- Design
- Secondary analysis of a randomised trial (FOURIER)
- Population
- 25,090 patients with stable atherosclerotic cardiovascular disease
- Primary outcome
- Incident safety events by baseline Lp(a)
- Effect
- No association with bleeding, stroke, cancer or AF; incident diabetes HR 1.05 (1.02–1.08) per 50 nmol/L lower
Lp(a)-lowering drugs are in outcome trials, and earlier studies linked very low Lp(a) with more diabetes. This FOURIER analysis measured baseline Lp(a) in 25,090 patients with stable atherosclerotic disease (median 37 nmol/L) and related it to safety outcomes.
Low Lp(a), including 13 nmol/L or less, was not associated with haemorrhagic stroke, serious bleeding, neurocognitive events, cancer or atrial fibrillation. Lower Lp(a) was associated with more diabetes, both at baseline (odds ratio 1.03 per 50 nmol/L lower) and during follow-up (hazard ratio 1.05, 95% CI 1.02 to 1.08, per 50 nmol/L lower).
Evolocumab, which lowered Lp(a) by a median 71 nmol/L in the top decile, did not raise diabetes risk (HR 0.72, 0.38 to 1.35). That suggests the diabetes link reflects naturally low Lp(a), possibly genetic, rather than lowering it with a drug — though the new agents cut Lp(a) far more than evolocumab does.
- Low natural Lp(a) was not linked with bleeding, haemorrhagic stroke, cancer or atrial fibrillation.
- Naturally low Lp(a) carried a small excess of diabetes, about 5% per 50 nmol/L lower.
- Evolocumab lowered Lp(a) without increasing diabetes risk in FOURIER.
- Watch for diabetes reporting in the Lp(a)-lowering outcome trials as they read out.
Why it matters
It answers an early safety question for the coming Lp(a)-lowering drugs.
Don't overread it
Natural low Lp(a) is not the same as drug-induced lowering, so this cannot settle the safety of the new agents.
The statistics, in plain English
A hazard ratio of 1.05 per 50 nmol/L is a small effect: going from 100 to 0 nmol/L would mean roughly 10% higher relative diabetes risk. The evolocumab interval (0.38 to 1.35) is wide and crosses 1, so it neither raises nor rules out a modest effect.
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