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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.”
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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.”
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“Several trials implementing pharmaceutical anti-inflammatory therapies have yielded promising results, including canakinumab targeting interleukin (IL)-1 β , 1 colchicine targeting microtubules, 2,3 and ziltivekimab targeting the IL-6 ligand.”
BackgroundTargeting the Inflammasome in Cardiovascular Disease
Olsen, M. B., Gregersen, I., Sandanger, Ø., Yang, K., Sokolova, M., Halvorsen, B. L., Gullestad, L. L., Broch, K., Aukrust, P., & Louwe, M. C. (2021) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2021.08.006 · Cited by 178
Shared inflammatory pathways of rheumatoid arthritis and atherosclerotic cardiovascular disease
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Inflammation in heart failure: pathophysiology and therapeutic strategies
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“Specifically, colchicine has been clearly demonstrated in two large, randomized trials (COLCOT and LoDoCo2) to be beneficial in reducing the risk of atherothrombotic CV events in patients with coronary artery disease [112, 113].”
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C-Reactive Protein and Risk of Incident Heart Failure in Patients With Cardiovascular Disease
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Self-citationAnti-inflammatory therapy for COVID-19 infection: the case for colchicine
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“The LoDoCo2 study in patients in the chronic phase of coronary artery disease showed similar efficacy [42].”
BackgroundProteomics and lipidomics in atherosclerotic cardiovascular disease risk prediction
Nurmohamed, N. S., Kraaijenhof, J. M., Mayr, M., Nicholls, S. J., Köenig, W., Catapano, A. L., & Stroes, E. S. G. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad161 · Cited by 156
Autoimmune diseases and atherosclerotic cardiovascular disease
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Ridker, P. M., Lei, L., Louie, M. J., Haddad, T. M., Nicholls, S. J., Lincoff, A. M., Libby, P., Nissen, S. E., & on behalf of the CLEAR Outcomes Investigators (2023) · Circulation · doi:10.1161/circulationaha.123.066213 · Cited by 162
Targeted proteomics improves cardiovascular risk prediction in secondary prevention
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Signaling pathways in macrophages: molecular mechanisms and therapeutic targets
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Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients
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Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review
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Low-Grade Chronic Inflammation: a Shared Mechanism for Chronic Diseases
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Common Pathophysiology in Cancer, Atrial Fibrillation, Atherosclerosis, and Thrombosis
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“Additionally, there was a reduction in new onset or first recurrence of AF, though it did not reach statistical significance (28).”
BackgroundUnderstanding the molecular mechanisms of statin pleiotropic effects
German, C. A., & Liao, J. K. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03492-6 · Cited by 160
“2017), Low-Dose Colchicine (LoDoCo) trial (Nidorf et al. 2020), and Colchicine Cardiovascular Outcomes (COLCOT) Trial (Tardif et al.”
BackgroundColchicine in Cardiovascular Disease: In-Depth Review.
Deftereos, S. G., Beerkens, F., Shah, B., Γιαννόπουλος, Γ., Vrachatis, D. A., Giotaki, S. G., Siasos, G., Nicolas, J., Arnott, C. G., Patel, S. V., et al. (2022) · PubMed · doi:10.1161/circulationaha.121.056171 · Cited by 142
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Challenges and advances in the management of inflammation in atherosclerosis
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“This trial enrolled 5,522 participants and, after a median follow-up of 28.6 months, showed that the colchicine group had a significantly lower rate of cardiovascular events compared to the placebo group [152].”
InfluentialTargeting IL-1β in the Treatment of Atherosclerosis
Mai, W., & Liao, Y. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.589654 · Cited by 147
“Recent research show evidence that colchicine may reduce the cardiovascular risk in patients with chronic coronary disease (75), but the evidence is weak and the side effects is significant, especially in gastrointestinal system.”
BackgroundEndothelial shear stress signal transduction and atherogenesis: From mechanisms to therapeutics
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Role of the CCL2-CCR2 axis in cardiovascular disease: Pathogenesis and clinical implications
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“HEB was funded by the Novo Nordisk Foundation (grant numbers NNF14OC0013337, NNF15OC0016674), The Danish Council for Strategic Research (11-108354), and Trygfonden (109624).”
Myocardial infarction drives trained immunity of monocytes, accelerating atherosclerosis
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Self-citationTrained immunity in atherosclerotic cardiovascular disease
Riksen, N. P., Bekkering, S., Mulder, W. J. M., & Netea, M. G. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00894-y · Cited by 134
“Chronic treatment with broad anti-inflammatory drugs can lower the risk of ASCVD but at the cost of increased infection-related complications and with a considerable remaining residual risk 1,2 .”
BackgroundImmune cell profiling in atherosclerosis: role in research and precision medicine
Fernandez, D. M., & Giannarelli, C. (2021) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00589-2 · Cited by 126
Diagnosis and Management of Stable Angina
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Animal Models of Atherosclerosis–Supportive Notes and Tricks of the Trade
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World Heart Federation Roadmap for Secondary Prevention of Cardiovascular Disease: 2023 Update
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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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