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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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“Several clinical anti-inflammatory trials such as CANTOS[7],CIRT[8]andLoDoCo2[9,10]gavepromising but still inconclusive findings.”
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“Current CVD prevention strategies are based on lifestyle interventions in combination with medical treatment of conventional risk factors such as dyslipidaemia and hypertension [3].”
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Daub, S., Lutgens, E., Münzel, T. F., & Daiber, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228533 · Cited by 56
“It is also well established that cardiovascular prognosis can be improved by targeted anti-inflammatory therapy in patients with rheumatoid arthritis (IL-6, TNF-α and IL-17A cascades) [25,26], psoriasis (IL-17/IL-23 axis) [27–29] and systemic lupus erythematosus (IL-17A signaling) [30] and other markers of inflammatio…”
BackgroundBroeders, W., Bekkering, S., Messaoudi, S. E., Joosten, L. A. B., van Royen, N., & Riksen, N. P. (2022) · Basic Research in Cardiology · doi:10.1007/s00395-022-00935-6 · Cited by 57
“This beneficial effect was confirmed in two large RCTs in patients after recent myocardial infarction [148], or with chronic coronary disease [105].”
ResultInnate immune memory in cardiometabolic disease
Bahrar, H., Bekkering, S., Stienstra, R., Netea, M. G., & Riksen, N. P. (2023) · Cardiovascular Research · doi:10.1093/cvr/cvad030 · Cited by 53
Role of Inflammation in Coronary Epicardial and Microvascular Dysfunction
Godo, S., TAKAHASHI, J. C., Yasuda, S., & Shimokawa, H. (2021) · European Cardiology Review · doi:10.15420/ecr.2020.47 · Cited by 54
O’Fee, K., Deych, E., Ciani, O., & Brown, D. (2021) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2021.5726 · Cited by 54
Kaura, A., Hartley, A., Panoulas, V. F., Glampson, B., Shah, A. S. V., Davies, J., Mulla, A., Woods, K., Omigie, J., Shah, A. D., et al. (2022) · PLoS Medicine · doi:10.1371/journal.pmed.1003911 · Cited by 57
“More recent supportive evidence of targeting inflammation in CVD has been published, with the Colchicine Cardiovascular Outcomes Trial (COLCOT) [18] and the Low Dose Colchicine (LoDoCo2) for secondary prevention of CVD trial [19] reporting significant reductions in CV end points using colchicine, an immunomodulatory a…”
BackgroundResultZhang, J., Jia, J., Lai, R., Wang, X., Chen, X., Tian, W., Liu, Q., Li, J., Ju, J., & Xu, H. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2022.1044329 · Cited by 53
Bonfioli, G. B., Rodella, L., Metra, M., & Vizzardi, E. (2024) · Heart Failure Reviews · doi:10.1007/s10741-024-10450-6 · Cited by 58
Diabetes-Driven Atherosclerosis: Updated Mechanistic Insights and Novel Therapeutic Strategies
Karakasis, P., Theofilis, P., Patoulias, D., Vlachakis, P. K., Antoniadis, A. P., & Fragakis, N. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26052196 · Cited by 63
“The COLCOT trial [161] demonstrated the efficacy of colchicine in reducing cardiovascular events in post-myocardial infarction patients, while the LoDoCo2 trial [162] confirmed its benefits in patients with chronic stable coronary artery disease.”
Andreis, A., Imazio, M., Avondo, S., Casula, M., Paneva, E., Piroli, F., & Ferrari, G. M. D. (2021) · Journal of Cardiovascular Medicine · doi:10.2459/jcm.0000000000001157 · Cited by 54
Colchicine in ischemic heart disease: the good, the bad and the ugly
D’Amario, D., Cappetta, D., Cappannoli, L., Princi, G., Migliaro, S., Diana, G., Chouchane, K., Borovac, J. A., Restivo, A., Arcudi, A., et al. (2021) · Clinical Research in Cardiology · doi:10.1007/s00392-021-01828-9 · Cited by 56
“Similar results emerged in the LoDoCo2 trial [45], in which investigators state in the discussion of their manuscript that the observed non-significant incidence of non-CV death in the colchicine arm could have been due to chance, although an obtained hazard ratio of 1.”
