Skip to main content
Log in

Colchicine in the Management of Acute and Chronic Coronary Artery Disease

  • Pericardial Disease (L Klein and CL Jellis, Section Editors
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Inflammation is involved in the initiation, progression, and destabilization of atherosclerosis. Anti-inflammatory strategies aimed at reducing residual cardiovascular (CV) risk have gained increasing interest in addition to the traditional management of risk factors. Colchicine is a potent anti-inflammatory therapy that affects the inflammasome and other targets. We will herein review the most recent evidence regarding the usefulness of colchicine in patients with coronary artery disease (CAD).

Recent Findings

Colchicine has recently been repurposed from its traditional use to a number of CV indications. The landmark COLCOT and LoDoCo2 trials have demonstrated that long-term use of colchicine was associated with a reduced rate of CV events in both acute and chronic presentations of CAD, with an overall good safety profile.

Summary

Colchicine is emerging as a valuable, safe, and cost-effective therapy in addition to standard of care for the prevention of atherothrombotic events in CAD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1

Similar content being viewed by others

Abbreviations

CANTOS:

Canakinumab Anti-inflammatory Thrombosis Outcome Study

CIRT:

Cardiovascular Inflammation Reduction Trial

COLCOT:

Colchicine Cardiovascular Outcomes Trial

COPS:

Colchicine in Patients with Acute Coronary Syndrome trial

CORP:

Colchicine for Recurrent Pericarditis

CORP-2:

Efficacy and Safety of Colchicine for Treatment of Multiple Recurrences of Pericarditis

ICAP:

Investigation on Colchicine for Acute Pericarditis

LoDoCo:

Low-Dose Colchicine trial

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al. Heart Disease and Stroke Statistics-2019 update: a report from the American Heart Association. Circulation. 2019;139(10):e56–e528.

    Article  PubMed  Google Scholar 

  2. Roth GA, Huffman MD, Moran AE, Feigin V, Mensah GA, Naghavi M, et al. Global and regional patterns in cardiovascular mortality from 1990 to 2013. Circulation. 2015;132(17):1667–78.

    Article  PubMed  Google Scholar 

  3. Jernberg T, Hasvold P, Henriksson M, Hjelm H, Thuresson M, Janzon M. Cardiovascular risk in post-myocardial infarction patients: nationwide real world data demonstrate the importance of a long-term perspective. Eur Heart J. 2015;36(19):1163–70.

    Article  PubMed  Google Scholar 

  4. Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. J Am Coll Cardiol. 2016;68(10):1082–115.

    Article  PubMed  Google Scholar 

  5. Ridker PM. Residual inflammatory risk: addressing the obverse side of the atherosclerosis prevention coin. Eur Heart J. 2016;37(22):1720–2.

    Article  PubMed  Google Scholar 

  6. Rymer JA, Newby LK. Failure to launch: targeting inflammation in acute coronary syndromes. JACC Basic Transl Sci. 2017;2(4):484–97.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Libby P, Ridker PM, Hansson GK. Leducq Transatlantic Network on A. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol. 2009;54(23):2129–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ridker PM. From CANTOS to CIRT to COLCOT to clinic: will all atherosclerosis patients soon be treated with combination lipid-lowering and inflammation-inhibiting agents? Circulation. 2020;141(10):787–9.

    Article  PubMed  Google Scholar 

  9. Hartung EF. History of the use of colchicum and related medicaments in gout; with suggestions for further research. Ann Rheum Dis. 1954;13(3):190–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ravelli RB, Gigant B, Curmi PA, Jourdain I, Lachkar S, Sobel A, et al. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature. 2004;428(6979):198–202.

    Article  CAS  PubMed  Google Scholar 

  11. Leung YY, Yao Hui LL, Kraus VB. Colchicine--Update on mechanisms of action and therapeutic uses. Semin Arthritis Rheum. 2015;45(3):341–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Mulay SR, Anders HJ. Crystallopathies. N Engl J Med. 2016;374(25):2465–76.

    Article  CAS  PubMed  Google Scholar 

  13. Imazio M, Brucato A, Cemin R, Ferrua S, Maggiolini S, Beqaraj F, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013;369(16):1522–8.

    Article  CAS  PubMed  Google Scholar 

  14. Sari I, Yuksel A, Kozaci D, Selcuk S, Gokce G, Yildiz Y, et al. The effect of regular colchicine treatment on biomarkers related with vascular injury in newly diagnosed patients with familial Mediterranean fever. Inflammation. 2012;35(3):1191–7.

    Article  CAS  PubMed  Google Scholar 

  15. Bhattacharyya B, Panda D, Gupta S, Banerjee M. Anti-mitotic activity of colchicine and the structural basis for its interaction with tubulin. Med Res Rev. 2008;28(1):155–83.

    Article  CAS  PubMed  Google Scholar 

  16. Martinez GJ, Celermajer DS, Patel S. Corrigendum to: "The NLRP3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation". Atherosclerosis. 2018;269:262–71.

    Article  CAS  PubMed  Google Scholar 

  17. •• Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med. 2019;381(26):2497–505 This is a landmark study of colchicine in patients post-MI.

