Inflammation
Colchicine's cardiovascular benefit in the LoDoCo2 trial was greatest in patients with elevated Lp(a), and even more clearly modified by oxidised phospholipids on ApoB (Eur J Prev Cardiol 2025)
Original title: The effects of colchicine on lipoprotein(a)- and oxidized phospholipid-associated cardiovascular disease risk
This biomarker substudy of the LoDoCo2 trial (n = 1,777), which showed low-dose colchicine reduces cardiovascular events in chronic coronary syndrome on top of standard therapy, examined whether colchicine's benefit varies by Lp(a) and oxidised phospholipid (OxPL) levels. Lp(a), OxPL-apo(a) and OxPL-apoB were similar between the colchicine and placebo groups at baseline. Colchicine consistently reduced risk of the primary endpoint (myocardial infarction, ischaemic stroke, or ischaemia-driven revascularisation) regardless of Lp(a) status (below or at/above 125 nmol/L) or OxPL-apo(a) tertile (P for interaction 0.92 and 0.66), but the absolute risk reduction was numerically greater in patients with Lp(a) at or above 125 nmol/L than below it (4.4% vs. 2.4%). A significant treatment interaction was found for OxPL-apoB (P for interaction = 0.04), with colchicine's benefit concentrated in the highest OxPL-apoB tertile. The authors conclude colchicine benefits patients regardless of Lp(a) status but may work best in those whose residual risk is driven by oxidation-associated inflammation.
Original abstract
Aims: Inflammatory lipoprotein(a) [Lp(a)] and oxidized phospholipids (OxPLs) on lipoproteins convey residual cardiovascular disease risk. The low-dose colchicine 2 (LoDoCo2) trial showed that colchicine reduced the risk of cardiovascular events occurring on standard therapies in patients with chronic coronary syndrome (CCS). We explored the effects of colchicine on Lp(a)- and oxidized lipoprotein-associated risk in a LoDoCo2 biomarker subpopulation.
Methods And Results: Lipoprotein(a) and OxPLs on apolipoprotein(a) [OxPL-apo(a)] and apolipoprotein B-100 (OxPL-apoB) levels were determined in the biomarker population of the LoDoCo2 trial (n = 1777). The Cox regression analysis was used to compare the risk of the primary endpoint, consisting of myocardial infarction, ischaemic stroke, or ischaemia-driven revascularization by biomarker levels. Interactions between treatment, Lp(a), and OxPL levels were evaluated. Lipoprotein(a), OxPL-apo(a), and OxPL-apoB levels were similar between the colchicine and placebo groups. Consistent risk reduction by colchicine was observed in those with Lp(a) < 125 nmol/L and ≥125 nmol/L and the highest OxPL-apo(a) tertile compared with the lowest (Pinteraction = 0.92 and 0.66). The absolute risk reduction for those with Lp(a) ≥ 125 nmol/L appeared higher compared with those with Lp(a) < 125 nmol/L (4.4% vs. 2.4%). A treatment interaction for colchicine was found in those with the highest OxPL-apoB tertile vs. the lowest (Pinteraction = 0.04).
Conclusion: In patients with CCS, colchicine reduces cardiovascular disease risk in those with and without elevated Lp(a) but absolute benefits appeared higher in those with Lp(a) ≥ 125 nmol/L. Patients with higher levels of OxPL-apoB experienced greater benefit of colchicine, suggesting that colchicine may be more effective in subjects with heightened oxidation-driven inflammation.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.