Side Effects of Low‐Dose Colchicine in Chronic Coronary Disease: A Post Hoc Analysis of the LoDoCo2 Trial

BACKGROUND: Low-dose colchicine reduces cardiovascular events in patients with chronic coronary disease. However, side effects may compromise compliance and lead to discontinuation of treatment. Therefore, we aimed to assess the incidence of side effects leading to discontinuation of treatment in the LoDoCo2 (Low-Dose Colchicine 2) trial. METHODS: The LoDoCo2 trial was a randomized controlled trial evaluating colchicine versus placebo in patients with chronic coronary disease. Participants entered a 30-day open-label run-in phase during which all participants received colchicine 0.5 mg once daily, followed by randomization to colchicine or placebo. Tolerability-related side effects leading to treatment discontinuation were evaluated at the end of the 30-day run-in phase and during the randomized phase (median follow-up, 29.5 [interquartile range, 21.6-47.4] months). Cumulative incidence of side effects was presented using Kaplan-Meier curves and compared by treatment arm using Cox proportional hazards models. RESULTS: During the 30-day run-in phase, 618 of 6519 (9.5%) participants reported side effects. Women had a higher risk of side effects than men during the 30-day run-in phase (odds ratio, 1.53 [95% CI, 1.23-1.89]). After randomization, 114 participants (4.2%) in the colchicine group and 120 (4.4%) in the placebo group discontinued treatment due to side effects (hazard ratio [HR], 0.95 [95% CI, 0.73-1.22]). Gastrointestinal symptoms were most common (colchicine 2.0% versus placebo 1.7%) followed by myalgia (colchicine 1.2% versus placebo 1.6%). No differences in the risk of side effects between colchicine and placebo were seen for any of the subgroups. Women did have a higher risk of reporting side effects compared with men, regardless of assigned treatment (HR, 1.66 [95% CI, 1.22-2.25]). CONCLUSIONS: In patients with chronic coronary disease that tolerated initial treatment with low-dose colchicine, long-term discontinuation due to side effects was uncommon and did not differ between colchicine and placebo. REGISTRATION: URL: https://www.anzctr.org/au; Unique identifier: ACTRN12614000093684.