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Colchicine in Patients with Chronic Coronary Disease
Open accessAbstract
BACKGROUND: Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent myocardial infarction, but evidence of such a risk reduction in patients with chronic coronary disease is limited. METHODS: In a randomized, controlled, double-blind trial, we assigned patients with chronic coronary disease to receive 0.5 mg of colchicine once daily or matching placebo. The primary end point was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. The key secondary end point was a composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke. RESULTS: A total of 5522 patients underwent randomization; 2762 were assigned to the colchicine group and 2760 to the placebo group. The median duration of follow-up was 28.6 months. A primary end-point event occurred in 187 patients (6.8%) in the colchicine group and in 264 patients (9.6%) in the placebo group (incidence, 2.5 vs. 3.6 events per 100 person-years; hazard ratio, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P<0.001). A key secondary end-point event occurred in 115 patients (4.2%) in the colchicine group and in 157 patients (5.7%) in the placebo group (incidence, 1.5 vs. 2.1 events per 100 person-years; hazard ratio, 0.72; 95% CI, 0.57 to 0.92; P = 0.007). The incidence rates of spontaneous myocardial infarction or ischemia-driven coronary revascularization (composite end point), cardiovascular death or spontaneous myocardial infarction (composite end point), ischemia-driven coronary revascularization, and spontaneous myocardial infarction were also significantly lower with colchicine than with placebo. The incidence of death from noncardiovascular causes was higher in the colchicine group than in the placebo group (incidence, 0.7 vs. 0.5 events per 100 person-years; hazard ratio, 1.51; 95% CI, 0.99 to 2.31). CONCLUSIONS: In a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo. (Funded by the National Health Medical Research Council of Australia and others; LoDoCo2 Australian New Zealand Clinical Trials Registry number, ACTRN12614000093684.).
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“The efficacy of GLP-1 medications is consistent with actions of other antiinflammatory agents, such as IL-1 antagonists and colchicine, in reducing cardiovascular events (63, 64).”
From Antiinflammatory actions of glucagon-like peptide-1–based therapies beyond metabolic benefits (2025) · cites this paper as [63]
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“The CTTC analysis reported that the benefits of lowering LDL-C level were consistent across a wide spectrum of baseline risk varying from less than 5% to 30% or greater.”
From Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients (2023) · cites this paper as [24]
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“The CTTC analysis showed a 22% reduction in major coronary events for each 38.7-mg/dL (1-mmol/L) decrease in LDL-C level and a 15% reduction in vascular death.”
From Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients (2023) · cites this paper as [24]
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“…enzyme for the immune system and is primarily involved in receptor-mediated signal transduction, through the signal transducer and activator of the transcription (STAT) protein family 23 , of which STATS 1–6 were significantly upregulated in the presence of LPStreated THP1 M ɸ s and VSMCs (Fig.”
Cells in Atherosclerosis: Focus on Cellular Senescence from Basic Science to Clinical Practice
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“…chronic coronary artery disease and receiving colchicine had a 31% reduction in the incidence of the primary composite endpoint of cardiovascular death, myocardial infarction, ischemic stroke, and ischemic-driven coronary revascularization compared with patients receiving placebo [10,168,169].”
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Anti-inflammatory pharmacotherapy in patients with cardiovascular disease
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“Study CANTOS [81] CIRT [89] LODOCO1 [90] LODOCO2 [91] COLCOT [92] COPS [93]”
BackgroundInfluentialNeglia, D., Aimo, A., Lorenzoni, V., Caselli, C., & Gimelli, A. (2021) · European Heart Journal Open · doi:10.1093/ehjopen/oeab004 · Cited by 19
“Patients carrying this specific additional risk pattern could potentially benefit more from treatments targeted to improve metabolic dysregulation(21,22) and to counteract the effects of enhanced systemic inflammation.(23,24) Serum TGs and the TyG index have been associated with the presence and extent of coronary ath…”
BackgroundTargeting Microtubules for the Treatment of Heart Disease
Warner, E. F., Li, Y., & Li, X. (2022) · Circulation Research · doi:10.1161/circresaha.122.319808 · Cited by 22
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“, canakinumab (6) and colchicine (7, 8)] confirmed the direct vasculo-protective effects of primarily targeting inflammation, which may partly explain the residual risk after the normalization of LDL-C.”
