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.
| Discipline Area | Score |
|---|---|
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
| Internal Medicine |  |
| Cardiology | |
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.
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.
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.
Variability has been observed in the clinical benefit of colchicine across studies and patient subgroups, suggesting that the anti-inflammatory effects of colchicine may not be universally beneficial nor equally potent in all cardiovascular patients. While both COLCOT and LoDoCo2 demonstrated a significant reduction in cardiovascular endpoints, other studies have not replicated these benefits to the same extent, and some have reported a higher incidence of adverse gastrointestinal events or infections. This heterogeneity may be attributable to differences in baseline inflammatory burden, genetic polymorphisms that affect colchicine metabolism, or comorbidities that influence the drug’s response.
In addition, interactions between colchicine and other pharmacotherapies—such as statins (e.g., simvastatin or atorvastatin) or antiplatelet agents—may modify its efficacy or toxicity profile. These findings highlight the need to identify specific biomarkers or clinical characteristics that could predict the response to colchicine, enabling a more personalized approach to its use in the treatment of cardiovascular diseases.
According to the Class IIa recommendation (Level of Evidence A) established in the 2024 Guidelines published by the European Society of Cardiology (ESC), colchicine should be prescribed to adult patients with chronic coronary syndromes due to atherosclerotic coronary artery disease. According to the guidelines, patients with chronic coronary syndrome and atherosclerotic coronary artery disease should consider taking a low dose of colchicine (0.5 mg per day) to reduce the incidence of myocardial infarction and stroke. This recommendation emerged from the results of the COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low-Dose Colchicine 2) trials.
Regarding acute coronary syndromes (ACS), the 2023 Guidelines of the European Society of Cardiology (ESC) state that colchicine may be considered, especially if other risk factors are not adequately controlled or if recurrent cardiovascular events occur despite optimal therapy (Class IIb recommendation). CLEAR-SYNERGY was the largest completed trial of anti-inflammatory therapy conducted in the context of acute coronary ischemia. Therefore, until more data become available, the use of targeted anti-inflammatory therapy during acute ischemia will remain limited.
For both indications, the evidence in this field is insufficient; neither the LoDoCo nor the COLCOT trials selected patients based on high inflammatory risk. Consequently, stable chronic atherosclerosis (where the benefits of anti-inflammatory therapy are consistent) should be addressed separately from acute coronary ischemia (where the net benefits and risks of anti-inflammatory therapy remain uncertain, and more research is needed).
ORIGINAL COMMENT (translated using AI): Se ha observado variabilidad en el beneficio clínico de la colchicina, entre estudios y subgrupos de pacientes, lo que sugiere que los efectos antiinflamatorios de la colchicina podrían no ser universalmente beneficiosos ni igualmente potentes en todos los pacientes cardiovasculares.
Si bien tanto COLCOT como LoDoCo2 demostraron una reducción significativa en los criterios de valoración cardiovasculares, otros estudios no han replicado estos beneficios con la misma magnitud, y algunos han observado una mayor incidencia de eventos gastrointestinales adversos o infecciones.
Esta heterogeneidad puede atribuirse a diferencias en la carga inflamatoria basal, polimorfismos genéticos que afectan el metabolismo de la colchicina o comorbilidades que influyen en la respuesta al fármaco.
Además, la interacción entre la colchicina y otras farmacoterapias, como las estatinas (ej: simvastatina o atorvastatina) o los antiagregantes plaquetarios, podría modificar su eficacia o perfil de toxicidad.
Estos hallazgos subrayan la necesidad de identificar biomarcadores específicos o características clínicas que puedan predecir la respuesta a la colchicina, permitiendo un enfoque más personalizado para su uso en el tratamiento de enfermedades cardiovasculares.
De acuerdo con la indicación de clase IIa (nivel de evidencia A) establecida en las Guías publicadas por la Sociedad Europea de Cardiología (ESC) en 2024, la colchicina debe prescribirse a pacientes adultos con síndromes coronarios crónicos debido a enfermedad coronaria aterosclerótica.
Según las guías, los pacientes con síndrome coronario crónico y enfermedad coronaria aterosclerótica deberían considerar la administración de una dosis baja de colchicina (0,5 mg al día) para reducir la incidencia de infarto de miocardio y accidente cerebrovascular.
Esta recomendación surgió tras los resultados del ensayo COLCOT (Colchicine Cardiovascular Outcomes Trial), el ensayo LODOCO2 (Low-Dose Colchicine 2)
En cuanto a los síndromes coronarios agudos (SCA), en las Guías de la Sociedad Europea de Cardiología (ESC) en 2023 se afirma que se puede considerar la colchicina, especialmente si otros factores de riesgo no están suficientemente controlados o si se producen eventos de enfermedad cardiovascular recurrentes con una terapia óptima (indicación de clase IIb). CLEAR-SYNERGY fue el mayor ensayo completo de terapia antiinflamatoria realizado en el contexto de la isquemia coronaria aguda.
Por tanto, hasta que se disponga de más datos, el uso de la terapia antiinflamatoria dirigida durante la isquemia aguda seguirá siendo limitado
Para ambas indicaciones, la evidencia en este campo es insuficiente, ni los ensayos LoDoCo ni los ensayos COLCOT seleccionaron a los pacientes según su elevado riesgo inflamatorio
Por lo que se deberá abordar por separado la aterosclerosis crónica estable (con beneficios de la terapia antiinflamatoria consistentes) de la isquemia coronaria aguda (con beneficios y riesgos netos de la terapia antiinflamatoria inciertos y donde se necesita más investigación).