Efficacy and safety of colchicine in patients with coronary artery disease: A systematic review and meta-analysis of randomized controlled trials


Ibadete Bytyçi| Gani Bajraktari | Peter E. Penson |Michael Y. Henein | Maciej Banach | the Lipid and Blood Pressure Meta-Analysis Collaboration (LBPMC) Group | the International Lipid Expert Panel (ILEP)

First published: 18 August 2021 | https://doi.org/10.1111/bcp.15041



Inflammation plays a central role in the pathogenesis and clinical manifestations of atherosclerosis. Randomized controlled trials have investigated the potential benefit of colchicine in reducing cardiovascular (CV) events in patients with coronary artery disease (CAD) but produced conflicting results. The aim of this meta-analysis was to evaluate the efficacy and safety of colchicine in patients with CAD.


We systematically searched selected electronic databases from inception until 10 December 2020. Primary clinical endpoints were: major adverse cardiac events; all-cause mortality; CV mortality; recurrent myocardial infarction; stroke; hospitalization; and adverse medication effects. Secondary endpoints were short-term effect of colchicine on inflammatory markers.


Twelve randomized controlled trials with a total of 13 073 patients with CAD (colchicine n = 6351 and placebo n = 6722) were included in the meta-analysis. At mean follow-up of 22.5 months, the colchicine group had lower risk of major adverse cardiac events (6.20 vs. 8.87%; P < .001), recurrent myocardial infarction (3.41 vs. 4.41%; P = .005), stroke (0.40 vs. 0.90%; P = .002) and hospitalization due to CV events (0.90 vs. 2.87%; P = .02) compared to the control group. The 2 patient groups had similar risk for all-cause mortality (2.08 vs. 1.88%; P = .82) and CV mortality (0.71 vs. 1.01%; P = .38). Colchicine significantly reduced high-sensitivity C-reactive protein (−4.25, P = .001) compared to controls but did not significantly affect interleukin (IL)-β1 and IL-18 levels.


Colchicine reduced CV events and inflammatory markers, high-sensitivity C-reactive protein and IL-6, in patients with coronary disease compared to controls. Its impact on cardiovascular and all-cause mortality requires further investigation.

Full content publication available for download


This meta-analysis was prepared independently; no company or institution supported it financially. No professional writer was involved in the preparation of this position paper.


Maciej Banach: speakers bureau: Amgen, Daichii Sankyo, Esperion, Herbapol, KRKA, MSD, Mylan, Novartis, Novo-Nordisk, Sanofi-Aventis, Servier; consultant to Abbott Vascular, Akcea, Amgen, Daichii Sankyo, Esperion, Lilly, MSD, Resverlogix, Sanofi-Aventis; Grants from Amgen, Mylan, Sanofi and Valeant. Gani Bajraktari: speakers bureau: KRKA, Bosnalijek, Novartis, LEK-Sandoz, Boston-Scientific, Trepharm and Alkaloid; consultant to Novartis. Peter E. Penson owns 4 shares in AstraZeneca PLC and has received honoraria and/or travel reimbursement for events sponsored by AKCEA, Amgen, AMRYT, Link Medical, Napp, Sanofi. Michael Y. Henein and Ibadete Bytyçi have no conflict of interest.


M.B.: Conceptualization, study design.; I.B.; G.B., M.B.; methodology, data sorting and statistical analysis; I.B., G.B., P.E., M.Y.H., M.B.; drafting the article or revising it critically for important intellectual content. All authors have read and agreed to the published version of the manuscript.