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“5 mg once daily) in patients with stable coronary artery disease.(40) Colchicine disrupts tubulin, thereby reducing the migration and replication of inflammatory cells, affecting endothelial function, and inhibiting the NLRP3 inflammasome, but is now also thought to have broader mechanisms of action that are incomplet…”
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“…in High-Risk Patients With Acute Nondisabling Cerebrovascular Events), 12 TST (Treat Stroke to Target) 13 and LoDoCo (Low Dose Colchicine) 14 have addressed 3 main therapeutic targets— residual thrombotic, residual cholesterol, and residual inflammatory risk— in reducing the residual…”
Pham, V., Moroni, A., Gall, E., Benedetti, A., Zivelonghi, C., & Picard, F. A. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12082833 · Cited by 17
“However, canakinumab was not further developed in this setting because of the risk of fatal infections and the high costs, whereas the subsequent LoDoCo2 (second low-dose colchicine) trial and the two-year follow-up of the COPS trial expanded the positive results of colchicine in patients with CCS [68,69].”
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Self-citationNew Insights into Pathophysiology and New Risk Factors for ACS
Nardin, M., Verdoia, M., Laera, N., Cao, D., & Luca, G. D. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12082883 · Cited by 21
“LoDoCo2—RCT Placebo 5522 patients with CCS Reduction of cardiovascular event [93]”
BackgroundAl-Hawary, S. I. S., Jasim, S. A., Romero‐Parra, R. M., Bustani, G. S., Hjazi, A. M., Alghamdi, M., Kareem, A. K., Alwaily, E. R., Zabibah, R. S., Gupta, J., et al. (2023) · Pathology - Research and Practice · doi:10.1016/j.prp.2023.154490 · Cited by 20
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Colchicine in atherosclerotic cardiovascular disease
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“23 In a post hoc analysis of mortality data from LoDoCo2, there is no obvious signal for this increased risk of non-cardiovascular death—rates of death from cancer, end-stage pulmonary disease, infection, dementia and multiorgan failure were individually not significantly different.”
BackgroundResultInfluentialThe Role of Colchicine in Atherosclerotic Cardiovascular Disease
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“Clinical trials evaluating the therapeutic targeting of the inflammatory cytokine interleukin-1β (CANTOS trial) or low-dose therapy with anti-inflammatory Colchicine in patients with chronic coronary disease demonstrated a reduction in the risk of developing adverse cardiovascular events [5,6].”
BackgroundCarotid Atheroinflammation Is Associated With Cerebral Small Vessel Disease Severity
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“Previous reports had shown that colchicine has a certain protective effect on ischemic myocardium, which can reduce the coronary plaque and the area of myocardial infarction in patients with myocardial infarction by inhibiting inflammation response (Nidorf et al., 2019; Nidorf et al., 2020).”
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“However, an increase in non-cardiovascular death was noted in the colchicine group, adding another layer of consideration in its application [48].”
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Reperfused Myocardial Infarction
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Mitsis, A., Sokratous, S., Karmioti, G., Kyriakou, M., Drakomathioulakis, M., Myrianthefs, M. M., Eftychiou, C., Kadoglou, N. P. E., Tzikas, S., Fragakis, N., et al. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14134795 · Cited by 19
“The COLCOT (Colchicine Cardiovascular Outcomes Trial) [84] and LoDoCo2 (Low-Dose Colchicine) [85] studies have compellingly highlighted the significant impact of low-grade inflammation on the prognosis of AMI patients in relation to future cardiovascular events.”
Colchicine reduces atherosclerotic plaque vulnerability in rabbits
Roubille, F., Merlet, N., Busseuil, D., Ferron, M., Shi, Y., Mihalache-Avram, T., Mecteau, M., Brand, G., Rivas, D., Cossette, M., et al. (2021) · Atherosclerosis Plus · doi:10.1016/j.athplu.2021.08.008 · Cited by 18
Colchicine Against SARS-CoV-2 Infection: What is the Evidence?
