PCSK9 inhibitor peri-procedurally expecting an early clinical benefit; there was none at one year.
- Optimise high-intensity statin plus ezetimibe first, and check the lipid panel at 4 to 6 weeks.
- Only 40% of the standard-care arm reached target at a year — that gap is the real problem to fix.
- Where a PCSK9 inhibitor is indicated, start it because the patient will not otherwise reach target, not because of timing.
- Judge these agents on sustained LDL control over years, which is where their outcome evidence sits.
The statistics, in plain English
The clinical result is a confidence interval of 0.73 to 1.19 around an odds ratio of 0.94. That interval spans 1.0, meaning no difference is entirely compatible with the data — but it also leaves room for up to a 27% relative reduction, so this is not proof of no benefit, only a failure to find one within a year. Contrast that with the biochemical result, where the interval of 4.50 to 6.82 sits nowhere near 1.0. The drug did exactly what it is supposed to do; the trial simply was not long enough for that to translate.
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