Efficacy of colchicine in reducing cardiovascular events in patients with low-to-normal LDL-C levels

Abstract Introduction / Background High-sensitivity C-reactive protein (hs-CRP) is a potent biomarker and independent predictor of cardiovascular disease, reflecting the inflammatory nature of atherosclerosis. High-sensitivity assays are essential because they accurately detect low-range elevations associated with chronic inflammation and increased cardiovascular risk. The JUPITER trial previously evaluated whether rosuvastatin could reduce cardiovascular events in individuals with low-to-normal LDL-C but elevated hs-CRP. Purpose This trial was designed to test the hypothesis that colchicine therapy reduces major cardiovascular events in individuals whose risk is driven primarily by inflammation, namely those with elevated hs-CRP, despite having normal or low-to-normal LDL-C. Methods We enrolled 140 apparently healthy men aged ≥50 years and 70 women aged ≥60 years with low-to-normal LDL-C (130 mg/dL) and hs-CRP 2.0 mg/L. Participants were randomly assigned to receive 0.5 mg colchicine daily or a matching placebo. The primary endpoint was the first occurrence of a composite major cardiovascular event, including nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, arterial revascularization, or confirmed cardiovascular death. Follow-up visits were conducted at 6, 12, and 18 months. During each visit, primary endpoints, the composite of all primary endpoints, all-cause mortality, LDL-C, and hs-CRP levels were assessed. Results In the colchicine group, 2 nonfatal myocardial infarctions, no nonfatal strokes, 3 hospitalizations for unstable angina, 5 arterial revascularizations, and 1 cardiovascular death occurred, along with 1 all-cause death. In the placebo group, 6 nonfatal myocardial infarctions, 1 nonfatal stroke, 12 hospitalizations for unstable angina, 15 arterial revascularizations, and 2 cardiovascular deaths were recorded, with 3 all-cause deaths. The primary composite endpoint occurred in 11 colchicine recipients versus 36 placebo participants. Colchicine therapy resulted in a 27% reduction in LDL-C and a 42% reduction in hs-CRP, whereas minimal changes were observed in the placebo group (P 0.001). Conclusion Colchicine therapy significantly reduced major cardiovascular events in patients with low-to-normal LDL-C but elevated hs-CRP. Nonfatal myocardial infarction, unstable angina, arterial revascularization, and the composite primary endpoint were decreased, with clinically meaningful reductions in both LDL-C and hs-CRP, highlighting anti-inflammatory and lipid-lowering effects. Colchicine may therefore be an effective preventive therapy for cardiovascular events in individuals whose risk is primarily driven by inflammation despite normal lipid levels. As the study is ongoing, further follow-up and additional analyses are required to assess long-term outcomes and clinical implications. The results presented represent the primary outcomes observed to date.