BackgroundResultYuan, D., Jiang, P. X., Zhu, P., Jia, S., Zhang, C., Liu, Y., Liu, R., Xu, J., Tang, X., Zhao, X., et al. (2021) · Cardiovascular Diabetology · doi:10.1186/s12933-021-01335-1 · Cited by 56
Modern Concepts in Cardiovascular Disease: Inflamm-Aging
Puspitasari, Y. M., Ministrini, S., Schwarz, L., Karch, C., Liberale, L., & Camici, G. G. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.882211 · Cited by 57
Chronic inflammation and vascular cell plasticity in atherosclerosis
Lin, A., Miano, J. M., Fisher, E. A. A., & Misra, A. (2024) · Nature Cardiovascular Research · doi:10.1038/s44161-024-00569-y · Cited by 56
Freeman, A. M., Raman, S. V., Aggarwal, M., Maron, D. J., Bhatt, D. L., Parwani, P. J., Osborne, J., Earls, J. P., Min, J. K., Bax, J. J., et al. (2022) · The American Journal of Medicine · doi:10.1016/j.amjmed.2022.10.021 · Cited by 53
Monomeric C-Reactive Protein in Atherosclerotic Cardiovascular Disease: Advances and Perspectives
Melnikov, I., Kozlov, S. G., Saburova, O., Avtaeva, Y., Guria, K. G., & Ахнафович, Г. З. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032079 · Cited by 56
Colchicine in acutely decompensated heart failure: the COLICA trial
Pascual-Figal, D. A., Núñez, J. E., Pérez-Martínez, M. T., González‐Juanatey, J. R., Urquía, M. T., Llàcer, P., Delgado, J. F., Villar, S., Mirabet, S., Aimo, A., et al. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehae538 · Cited by 51
The Interplay Between Immunity, Inflammation and Endothelial Dysfunction
Chee, Y. J., Dalan, R., & Cheung, C. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26041708 · Cited by 62
“In another study, cardiovascular events were reduced by 31% among individuals with pre-existing coronary artery disease after approximately 29 months of low-dose colchicine [242].”
InfluentialTargeting residual inflammatory risk: The next frontier for atherosclerosis treatment and prevention
Ridker, P. M. (2023) · Vascular Pharmacology · doi:10.1016/j.vph.2023.107238 · Cited by 51
Detection of Vulnerable Coronary Plaques Using Invasive and Non-Invasive Imaging Modalities
van Veelen, A., van der Sangen, N. M. R., Delewi, R., Beijk, M. A. M., Henriques, J. P. S., & Claessen, B. E. P. M. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11051361 · Cited by 52
“studied in the LoDoCo2 trial and COLCOT trial [157,158], and the interleukin-1-beta antagonist canakinumab, studied in the CANTOS trial [159], are able to reduce the risk for cardiac events.”
BackgroundGirard, D., & Vandiedonck, C. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.991716 · Cited by 55
“The second randomized clinical trial involved colchicine, a known anti-inflammatory natural molecule that inhibits cytoskeleton microtubule formation, was used in the LoDoCo2 phase III clinical trial to treat patients with advanced CAD (49).”
MethodBenz, A. P., Amit, G., Connolly, S. J., Singh, J., Acosta‐Vélez, J. G., Conen, D., Deif, B., Divakaramenon, S., McIntyre, W. F., Mtwesi, V., et al. (2023) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.123.012387 · Cited by 54
“9,10 We evaluated a 10-day treatment with colchicine in patients undergoing catheter ablation for AF in a randomized, double-blind, placebo-controlled clinical trial.”
MethodCanonical and non-canonical roles of complement in atherosclerosis
Maffia, P., Mauro, C., Case, A. G., & Kemper, C. (2024) · Nature Reviews Cardiology · doi:10.1038/s41569-024-01016-y · Cited by 53
“Anti-inflammatory therapies, such as canakinumab 187 (a monoclonal antibody to IL-1β) and colchicine 188,189 , have been shown to reduce the risk of recurrent cardiovascular events in patients with previous MI.”
Controversies and practical management of patients with gout and chronic kidney disease
Johnson, R. J., Mandell, B. F., Schlesinger, N., Mount, D. B., Botson, J. K., Abdellatif, A. A., Rhoades, R., & Singh, J. A. (2024) · Kidney International · doi:10.1016/j.kint.2024.05.033 · Cited by 50
Clinical Updates in Coronary Artery Disease: A Comprehensive Review
Bottardi, A., Prado, G. F. A., Lunardi, M., Fezzi, S., Pesarini, G., Tavella, D., Scarsini, R., & Ribichini, F. L. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13164600 · Cited by 60
“Regarding CCS, in the Low-dose Colchicine trial-2 (LoDoCo2) trial, patients who received colchicine (0,5 mg once daily) presented fewer CV adverse events compared to placebo (HR, 0.69; 95% CI, 0.57 to 0.83; p < 0.001) [165].”
