secondary prevention

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.