Cardiovascular Benefit of Colchicine in Relation to Baseline Risk: A Secondary Analysis of the LoDoCo2 Trial

BACKGROUND: The LoDoCo2 (Low-Dose Colchicine 2) trial showed that colchicine reduced the risk for cardiovascular events in patients with chronic coronary syndrome. Current guidelines recommend colchicine use in selected high-risk patients. The aim of this secondary analysis was to explore the relative and absolute benefits of colchicine according to baseline risk. METHODS: The LoDoCo2 trial randomized 5522 patients to colchicine 0.5 mg or placebo. The primary end point was a composite of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. First, a LoDoCo2 risk score was developed by Cox regression to identify high-risk features for the primary end point. Second, the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention was applied to explore robustness of findings. RESULTS: In the LoDoCo2 risk score, high-risk features were age ≥75, diabetes, and current smoker. In high-risk (≥1 high-risk feature), compared with low-risk (0 high-risk features) patients, colchicine was associated with consistent relative (high risk: hazard ratio [HR], 0.72 [95% CI, 0.56–0.94] versus low risk: HR, 0.67 [95% CI, 0.52–0.88]; P for interaction=0.73) and absolute benefits (high risk: HR, −1.33 [95% CI, −2.38 to −0.27] versus low risk: HR, −0.93 [95% CI −1.57 to −0.30] events per 100 person-years). Using the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention, consistent relative and absolute benefits were found in high-, intermediate-, and low-risk patients. CONCLUSIONS: In patients with chronic coronary syndrome, the relative and absolute benefits of colchicine were consistent in those at high, intermediate, and low risk for cardiovascular events. These findings support the use of colchicine across the spectrum of baseline risk. REGISTRATION: URL: https://www.anzctr.org.au; Unique identifier: 12614000093684.