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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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BackgroundColchicine Blocks Tubulin Heterodimer Recycling by Tubulin Cofactors TBCA, TBCB, and TBCE
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“5 mg of colchicine per day reduced the risk of major cardiovascular events by 31% in patients with chronic coronary heart disease (Fischer, 2021).”
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“10 11 The ongoing CONVINCE (Colchicine for Prevention of Vascular Inflammation in Non-cardio Embolic Stroke) study evaluates the effect of low-dose colchicine in reducing the rate of recurrent stroke in patients who had a stroke (URL: http://www. clinicaltrials. gov. NCT02898610).”
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Sandner, S. E., Antoniades, C. A., Caliskan, E., Czerny, M., Dayan, V., Fremes, S. E., Glineur, D., Lawton, J. S., Thielmann, M., & Gaudino, M. F. L. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehae654 · Cited by 30
Estimating inflammatory risk in atherosclerotic cardiovascular disease: plaque over plasma?
Annink, M. E., Kraaijenhof, J. M., Beverloo, C. Y. Y., Oostveen, R. F., Verberne, H. J., Stroes, E. S. G., & Nurmohamed, N. S. (2024) · European Heart Journal - Cardiovascular Imaging · doi:10.1093/ehjci/jeae314 · Cited by 29
Bosco, G., Barbagallo, F. D. G., Marco, M. D., Scilletta, S., Miano, N., Capuccio, S., Musmeci, M., Mauro, S. D., Filippello, A., Scamporrino, A., et al. (2024) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2024.12.002 · Cited by 28
Inflammation as a determinant of healing response after coronary stent implantation
Ochijewicz, D., Tomaniak, M., Opolski, G., & Kochman, J. (2021) · International journal of cardiac imaging · doi:10.1007/s10554-020-02073-3 · Cited by 32
“In patients within 30 days after myocardial infarction and in patients with chronic coronary syndrome administration of colchicine significantly decreased ischemic cardiovascular events in comparison to placebo [87, 88].”
BackgroundBenz, A. P., Aeschbacher, S., Krisai, P., Moschovitis, G., Blum, S., Meyre, P. B., Blum, M. R., Rodondi, N., Valentino, M. D., Kobza, R., et al. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.120.019168 · Cited by 28
“– 21 Of note, a post hoc analysis from 1 of these trials showed a dose-dependent reduction in heart failure hospitalization related to ischemic heart disease in patients randomized to canakinumab.”
Ma, J., Liu, X., Qiao, L., Meng, L., Xu, X., Xue, F., Cheng, C., Han, Z., Lu, Y., Zhang, W., et al. (2021) · Circulation Cardiovascular Interventions · doi:10.1161/circinterventions.121.010764 · Cited by 28
Self-citationRisk of cardiovascular events in patients having had acute calcium pyrophosphate crystal arthritis
Tedeschi, S. K., Huang, W., Yoshida, K., & Solomon, D. H. (2022) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2022-222387 · Cited by 28
Cholesterol trafficking, lysosomal function, and atherosclerosis
Skeyni, A., Pradignac, A., Matz, R. L., Terrand, J., & Boucher, P. (2023) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00415.2023 · Cited by 30
Inhibiting Interleukin-6 to Reduce Cardiovascular Event Rates
Ridker, P. M. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.02.060 · Cited by 28
Emerging role of exosomes in vascular diseases
Ren, Y., & Zhang, H. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1090909 · Cited by 29
“Recent clinical trials have shown that targeting inflammation can reduce cardiovascular events even in individuals who have been treated with a full panel of effective standard therapies, with relevant anti-inflammatory drugs including canakinumab and colchicine (110, 111).”
