RATIONALE: People with cardiovascular disease are at risk of recurrent major adverse cardiovascular events, and chronic low-grade inflammation may be a major underlying factor. Treatment with low-dose colchicine has been proposed for the secondary prevention of cardiovascular events in individuals at high cardiovascular risk. A previous Cochrane review showed considerable uncertainty regarding the benefits and harms of this approach.

OBJECTIVES: To evaluate the benefits and harms of low-dose colchicine in the prevention of cardiovascular events in adults with a history of stable CVD or following myocardial infarction or stroke.

SEARCH METHODS: We conducted a comprehensive search of the literature until February 2025 using Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the drugs@FDA database, references of key papers, and references of included studies.

ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) comparing the use of low-dose colchicine for a minimum of six months versus any control intervention in patients of any age with cardiovascular disease (i.e. history of stable cardiovascular disease, previous myocardial infarction or stroke).

OUTCOMES: Our critical outcomes were all-cause mortality, myocardial infarction, and serious adverse events. Our important outcomes were cardiovascular mortality, stroke, all-cause hospitalisations, coronary revascularisation (percutaneous coronary intervention (PCI)/angioplasty or coronary artery bypass graft (CABG)), quality of life, and gastrointestinal adverse events (i.e. diarrhoea, nausea, abdominal pain, or vomiting).

RISK OF BIAS: Two authors independently assessed the risk of bias using the Cochrane RoB2 tool.

SYNTHESIS METHODS: We conducted meta-analyses using the random-effects model. We generated forest plots to facilitate visualisation of the data. We did not perform any subgroup analysis. We used GRADE to assess the certainty of evidence for all critical outcomes and for cardiovascular mortality, stroke, and coronary revascularisation. This was carried out by two review authors working independently.

INCLUDED STUDIES: We included 12 studies involving 22,983 randomised participants. The follow-up in the studies ranged from 6 to 80 months. Overall, 11,524 participants were assigned to low-dose colchicine treatment and 11,459 were assigned to a control intervention, which constituted either usual care plus placebo or usual care only. The doses of colchicine used were 0.5 mg once or twice daily. At baseline, the mean age of participants ranged from 57 to 74 years. Most participants (79.4%) were male.

SYNTHESIS OF RESULTS: There is high-certainty evidence that low-dose colchicine treatment reduces the risk of myocardial infarction, with a risk ratio (RR) of 0.74 (95% confidence interval (CI) 0.57 to 0.96; 22,153 participants, 8 studies; I2 = 51%), yielding an absolute risk reduction of 9 fewer events (95% CI 16 fewer to 2 fewer) per 1000 patients, when the myocardial infarction rate is about 4% (36 events per 1000 patients) in the control group. There is also high-certainty evidence that low-dose colchicine reduces the risk of stroke with a RR of 0.67 (95% CI 0.47 to 0.95; 22,483 participants, 10 studies; I2 = 40%), yielding an absolute risk reduction of 8 fewer events (95% CI 12 fewer to 1 fewer) per 1000 patients, when the stroke rate is about 2% (22 events per 1000 patients) in the control group. There is high-certainty evidence that the use of low-dose colchicine does not increase the rate of serious adverse events (RR 0.98, 95% CI 0.94 to 1.02; 15,677 participants, 4 studies; I2 = 0%). However, gastrointestinal adverse events were more common under treatment with colchicine (RR 1.68, 95% CI 1.11 to 2.57; 22,185 participants, 10 studies; I2 = 91%). For all other outcomes assessed, the evidence is of moderate certainty. Colchicine probably results in little to no difference in all-cause mortality (RR 1.01, 95% CI 0.84 to 1.21; 22,747 participants, 10 studies; I2 = 1%; moderate-certainty evidence), in cardiovascular mortality (RR 0.94, 95% CI 0.73 to 1.22; 22,271 participants; 8 studies; I2 = 13%; moderate-certainty evidence), and coronary revascularisation (RR 0.83, 95% CI 0.64 to 1.08; 13,705 participants, 5 studies; I2 = 40%; moderate-certainty evidence). There is no evidence about the benefits or harms of colchicine on quality-of-life or on the risk of all-cause hospitalisation.

AUTHORS' CONCLUSIONS: People with cardiovascular disease using low-dose colchicine as secondary prevention for at least six months benefit from reduced rates of myocardial infarction and stroke, without an increase in serious adverse events. Moderate-certainty evidence did not show a benefit from low-dose colchicine for the risk of mortality (i.e. all-cause and cardiovascular mortality) or coronary revascularisation rates. Colchicine use was associated with an increased risk of gastrointestinal adverse events, which were typically described as mild and transient in nature. Additional studies are warranted to investigate the benefits and harms of low-dose colchicine in relevant subgroups and in specific indications, such as long-term use in individuals with stable coronary artery disease versus limited-time use following acute coronary syndrome.

FUNDING: Review author FE was supported by the Margot und Erich Goldschmidt & Peter René Jacobson Foundation. Review author CMS was supported by the Janggen Pöhn Foundation and the Swiss National Science Foundation (MD-PhD grant Number: 323530_221860).

REGISTRATION: This review is based on its protocol, which is available via DOI 10.1002/14651858.CD014808, and a previous review, which is available via DOI 10.1002/14651858.CD011047.pub2.

Family Medicine (FM)/General Practice (GP) rater

As a general practitioner who sees patients post MI/CVA in the community, it is useful to know that a low cost and well known medication can reduce the risk of recurrence of ACS/CVA for 6 months. This suggests that it may be an option to consider for the first 6 months post MI/CV, in addition to present usual measures.

General Internal Medicine-Primary Care(US) rater

Very helpful Cochrane review on benefits and risk of using low-dose colchicine for secondary CV prevention. As a primary care physician, I would be more comfortable in discussing and initiating it for appropriate patients.

Internal Medicine rater

Excellent Cochrane review of low-dose colchicine in secondary risk reduction in patients with CAD. This is an option I do and will offer patients in a shared-decision approach.