BackgroundInfluentialCarotid Plaque Inflammation Imaged by PET and Prediction of Recurrent Stroke at 5 Years
McCabe, J. J., Camps‐Renom, P., Giannotti, N., McNulty, J. P., Coveney, S. A., Murphy, S., Barry, M. C., Harbison, J. A., Cronin, S., Williams, D. J., et al. (2021) · Neurology · doi:10.1212/wnl.0000000000012909 · Cited by 49
Inflammatory Links Between Hypertriglyceridemia and Atherogenesis
Peng, X., & Wu, H. (2022) · Current Atherosclerosis Reports · doi:10.1007/s11883-022-01006-w · Cited by 51
Innate immune signaling and immunothrombosis: New insights and therapeutic opportunities
Ryan, T. A. J., & O'Neill, L. A. J. (2022) · European Journal of Immunology · doi:10.1002/eji.202149410 · Cited by 53
German, C. A., Baum, S. J., Ferdinand, K. C., Gulati, M., Polonsky, T. S., Toth, P. P., & Shapiro, M. D. (2022) · American Journal of Preventive Cardiology · doi:10.1016/j.ajpc.2022.100432 · Cited by 55
Fidler, T. P., Dunbar, A. J., Kim, E., Hardaway, B., Pauli, J., Xue, C., Abramowicz, S., Xiao, T., O’Connor, K., Sachs, N., et al. (2024) · Nature Cardiovascular Research · doi:10.1038/s44161-023-00405-9 · Cited by 51
Platelet signaling in immune landscape: comprehensive mechanism and clinical therapy
Yan, M., Wang, Z., Qiu, Z., Cui, Y., & Xiang, Q. (2024) · Biomarker Research · doi:10.1186/s40364-024-00700-y · Cited by 49
Coveney, S. A., Murphy, S., Belton, O., Cassidy, T., Crowe, M., Dolan, E., de Gaetano, M., Harbison, J. A., Horgan, G. W., Marnane, M., et al. (2021) · International Journal of Stroke · doi:10.1177/1747493021995595 · Cited by 46
Georgakis, M. K., Malik, R., Burgess, S., & Dichgans, M. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.121.023277 · Cited by 45
Hypotension as a marker or mediator of perioperative organ injury: a narrative review
Ackland, G. L., & Abbott, T. E. F. (2022) · British Journal of Anaesthesia · doi:10.1016/j.bja.2022.01.012 · Cited by 53
Xiong, J., Li, Z., Tang, H., Duan, Y., Ban, X., Xu, K., Guo, Y., & Tu, Y. (2023) · BMC Biology · doi:10.1186/s12915-023-01540-2 · Cited by 50
“However, the negative results of the Cardiovascular Inflammation Reduction Trial and the increased risks of infection associated with systemic anti-inflammatory treatments (as observed in the Canakinumab Antiinflammatory Thrombosis Outcomes Study [CANTOS] and Colchicine Cardiovascular Outcomes Trial [COLCOT]) suggest…”
ResultKynurenic Acid/AhR Signaling at the Junction of Inflammation and Cardiovascular Diseases
Grishanova, A. Y., & Perepechaeva, M. L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25136933 · Cited by 53
“Modern methods of prevention of CVDs are based on compliance with a healthy lifestyle in combination with pharmacotherapy of traditional risk factors related to dyslipidemia, obesity, and hypertension [4].”
MethodTherapeutic innovation in drug repurposing: Challenges and opportunities
Recino, A., Rayner, M., Rohn, J. L., Pasqua, O. E. D., Recino, A., Rayner, M. L. D., Rohn, J. L., Carter, B., Cupani, A., Dahlmann-Noor, A. H., et al. (2025) · Drug Discovery Today · doi:10.1016/j.drudis.2025.104390 · Cited by 48
The Intriguing Role of TLR Accessory Molecules in Cardiovascular Health and Disease
Bezhaeva, T., Karper, J. C., Quax, P. H. A., & de Vries, M. R. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.820962 · Cited by 48
“In CVD, inflammation plays an important role in both disease progression and resolution as has been showing elegantly the successes of the CANTOS trial (17) and the COLCOT and LoDoCo2 trials (182, 183).”
BackgroundPopescu, D., Rezuş, E., Bădescu, M. C., Dima, N., Isac, P. N. S., Dragoi, I.-T., & Rezuș, C. (2023) · Life · doi:10.3390/life13020319 · Cited by 50
“At the end of follow‐up, patients who received colchicine had a lower risk of cardiovascular events compared to the placebo group [78].”
BackgroundSchnabel, R. B., Hasenfuß, G., Buchmann, S. J., Kahl, K. G., Aeschbacher, S., Osswald, S., & Angermann, C. E. (2021) · Herz · doi:10.1007/s00059-021-05022-5 · Cited by 50
P2Y12 Inhibitor Monotherapy Combined With Colchicine Following PCI in ACS Patients
Lee, S., Jeong, Y., Yun, K. H., Cho, J. Y., Gorog, D. A., Angiolillo, D. J., Kim, J. W., & Jang, Y. (2023) · JACC: Cardiovascular Interventions · doi:10.1016/j.jcin.2023.05.035 · Cited by 48
“Stent thrombosis was classified into definite, probable, or possible according to the Academic Research Consortium definition (17).”
Fan, L., Liu, J., Hu, W., Chen, Z., Lan, J., Zhang, T., Zhang, Y., Wu, X., Zhong, Z., Zhang, D., et al. (2024) · Cell Research · doi:10.1038/s41422-024-00945-0 · Cited by 47
“13 For example, the Canakinumab Anti-in fl ammatory Thrombosis Outcome Study (CANTOS) exploited a combination of lipid-lowering and anti-in fl ammatory agents, such as anti-interleukin (IL)-1 β monoclonal antibody (mAb), which neutralizes the NLRP3/IL-1 β pathway and synthesis of pro-in fl ammatory…”
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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