BackgroundUrbanowicz, T. K., Michalak, M., Komosa, A., Olasińska‐Wiśniewska, A., Filipiak, K. J., Tykarski, A., & Jemielity, M. (2023) · Cardiology Journal · doi:10.5603/cj.a2023.0033 · Cited by 27
Figueiredo, C. S., Roseira, E. S., Viana, T. T., Silveira, M. A. D., de Melo, R. M. V., Fernandez, M. G., Lemos, L. M. G., & Passos, L. C. S. (2023) · Pharmaceuticals · doi:10.3390/ph16091242 · Cited by 30
“The intervention was associated with a 2.8% absolute reduction in the primary endpoint when compared to placebo (HR 0.69, 95% CI 0.57–0.83, p 0.001) [25].”
InfluentialNazari, I. S., & Feinstein, M. J. (2024) · Clinical Microbiology Reviews · doi:10.1128/cmr.00098-22 · Cited by 29
“…the Colchicine Cardiovascular Outcomes Trial (COLCOT) and the second low-dose colchicine trial (LODOCO2) found that 0.5 mg of colchicine daily significantly decreased the risk of cardiovascular events in patients with recent MI and patients with chronic coronary disease, respectively (195, 196).”
BackgroundInfluentialKhan, D., Zhou, H., You, J., Kaiser, V. A., Khajuria, R. K., & Muhammad, S. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01594-x · Cited by 27
Moneva-Sakelarieva, M. G., Kobakova, Y. A., Konstantinov, S., Momekov, G., Ivanova, S., Atanasova, V. P., Chaneva, M. S., Tododrov, R., Bashev, N. Z., & Atanasov, P. Y. (2025) · Pharmacia · doi:10.3897/pharmacia.72.e146759 · Cited by 30
“In addition, clinical trials have shown that the anti-inflammatory agent colchicine reduces the risk of cardiovascular events in patients with recent myocardial infarction or coronary artery disease (Nidorf et al. 2020).”
Whelton, S. P., Berning, P., Blumenthal, R. S., Marshall, C. H., Martin, S. S., Mortensen, M. B., Blaha, M. J., & Dzaye, O. D. A. (2021) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2021.02.003 · Cited by 27
Anti-inflammatory Therapies for Coronary Heart Disease: A Systematic Review and Meta-Analysis
Wang, H., Jiang, M., Li, X., Zhao, Y., Shao, J., Liu, Z., Lin, L., Xu, Q., Wang, L., Lu, X.-C., et al. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.726341 · Cited by 27
“As anticipated, both the CANTOS trial and the LoDoCo2 trial confirmed the beneficial effects of anti-inflammatory therapy with canakinumab and colchicine (7, 9).”
BackgroundResultKrzywik, J., Nasulewicz‐Goldeman, A., Mozga, W., Wietrzyk, J., & Huczyński, A. (2021) · ACS Omega · doi:10.1021/acsomega.1c03948 · Cited by 27
Komatsu, S., Yutani, C., Takahashi, S., Takewa, M., Ohara, T., Hirayama, A., & Kodama, K. (2022) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2022.03.010 · Cited by 27
Niu, Y., Bai, N., Ma, Y., Zhong, P.-Y., Shang, Y.-S., & Wang, Z.-L. (2022) · BMC Cardiovascular Disorders · doi:10.1186/s12872-022-02525-9 · Cited by 26
“LoDoCo2 [9] 2020 RCT CCS 5522 Colchicine (n = 2762) VS Placebo (n = 2760) 28.”
Tackling inflammation in atherosclerosis: Are we there yet and what lies beyond?
Bhattacharya, P., Kanagasooriyan, R., & Subramanian, M. (2022) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2022.102283 · Cited by 31
Chronic rheumatologic disorders and cardiovascular disease risk in women
Mehta, P. K., Levit, R. D., Wood, M. J., Aggarwal, N. R., O’Donoghue, M. L., Lim, S. S., Lindley, K., Gaignard, S. M., Quesada, O., Vatsa, N., et al. (2023) · American Heart Journal Plus Cardiology Research and Practice · doi:10.1016/j.ahjo.2023.100267 · Cited by 29
“In patients with stable CAD, colchicine was effective in reducing cardiovascular events [97].”
