548 Colchicine in patients with coronary artery disease: a meta-analysis of randomized trials

Abstract

Abstract Aims The aim of this study was to provide a systematic appraisal of the effects of colchicine treatment on cardiovascular outcomes, adverse events, and mortality in patients with coronary artery disease. Methods and results We performed a meta-analysis of randomized controlled trials (RCTs) that compared add-on colchicine to standard treatment vs. standard treatment in patients with coronary artery disease. Mixed-effects Poisson regression model with random intervention effects was used to estimate the pooled incidence rate ratios (IRR) with 95% confidence intervals (CI). The number needed to treat for an additional beneficial outcome (NNTB) or for an additional harmful outcome (NNTH) were calculated. Prespecified subgroup analyses according to colchicine dose (e.g. <1 mg/daily or ≥ 1 mg/daily) and the type of clinical syndrome [e.g. acute coronary syndrome (ACS) or chronic coronary syndrome (CCS)] were performed. Ten RCTs were identified, including 12 819 participants with a median follow-up of 6 months. Add-on colchicine, compared to standard treatment, was associated with a lower risk of major adverse cardiovascular events (IRR: 0.69, 95% CI: 0.60–0.79, NNTB = 28), myocardial infarction (IRR: 0.77, 95% CI: 0.64–0.93, NNTB = 95), and ischaemic stroke (IRR: 0.48, 95% CI: 0.30–0.76, NNTB = 155), while it was associated with a higher risk of gastrointestinal adverse events (IRR: 1.69, 95% CI: 1.12–2.54, NNTH = 10). Colchicine use did not affect all-cause death (IRR: 1.09, 95% CI: 0.85–1.40), or cardiovascular death (IRR: 0.75, 95% CI: 0.51–1.12), while it was associated with a higher risk of non-cardiovascular death (IRR: 1.45, 95% CI: 1.04–2.02, NNTH = 396). In the subgroup analysis of colchicine dose, a significant interaction was found with the risk of gastrointestinal adverse events (IRR: 1.03, 95% CI: 0.91–1.15, in patients receiving colchicine <1 mg/daily; IRR: 2.91, 95% CI: 1.91–4.44, in patients receiving colchicine ≥1 mg/daily, p for interaction <0.0001), while there was no evidence for a modification of treatment effect for the remaining endpoints. In the subgroup analysis of the clinical syndrome, there was little evidence for an interaction with the risk of myocardial infarction (IRR: 0.91, 95% CI: 0.71–1.18, in patients presenting with ACS; IRR: 0.65, 95% CI: 0.50–0.84, in patients presenting with CCS, p for interaction = 0.07), while there was no evidence for a modification of treatment effect for the remaining endpoints. Conclusions This meta-analysis of RCT provides evidence for a significant clinical benefit of add-on colchicine in terms of risk reduction of cardiovascular events in patients with coronary artery disease, that largely outweigh a potential harmful effect of colchicine on the risk of non-cardiovascular death. Colchicine is associated with a higher risk of gastrointestinal adverse effects that can be prevented by using a low-dose regimen (e.g. <1 mg daily).