The Effects of Colchicine on Lipoprotein(a) and Oxidized Phospholipid Associated Cardiovascular Disease Risk.

Abstract

Aims: Inflammatory lipoprotein(a) [Lp(a)] and oxidized phospholipids (OxPLs) on lipoproteins convey residual cardiovascular disease risk. The LoDoCo2 (low-dose colchicine 2) trial showed that colchicine reduced the risk for cardiovascular events occurring on standard therapies in patients with chronic coronary disease (CCS). We explored the effects of colchicine on Lp(a) and oxidized lipoprotein associated risk in a LoDoCo2 biomarker subpopulation.

Methods: Lp(a), OxPLs on apolipoprotein(a) [OxPL-apo(a)] and apolipoprotein B (OxPL-apoB) levels were determined in the biomarker population of the LoDoCo2 trial (n = 1777). Cox regression analysis was used to compare the risk for the primary endpoint, consisting of myocardial infarction, ischemic stroke, or ischemia-driven revascularization by biomarker levels. Interactions between treatment, Lp(a) and OxPL levels were evaluated.

Results: Lp(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 to the lowest (Pinteraction=0.92 and 0.66). The absolute risk reduction for those with Lp(a) ≥125 nmol/L appeared higher compared to 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 colchicine may be more effective in subjects with heightened oxidation-driven inflammation.