Highlights
- High-certainty evidence supports low-dose colchicine in reducing myocardial infarction and stroke risk in patients with established cardiovascular disease.
- No increase in serious adverse events was observed, but gastrointestinal side effects were more common.
- No significant reduction in all-cause or cardiovascular mortality, or coronary revascularisation rates.
- Further research is needed to clarify benefits in specific subgroups and long-term use in stable coronary artery disease.
Background
Recurrent major adverse cardiovascular events (MACEs) remain a significant cause of morbidity and mortality in individuals with established cardiovascular disease (CVD). Beyond traditional risk factors, chronic low-grade inflammation contributes to residual risk even under optimal secondary prevention regimens. Colchicine, an anti-inflammatory agent historically used for gout and pericarditis, has emerged as a candidate therapy to reduce post-event inflammation and thereby lower MACE rates. Earlier evidence was inconclusive, necessitating an updated synthesis of randomized controlled trials to inform clinical practice.
Study Design
This Cochrane systematic review and meta-analysis (published November 2025) included 12 randomized controlled trials (RCTs) involving 22,983 adult participants with a history of stable CVD, myocardial infarction, or stroke. Trials compared low-dose colchicine (0.5 mg once or twice daily) for ≥6 months versus control (usual care ± placebo). Outcomes included critical measures—all-cause mortality, myocardial infarction, and serious adverse events—and important measures such as cardiovascular mortality, stroke, coronary revascularisation, quality of life, and gastrointestinal adverse events.
Searches were conducted through CENTRAL, MEDLINE, EMBASE, and drugs@FDA, supplemented with reference checking. The mean participant age ranged from 57 to 74 years, with 79.4% male representation. Follow-up ranged between 6 and 80 months. Risk of bias was assessed independently by two reviewers using Cochrane RoB2, and GRADE methodology was applied to evaluate certainty of evidence.
Key Findings
Reduction in Myocardial Infarction
Low-dose colchicine significantly lowered myocardial infarction risk (high-certainty evidence), with a pooled risk ratio (RR) of 0.74 (95% CI: 0.57–0.96). This translates to an absolute risk reduction of approximately 9 fewer events per 1000 patients when baseline MI risk is 4% in control groups.
Reduction in Stroke
The therapy was also associated with reduced stroke incidence (RR: 0.67; 95% CI: 0.47–0.95), corresponding to 8 fewer events per 1000 patients when stroke risk is 2% among controls. Certainty was rated as high.
Serious Adverse Events
No increase in serious adverse events was found (RR: 0.98; 95% CI: 0.94–1.02). Evidence certainty was high.
Mortality and Revascularisation
Moderate-certainty evidence indicated little or no impact on all-cause mortality (RR: 1.01; 95% CI: 0.84–1.21) and cardiovascular mortality (RR: 0.94; 95% CI: 0.73–1.22). No significant difference was seen in coronary revascularisation rates (RR: 0.83; 95% CI: 0.64–1.08).
Gastrointestinal Adverse Events
Colchicine increased gastrointestinal adverse events such as diarrhoea and nausea (RR: 1.68; 95% CI: 1.11–2.57). These were generally mild and transient but may impact tolerability.
Evidence Gaps
No evidence was available for effects on quality of life or all-cause hospitalisation. The authors recommend targeted studies in underrepresented subgroups and varying clinical contexts (e.g., post-acute coronary syndrome vs. stable CAD).
Expert Commentary
These findings support an anti-inflammatory approach to secondary cardiovascular prevention. The high-certainty reductions in MI and stroke underscore colchicine’s mechanistic plausibility—likely driven by inhibition of tubulin polymerisation, which downregulates inflammatory cytokines including interleukin-1β. Clinical uptake may be moderated by gastrointestinal intolerance and absence of mortality benefit in current evidence. As most trial participants were male, sex-specific outcomes require exploration. Additionally, the high I² for gastrointestinal events suggests heterogeneity in reporting or susceptibility, warranting nuanced patient selection.
Guideline committees considering colchicine for secondary prevention must balance absolute risk reductions against tolerability and healthcare system capacity for long-term patient monitoring, especially in polypharmacy contexts.
Conclusion
Low-dose colchicine represents a viable adjunct in secondary prevention for patients with established CVD, offering consistent benefits in reducing MI and stroke without increasing serious adverse events. However, its gastrointestinal side effect profile necessitates caution, and absence of mortality benefit highlights the need for continued surveillance and targeted trials.
Clinicians should integrate these findings into evidence-based discussions with patients, considering individual baseline risks, comorbidities, and therapy goals. The evolving anti-inflammatory paradigm in cardiology may see colchicine as an accessible, low-cost intervention for select patient groups.
Funding and Registration
Funding: Margot und Erich Goldschmidt & Peter René Jacobson Foundation; Janggen Pöhn Foundation; Swiss National Science Foundation (MD-PhD grant Number: 323530_221860).
Registration: DOI 10.1002/14651858.CD014808 and DOI 10.1002/14651858.CD011047.pub2.
References
Ebrahimi F, Ebrahimi R, Beer M, Schönenberger CM, Ewald H, Briel M, Janiaud P, Hirt J, Hemkens LG. Colchicine for the secondary prevention of cardiovascular events. Cochrane Database Syst Rev. 2025 Nov 13;11(11):CD014808. doi: 10.1002/14651858.CD014808.pub2. PMID: 41224205; PMCID: PMC12611456.