BackgroundColchicine for Secondary Cardiovascular Prevention in Coronary Disease
Roubille, F., & Tardif, J. (2020) · Circulation · doi:10.1161/circulationaha.120.051240 · Cited by 27
Leukocyte–endothelial interaction in CKD
Sarakpi, T., Mesic, A., & Speer, T. (2023) · Clinical Kidney Journal · doi:10.1093/ckj/sfad135 · Cited by 27
“Furthermore, colchicine was associated with an increased incidence of death from non-cardiovascular causes in the LoDoCo2 trial without reaching statistical significance [175].”
BackgroundInfluentialDapansutrile Ameliorates Atrial Inflammation and Vulnerability to Atrial Fibrillation in HFpEF Rats
Yang, H., Zhu, J., Fu, H., & Shuai, W. (2023) · Heart Lung and Circulation · doi:10.1016/j.hlc.2023.09.017 · Cited by 26
Atherosclerosis antigens as targets for immunotherapy
Raposo-Gutiérrez, I., Rodríguez-Ronchel, A., & Ramiro, A. R. (2023) · Nature Cardiovascular Research · doi:10.1038/s44161-023-00376-x · Cited by 26
“The IgH and IgL chains include a variable region at anti-inflammatory treatment with colchicine led to a significantly lower risk of ischemic cardiovascular events among patients with a recent myocardial infarction 14,15 .”
BackgroundKurt, B., Rex, K., Reugels, M., Fordyce, C. B., Fudim, M., Sharma, A., Berger, M., Marx, N., Marx-Schütt, K., & Kahles, F. (2025) · Current Heart Failure Reports · doi:10.1007/s11897-025-00710-3 · Cited by 30
“…the “Low-Dose Colchicine 2” (LoDoCo2) trial, highlighted the risk reduction for cardiovascular events achieved by targeting the nucleotide-binding domain-like receptor pro - tein 3 (NLRP3) inflammasome in ASCVD, emphasizing the therapeutic potential of anti-inflammatory strategies in CVD [14].”
Single cell analyses to understand the immune continuum in atherosclerosis
Hill, C. A., Fernandez, D. M., & Giannarelli, C. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.04.003 · Cited by 28
Montarello, N. J., Singh, K., Sinhal, A. R., Wong, D. T. L., Alcock, R. F., Rajendran, S., Dautov, R. F., Barlis, P., Patel, S., Nidorf, S. M., et al. (2021) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-021-07240-9 · Cited by 26
Self-citationTargeting cytokines and immune checkpoints in atherosclerosis with monoclonal antibodies
Lutgens, E., Joffre, J., van Os, B. W., & Ait‐Oufella, H. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.09.024 · Cited by 26
Inflammatory Biomarkers in Coronary Artery Ectasia: A Systematic Review and Meta-Analysis
Vrachatis, D. A., Papathanasiou, K. A., Kazantzis, D., Sanz‐Sánchez, J., Giotaki, S. G., Raisakis, K., Kaoukis, A., Kossyvakis, C., Deftereos, G., Reimers, B., et al. (2022) · Diagnostics · doi:10.3390/diagnostics12051026 · Cited by 26
“Lately, anti-inflammatory treatments in cardiovascular disease have Diagnostics 2022, 12, 1026 8 of 12 been focused on, showing benefit in large RCTs [75,76].”
BackgroundDimosiari, A., Patoulias, D., Kitas, G. D., & Dimitroulas, T. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12041302 · Cited by 28
“The only “anti-inflammatory” treatment that has been shown to provide significant cardiovascular benefits, mainly in the field of secondary prevention of CVD, is colchicine [80,81], while others, such as low-dose methotrexate, have completely failed in this direction [82].”
BackgroundNew Concepts on the Pathophysiology of Acute Coronary Syndrome
Yuan, D., Chu, J., Qian, J., Lin, H., Zhu, G., Chen, F., & Liu, X. (2023) · Reviews in Cardiovascular Medicine · doi:10.31083/j.rcm2404112 · Cited by 26
“Therefore, when plaque rupture is accompanied by systemic inflammation, anti-inflammatory treatments such as colchicine [18], methotrexate, and IL-1 β neutralizing antibodies [19] may be of benefit to ACS patients [20].”