Drosos, A. A., Pelechas, E., Drossou, V., & Voulgari, P. V. (2022) · Rheumatology and Therapy · doi:10.1007/s40744-022-00425-0 · Cited by 18
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“Furthermore, colchicine has been shown to be effective at preventing major adverse cardiac events after a myocardial infarction(27) and preventing cardiovascular events in patients with recent myocardial infarction(28) and stable coronary disease.(29,30) Future studies should also explore whether systematic attempts t…”
BackgroundTime‐Varying Association of Rheumatoid Arthritis Disease Activity to Subsequent Cardiovascular Risk
Yoshida, K., Harrold, L. R., Middaugh, N., Guan, H., Stryker, S., Karis, E., & Solomon, D. H. (2022) · ACR Open Rheumatology · doi:10.1002/acr2.11432 · Cited by 19
“Anti-in fl ammatory medications initially developed in rheumatology recently started demonstrating CV bene fi ts (eg, canakinu-mab ( 15) and colchicine (16,17)).”
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“LoDoCo2 trial (41) RCT 5522 (2762/2760) CCS 0.”
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Systematic review of colchicine neuromyopathy: Risk factors, duration and resolution
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BackgroundInfluentialTercan, H., van Broekhoven, A., Bahrar, H., Opstal, T. S. J., Cossins, B. C., Rother, N., Rodwell, L., Bekkering, S., Messaoudi, S. E., Riksen, N. P., et al. (2024) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.3394 · Cited by 20
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Therapeutic Implications of NLRP3-Mediated Inflammation in Coronary Artery Disease
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Coronary artery disease: ‘gout’ in the artery?
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“The primary cardiovascular disease endpoints in both COLCOT and LoDoCo2 started to decline very early after the initiation of colchicine therapy, and they were mainly due to a reduction of myocardial infarction and acute ischaemia-driven revascularization.(2,3) Thus, in principle, colchicine administration for coronar…”
BackgroundLow-Dose Colchicine in Coronary Artery Disease ― Systematic Review and Meta-Analysis ―
Abrantes, A., Nogueira-Garcia, B., Alves, M., Passos, D. T., Brito, D. A., Pinto, F. J., & Caldeira, D. (2021) · Circulation Reports · doi:10.1253/circrep.cr-21-0065 · Cited by 18
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Nanomedicine-based strategies for the treatment of vein graft disease
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“More-over, the COLCOT trial 148 and the LoDoCo2 trial 149 have led to the FDA approval of the anti-inflammatory drug colchicine for the treatment of atherosclerotic diseases.”
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“15 In brief, the LoDoCo2 Trial randomised 5522 patients with chronic coronary disease to receive colchicine 0.5 mg daily or matching placebo on a background of optimal medical therapy.”
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Anti-inflammatory Treatment and Cardiovascular Outcomes: Results of Clinical Trials
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The Spectrum of B Cell Functions in Atherosclerotic Cardiovascular Disease
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“The controlled double-blind clinical trials CANTOS (20), COLCOT (21), and LoDoCo2 (22) have demonstrated the therapeutic value of immunomodulation in secondary prevention of ASCVD.”
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Self-citationCharacteristics of Premature Myocardial Infarction Among Women With Prior Adverse Pregnancy Outcomes
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Colchicine protects against the development of experimental abdominal aortic aneurysm
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“Studies showed that colchicine treatment could reduce the risk of cardiovascular events including myocardial infarction, chronic coronary disease, recurrent pericarditis and atrial fibrillation [10,12,15–17].”
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“…five large randomized clinical trials, including the CANTOS trial, demonstrated that baseline NLR modestly correlated with hsCRP, interleukin (IL)-6 and fibrinogen, and it could consistently and independently predict cardiovascular events and death after adjusting the effect of hsCRP. 9 These…”
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BackgroundInfluentialLipid Disorders Management Strategies (2024) in Prediabetic and Diabetic Patients
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BackgroundUpdate on the Role of Colchicine in Cardiovascular Disease
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BackgroundUndertreatment or Overtreatment With Statins: Where Are We?
