Cardiovascular Benefit and Gastrointestinal Risk of Colchicine in Secondary Prevention: Risk Associated with Dose and...

This meta-analysis aims to evaluate the efficacy and safety of colchicine for the secondary prevention of cardiovascular and cerebrovascular diseases, and examines how dose and treatment duration modify its risk-benefit profile.

A meta-analysis comparing colchicine to placebo or standard care was performed. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. The secondary endpoint was expanded MACE (eMACE), defined as MACE plus ischemia-driven coronary revascularization.

Colchicine significantly reduced the risk of MACE (relative risk [RR] 0.83, 95% confidence interval [CI] 0.72-0.96) and eMACE (RR 0.78, 95% CI 0.64-0.96), with benefits driven by reductions in non-fatal MI and ischemia-driven coronary revascularization. No significant effect was observed on cardiovascular or all-cause mortality. Colchicine increased gastrointestinal adverse reactions (RR 1.90, 95% CI 1.41-2.55) and drug-related adverse event (DAE)-related colchicine discontinuation (RR 1.54, 95% CI 1.06-2.25). Sensitivity analyses revealed that the guideline-recommended dosage (0.5 mg once daily) for > 6 months maintained cardiovascular benefit (MACE RR 0.77, 95% CI 0.62-0.96), while gastrointestinal risk (RR 1.51, 95% CI 0.97-2.33) and DAE-related colchicine discontinuation risk (RR 1.42, 95% CI 0.80-2.51) became non-significant.

Colchicine provides lasting benefit for patients with cardiovascular and cerebrovascular diseases. Gastrointestinal risk is dose and time dependent, and higher early in treatment. Tolerating and maintaining long-term standard-dose therapy improves the benefit-risk balance. These findings highlight the early treatment phase as a period of higher gastrointestinal risk, suggesting that strategies to support adherence during this period warrant further investigation.

PROSPERO registration number CRD42024623329.