Safety of low Lp(a): no excess of bleeding, malignancy, neurocognitive events or AF, but more diabetes: FOURIER (Gencer et al., EHJ 2026)

Original title: Safety of low lipoprotein(a) levels: the FOURIER trial

Eur Heart J · 3 June 2026 · 7

Gencer B, Giugliano RP, Ran X, Mach F, Stroes ESG, Gouni-Berthold I, Češka R, Ezhov MV, Jukema JW, Jensen HK, Tokgözoğlu SL, Huber K et al.

In 25,090 FOURIER patients, low baseline Lp(a) (including 13 nmol/L or below) carried no excess risk of haemorrhagic stroke, serious bleeding, neurocognitive events, malignancy or atrial fibrillation; each 50 nmol/L lower Lp(a) was associated with 3 percent higher odds of prevalent and 5 percent higher risk of incident diabetes, and evolocumab did not raise diabetes risk even where it lowered Lp(a) by a median 71 nmol/L. Reassuring for the outcomes trials, with the diabetes association still to be watched.

Original abstract

Background And Aims: Lipoprotein(a) (Lp(a)) is considered a causal risk factor for atherogenesis. A higher prevalence of certain adverse events, including diabetes mellitus (DM), has been reported for patients with low Lp(a) concentrations. Therapeutics that lower Lp(a) are now in clinical testing. Thus, the association between lower Lp(a) concentration and safety outcomes is of clinical importance.

Methods: The FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial randomized 27 564 patients with stable atherosclerotic cardiovascular disease (ASCVD) to evolocumab versus placebo on a background of statin therapy. The relationship between Lp(a) and the risk of prevalent and incident adverse outcomes of interest was examined, adjusting for relevant predictors.

Results: Lp(a) was assessed in 25 090 participants at baseline (median 37 nmol/L, interquartile range 13-165). There was no association between Lp(a) concentration and incident risk of haemorrhagic stroke, serious bleeding, neurocognitive events, malignancy, or atrial fibrillation, including those with Lp(a) levels ≤13 nmol/L. There was an inverse association between lower baseline Lp(a) levels and prevalent DM at baseline (adjusted odds ratio 1.03, 95% confidence interval [CI] 1.02-1.04, P < .001; for every 50 nmol/L lower Lp(a)), as well as the incident risk of developing DM during follow-up (adjusted hazard ratio [HR] 1.05, 95% CI 1.02-1.08, P = .002; for every 50 nmol/L lower Lp(a)), with consistent results by treatment arm. Evolocumab did not increase the risk of DM irrespective of baseline Lp(a), even in participants in the top decile of baseline Lp(a) (adjusted HR .72, 95% CI .38-1.35) in whom evolocumab reduced Lp(a) by a median of 71 nmol/L.

Conclusions: In patients with ASCVD, low Lp(a) concentration was not associated with an increased risk of most adverse safety outcomes, but lower Lp(a) was associated with an increased risk of prevalent and incident DM.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.