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Metadata
- Authors
- Nidorf, S. M., Fiolet, A. T. L., Mosterd, A., Eikelboom, J. W., Schut, A., Opstal, T. S. J., The, S. H. K., Xu, X.-F., Ireland, M. A., Lenderink, T., Latchem, D., Hoogslag, P., Jerzewski, A., Nierop, P., Whelan, A., Hendriks, R., Swart, H., Schaap, J., Kuijper, A. F. M., van Hessen, M. W. J., Saklani, P., Tan, I., Thompson, A. G., Morton, A., Judkins, C., Bax, W. A., Dirksen, M., Alings, M., Hankey, G. J., Budgeon, C. A., Tijssen, J. G. P., Cornel, J. H., & Thompson, P. L.
- Affiliations
- Sir Charles Gairdner Hospital (AU)
- Gelre Hospitals (NL)
- From GenesisCare Western Australia (S.M.N., X.-F.X., M.A.I., D.L., A.W., R.H., P.S., I.T., A.G.T., A. Morton, P.L.T.), the Heart and Vascular Research Institute (S.M.N., P.L.T.) and the Department of Neurology (G.J.H.), Sir Charles Gairdner Hospital, and the Faculty of Health and Medical Sciences (G.J.H., P.L.T.) and the School of Population and Global Health (C.A.B.), University of Western Australia, Perth, the Department of Cardiology, Fiona Stanley Hospital, Murdoch, WA (C.J.), and the Harry...
- The University of Western Australia (AU)
- Harry Perkins Institute of Medical Research (AU)
- ORCID
- Nidorf, Stefan M.
- Fiolet, Aernoud T.L.
- Mosterd, Arend
- Eikelboom, John W.
- Schut, Astrid
- Opstal, Tjerk S.J.
- Lenderink, Timo
- Schaap, Jeroen
- Kuijper, Aaf F.M.
- Thompson, Angus G.
- Morton, Allison
- Bax, Willem A.
- Dirksen, Maurits
- Alings, Marco
- Hankey, Graeme J.
- Budgeon, Charley A.
- Tijssen, Jan G.P.
- Cornel, Jan H.
- Thompson, Peter L.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2020-11-05
- Volume
- 383
- Issue
- 19
- Pages
- 1838-1847
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W3081761942
- Cited by
- 2,299
- References
- 37
- Citations by year
- 2026: 446 · 2025: 455 · 2024: 388 · 2023: 345 · 2022: 298 · 2021: 311 · 2020: 55
- FWCI
- 155.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- Pure Amsterdam UMC (acceptedVersion, cc-by)
- Radboud Repository (Radboud University) (submittedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- the National Health Medical Research Council of Australia (NHMRC project grant APP1088455)
- the Withering Foundation the Netherlands
- the Netherlands Organization for Health Research and Development (Grantnr. 848015014)
- the Netherlands Heart Foundation
- Aspen, Australia
- Teva, Haarlem, Disphar, Baarn and Tiofarma, Oud-Beijerland
- Research Advisory Committee of Sir Charles Gairdner Hospital and Osborne ParkGroup and Charlies Foundation for Research
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- colchicine, stable coronary artery disease, anti-inflammatory therapy, cardiovascular events, myocardial infarction, ischemic stroke, cardiovascular mortality, coronary revascularization, non-cardiovascular mortality, antiplatelet therapy, statins, coronary artery disease, secondary prevention, cardiovascular risk reduction, cardiovascular risk stratification
- MeSH terms
- Aged, Anti-Inflammatory Agents, Cardiovascular Diseases, Chronic Disease, Colchicine, Coronary Disease, Double-Blind Method, Female, Follow-Up Studies, Humans, Male, Middle Aged, Incidence, Proportional Hazards Models, Intention to Treat Analysis
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