Low dose colchicine for secondary prevention in patients with previous atherosclerotic event: a systematic review and meta-analysis of randomised trials

Abstract Introduction Colchicine is now recommended for secondary prevention in the latest European Cardiology Society guidelines for managing chronic coronary syndromes. Previously, two major trials and several meta-analyses, which included smaller randomised controlled trials (RCTs), showed that colchicine reduced major cardiovascular events (MACE), though it did not reduce cardiovascular (CV) mortality. Over the past year, three major trials have been published, all demonstrating no significant reduction in cardiovascular events. Two of these trials included patients with ischemic cerebrovascular events, broadening the context for colchicine’s in atherosclerotic disease. Aims To evaluate the efficacy and safety profile of low dose colchicine in secondary prevention among patients with a prior cardiovascular or cerebrovascular event. Methods A systematic search of electronic databases, including Medline and the Cochrane Library, was conducted to identify RCTs comparing colchicine with placebo or usual care in secondary prevention. The primary outcome was a composite measure of CV death, myocardial infarction or stroke. Risk of bias was assessed using the Cochrane quality assessment tool and outcomes were analyzed using an inverse-variance random-effects model. Results A total of 11 randomised controlled trials, involving 30753 patients, met the inclusion criteria. Of these, 15381 patients (50%) received colchicine, showing a lower risk of the primary outcome (6.2% vs. 7.2%; odds ratio (OR) = 0.80; 95% CI, 0.67–0.94; I² = 56%), reported MACE (7.4% vs. 9.0%; OR = 0.70; 95% CI, 0.57–0.85; I² = 72%), myocardial infarction (2.2% vs. 2.7%; OR = 0.76; 95% CI, 0.61–0.94; I² = 30%) and unstable angina (3.1% vs 4.0%; OR = 0.60; 95% CI, 0.42-0.86; I² =66%). There is a trend suggesting a potential benefit of colchicine in stroke prevention (2.8% vs. 3.2%; OR = 0.79; 95% CI, 0.61–1.04; I² = 49%). No significant benefit was found for cardiovascular mortality (1.3% vs. 1.4%; OR = 0.94; 95% CI, 0.77–1.15; I² = 0%) or all-cause mortality (2.5% vs. 2.6%; OR = 0.98; 95% CI, 0.79–1.21; I² = 39%). The colchicine group reported a higher incidence of gastrointestinal symptoms (12.7% vs. 9.6%; OR = 1.73; 95% CI, 1.25–2.39; I² = 91%). Non-cardiovascular mortality was similar across groups (1.2% vs 1.2%; OR = 1.03; 95% CI, 0.75-1.41; I² = 47%). Conclusion While colchicine did not reduce CV and all-cause mortality, it still demonstrated significant efficacy in secondary prevention of MACE, myocardial infarction and unstable angina, maintaining a relatively favourable safety profile.