BackgroundKumrić, M., Urlić, H., Božić, J., Vilović, M., Kurir, T. T., Glavaš, D., Miric, D., Zanchi, J., Bradarić, A., Lozo, M., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098062 · Cited by 27
“The Low-Dose Colchicine 2 (LoDoCo2) trial yielded consistent results in patients with chronic coronary disease [119].”
ResultThe effect of immunomodulatory drugs on aortic stenosis: a Mendelian randomisation analysis
Ciofani, J. L., Han, D., Nazarzadeh, M., Allahwala, U. K., Maria, G. L. D., BANNING, A. P., Bhindi, R., & Rahimi, K. (2023) · Scientific Reports · doi:10.1038/s41598-023-44387-x · Cited by 27
“…rates of further cardiovascular events in patients treated with colchicine compared to placebo, and the Low-Dose Colchicine trial in 5522 patients with chronic coronary disease similarly demonstrated reduced cardiovascular event rates in patients treated with colchicine compared to placebo 18,19 .”
BackgroundInflammation-Related Risk Loci in Genome-Wide Association Studies of Coronary Artery Disease
Mauersberger, C., Schunkert, H., & Sager, H. B. (2021) · Cells · doi:10.3390/cells10020440 · Cited by 27
“Soon thereafter, low dose colchicine, another drug with anti-inflammatory properties, showed a promising effect in patients after myocardial infarction and recently also in patients with chronic coronary syndrome [2,3].”
BackgroundImmunomodulation of Myocardial Fibrosis
Sikking, M. A., Stroeks, S. L. V. M., Marelli‐Berg, F. M., Heymans, S. R. B., Ludewig, B., & Verdonschot, J. A. J. (2023) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2023.03.015 · Cited by 28
Robinson, K. A., Akbar, N., Baidžajevas, K., & Choudhury, R. P. (2023) · The FASEB Journal · doi:10.1096/fj.202301078r · Cited by 26
“In addition to drugs that target inflammatory cytokines, drugs that inhibit the NLRP3 inflammasome such as colchicine led to a significantly lower risk of cardiovascular events in patients with recent myocardial infarction 80 (COLCOT) or chronic coronary disease 81 (Lo-DoCo2).”
BackgroundJansen, S. J., de Borst, G. J., Hinchliffe, R. J., & Teraa, M. (2023) · Clinical Therapeutics · doi:10.1016/j.clinthera.2023.09.021 · Cited by 28
Mulholland, M., Depuydt, M. A. C., Jakobsson, G., Ljungcrantz, I., Grentzmann, A., To, F., Bengtsson, E., Gyllenbäck, E. J., Grönberg, C., Rattik, S., et al. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvae046 · Cited by 26
Xu, M., Xu, J.-J., Kang, L., Liu, Z., Su, M.-M., Zhao, W., Wang, Z.-H., Sun, L., Xiao, J., Evans, P. C., et al. (2024) · Acta Pharmacologica Sinica · doi:10.1038/s41401-024-01317-5 · Cited by 25
“In patients with chronic coronary artery disease, low-dose (0.5 mg/d orally) colchicine treatment can reduce major adverse cardiovascular events by 31% [58].”
InfluentialTsiachristas, A., Chan, K., Wahome, E., Kearns, B., Patel, P., Lyasheva, M., Syed, N., Fry, S., Halborg, T., West, H. W., et al. (2024) · European Heart Journal - Quality of Care and Clinical Outcomes · doi:10.1093/ehjqcco/qcae085 · Cited by 25
Pedretti, R. F. E., Asteggiano, R., Gevaert, A. B., Bowen, T. S., Caselli, S., Cornelissen, V., Christodorescu, R., Derosa, G., Diévart, F., Kurpas, D., et al. (2025) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwaf175 · Cited by 32
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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