  1. Benjamin EJMuntner PAlonso A, et al. Heart disease and stroke Statistics-2019 update: a report from the American heart associationCirculation2019139e56e28.
  2. Libby PLoscalzo JRidker PM, et al. Inflammation, immunity, and infection in atherothrombosis: JACC review topic of the weekJ Am Coll Cardiol201872(17): 20712081.
  3. Ruscica MCorsini AFerri NBanach MSirtori CRClinical approach to the inflammatory etiology of cardiovascular diseasesPharmacol Res2020159104916.
  4. Ridker PMEverett BMThuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic diseaseN Engl J Med2017377(12): 11191131.
  5. Ridker PMEverett BMPradhan A, et al. Low-dose methotrexate for the prevention of atherosclerotic eventsN Engl J Med2019380(8): 752762.
  6. Eeiner ŽSirtori CRBanach MRuscica MSahebkar AMethotrexate for Cardiovascular Risk Reduction: The Right Choice? Angiology202071(2): 105107.
  7. Leung YYHui LLYKraus VBColchicine — update on mechanisms of action and therapeutic usesSemin Arthritis Rheum201545(3): 341350.
  8. Dalbeth NLauterio TJWolfe HRMechanism of action of colchicine in the treatment of goutClin Ther201436(10): 14651479.
  9. Cronstein BNMolad YReibman JBalakhane ELevin RIWeissmann GColchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophilsJ Clin Invest199596(2): 9941002.
  10. Bhattacharyya BPanda DGupta SBanerjee MAnti-Mitotic activity of colchicine and the structural basis for its interaction with tubulinMed Res Rev200828(1): 155183.
  11. Bonaventura AMontecucco FInflammation and pericarditis: are neutrophils actors behind the scenes? J Cell Physiol2019234(5): 53905398.
  12. Imazio MBrucato ACemin R, et al. A randomized trial of colchicine for acute pericarditisN Engl J Med2013 Oct 17; 369(16): 15221528.
  13. Imazio MBelli RBrucato A, et al. Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trialLancet2014 Jun 28; 383(9936): 22322237.
  14. Nidorf SMEikelboom JWBudgeon CAThompson PLLow-dose colchicines for secondary prevention of cardiovascular diseaseJ Am Coll Cardiol201361(4): 404410.
  15. Akodad MLattuca BNagot N, et al. COLIN trial: value of colchicine in the treatment of patients with acute myocardial infarction and inflammatory responseArch Cardiovasc Dis2017110(6-7): 395402.
  16. Deftereos SGiannopoulos GRaisakis K, et al. Colchicine treatment for the prevention of baremetal stent restenosis in diabetic patientsJ Am Coll Cardiol201361(16): 16791685.
  17. Hennessy TSoh LBowman M, et al. The Low Dose Colchicine after Myocardial Infarction (LoDoCo-MI) study: a pilot randomized placebo controlled trial of colchicine following acute myocardial infarctionAm Heart J20192156269.
  18. Tardif JCKouz SWaters DD, et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial InfarctionN Engl J Med2019 Dec 26; 381(26): 24972505.
  19. Shah BPillinger MZhong H, et al. Effects of acute colchicine administration prior to percutaneous coronary intervention: COLCHICINE-PCI randomized trialCirc Cardiovasc Interv202013:e008717.
  20. Bouabdallaoui NTardif JCWaters DD, et al. Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT)Euro Heart J2020 Aug 29;ehaa659.
  21. Nidorf SMFiolet ATLMosterd A, et al. Colchicine in Patients with Chronic Coronary DiseaseN Engl J Med2020383(19): 18381847https://doi.org/10.1056/NEJMoa2021372
  22. Page MJMcKenzie JEBossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviewsBMJ2021 Mar 29; 372n71.
  23. Green SCochrane handbook for systematic reviews of interventions version 5.1. 0 [updated March 2011]. The Cochrane Collaboration 2011.
  24. Cooper HMHedges LVThe Handbook of Research SynthesisNew York: Russell Sage Foundation; 1994.
  25. Hozo SPDjulbegovic BHozo IEstimating the mean and variance from the median, range, and the size of a sampleBMC Med Res Methodol20055(1): 13.
  26. Higgins JPThompson SGDeeks JJAltman DGMeasuring inconsistency in meta analysesBMJ2003327(7414): 557560.
  27. Abramson JAbramsonm ZMaking Sense of Data: A Self-Instruction Manual on the Interpretation of Epidemiological Data. Oxford University Press; 2001 ISBN 0-19-514525-9.
  28. Raju NCYi QNidorf MFagel NDHiralal REikelboom JWEffect of colchicine compared with placebo on high sensitivity C-reactive protein in patients with acute coronary syndrome or acute stroke: a pilot randomized controlled trialJ Thromb Thrombolysis201233(1): 8894.
  29. Nidorf SMEikelboom JWBudgeon CAThompson PLLow-dose colchicine for secondary prevention of cardiovascular diseaseJ Am Coll Cardiol201361(4): 404410.
  30. Deftereos SGiannopoulos GRaisakis K, et al. Colchicine treatment for the prevention of bare- metal stent restenosis in diabetic patientsJ Am Coll Cardiol201361(16): 16791685.
  31. Martínez GJRobertson SBarraclough J, et al. Colchicine Acutely Suppresses Local Cardiac Production of Inflammatory Cytokines in Patients With an Acute Coronary SyndromeJ Am Heart Assoc2015 Aug 24; 4(8):e002128.
  32. Robertson SMartínez GJPayet CA, et al. Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activationClin Sci (Lond)2016130(14): 12371246.
  33. Kajikawa MHigashi YTomiyama H, et al. Effect of short-term colchicine treatment on endothelial function in patients with coronary artery diseaseInt J Cardiol2019 Apr 15; 2813539.
  34. Tong DCQuinn SNasis A, et al. Colchicine in Patients with Acute Coronary Syndrome: The Australian COPS Randomized Clinical TrialCirculation2020142(20): 18901900https://doi.org/10.1161/CIRCULATIONAHA.120.050771
  35. GBDCauses of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017Lancet. 2017. 2018392(10159): 17361788.
  36. Roubille FTardif JCInflammation and the heart – prime time for new therapeutic approachesExpert Opin Emerg Drugs201318(3): 259261.
  37. Fox KACarruthers KFDunbar DR, et al. Underestimated and under- recognized: the late consequences of acute coronary syndrome (GRACE UK- Belgian Study)Eur Heart J201031(22): 27552764.
  38. Kato KYonetsu TKim SJ, et al. Nonculprit plaques in patients with acute coronary syndromes have more vulnerable features compared with those with non-acute coronary syndromes: a 3-vessel optical coherence tomography studyCirc Cardiovasc Imaging20125(4): 433440.
  39. Leung YYYao Hui LLKraus VBColchicine–update on mechanisms of action and therapeutic usesSemin Arthritis Rheum201545(3): 341350.
  40. Roubille FKritikou EBusseuil DBarrere-Lemaire STardif JCColchicine: an old wine in a new bottle? Antiinflamm Antiallergy Agents Med Chem201312(1): 1423.
  41. Vaidya KArnott CMartínez GJ, et al. Colchicine Therapy and Plaque Stabilization in Patients With Acute Coronary Syndrome: A CT Coronary Angiography StudyJACC Cardiovasc Imaging201811(2 Pt 2): 305316.
  42. Al-Abdouh ABarbarawi MKhan SU, et al. Colchicine therapy in patients with coronary artery disease: a systematic review and meta-analysis of randomized controlled trialsCoron Artery Dis202032(5): 441447https://doi.org/10.1097/MCA.0000000000000931
  43. Banach MPenson PEColchicine and Cardiovascular Outcomes: a Critical Appraisal of Recent StudiesCurr Atheroscler Rep2021 May 10; 23(7): 32https://doi.org/10.1007/s11883-021-00932-5