    Article  CAS  PubMed  Google Scholar 

  18. •• Nidorf SM, ATL F, Mosterd A, Eikelboom JW, Schut A, TSJ O, et al. Colchicine in patients with chronic coronary disease. N Engl J Med. 2020;383(19):1838–47 This is a landmark study of colchicine in patients with chronic CAD.

    Article  CAS  PubMed  Google Scholar 

  19. •• Libby P, Loscalzo J, Ridker PM, Farkouh ME, Hsue PY, Fuster V, et al. Inflammation, immunity, and infection in atherothrombosis: JACC review topic of the week. J Am Coll Cardiol. 2018;72(17):2071–81 This is one of the most thorough reviews detailing the role of inflammation in atherothrombosis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352(16):1685–95.

    Article  CAS  PubMed  Google Scholar 

  21. Naruko T, Ueda M, Haze K, van der Wal AC, van der Loos CM, Itoh A, et al. Neutrophil infiltration of culprit lesions in acute coronary syndromes. Circulation. 2002;106(23):2894–900.

    Article  PubMed  Google Scholar 

  22. Soehnlein O. Multiple roles for neutrophils in atherosclerosis. Circ Res. 2012;110(6):875–88.

    Article  CAS  PubMed  Google Scholar 

  23. Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med. 2005;352(1):20–8.

    Article  CAS  PubMed  Google Scholar 

  24. Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E. Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation. 1999;100(3):230–5.

    Article  CAS  PubMed  Google Scholar 

  25. Ridker PM. Clinician’s guide to reducing inflammation to reduce atherothrombotic risk: JACC review topic of the week. J Am Coll Cardiol. 2018;72(25):3320–31.

    Article  PubMed  Google Scholar 

  26. Varas-Lorenzo C, Rodriguez LA, Maguire A, Castellsague J, Perez-Gutthann S. Use of oral corticosteroids and the risk of acute myocardial infarction. Atherosclerosis. 2007;192(2):376–83.

    Article  CAS  PubMed  Google Scholar 

  27. Bolten WW. Problem of the atherothrombotic potential of non-steroidal anti-inflammatory drugs. Ann Rheum Dis. 2006;65(1):7–13.

    Article  CAS  PubMed  Google Scholar 

  28. •• Ridker PM, Everett BM, Thuren T, JG MF, Chang WH, Ballantyne C, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12):1119–31 This is the first paper that showed the clinical benefits of inflammation reduction in patients with coronary artery disease.

    Article  CAS  PubMed  Google Scholar 

  29. Ridker PM, Everett BM, Pradhan A, MacFadyen JG, Solomon DH, Zaharris E, et al. Low-dose methotrexate for the prevention of atherosclerotic events. N Engl J Med. 2019;380(8):752–62.

    Article  CAS  PubMed  Google Scholar 

  30. Abela GS, Aziz K, Vedre A, Pathak DR, Talbott JD, Dejong J. Effect of cholesterol crystals on plaques and intima in arteries of patients with acute coronary and cerebrovascular syndromes. Am J Cardiol. 2009;103(7):959–68.

    Article  CAS  PubMed  Google Scholar 

  31. Abela GS, Aziz K. Cholesterol crystals rupture biological membranes and human plaques during acute cardiovascular events--a novel insight into plaque rupture by scanning electron microscopy. Scanning. 2006;28(1):1–10.

    Article  CAS  PubMed  Google Scholar 

  32. Kellner-Weibel G, Yancey PG, Jerome WG, Walser T, Mason RP, Phillips MC, et al. Crystallization of free cholesterol in model macrophage foam cells. Arterioscler Thromb Vasc Biol. 1999;19(8):1891–8.

    Article  CAS  PubMed  Google Scholar 

  33. Rajamaki K, Lappalainen J, Oorni K, Valimaki E, Matikainen S, Kovanen PT, et al. Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation. PLoS One. 2010;5(7):e11765.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010;464(7293):1357–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Libby P, Tabas I, Fredman G, Fisher EA. Inflammation and its resolution as determinants of acute coronary syndromes. Circ Res. 2014;114(12):1867–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440(7081):237–41.

    Article  CAS  PubMed  Google Scholar 

  37. Samstad EO, Niyonzima N, Nymo S, Aune MH, Ryan L, Bakke SS, et al. Cholesterol crystals induce complement-dependent inflammasome activation and cytokine release. J Immunol. 2014;192(6):2837–45.

    Article  CAS  PubMed  Google Scholar 

  38. Chappey ON, Niel E, Wautier JL, Hung PP, Dervichian M, Cattan D, et al. Colchicine disposition in human leukocytes after single and multiple oral administration. Clin Pharmacol Ther. 1993;54(4):360–7.

    Article  CAS  PubMed  Google Scholar 

  39. Perico N, Ostermann D, Bontempeill M, Morigi M, Amuchastegui CS, Zoja C, et al. Colchicine interferes with L-selectin and leukocyte function-associated antigen-1 expression on human T lymphocytes and inhibits T cell activation. J Am Soc Nephrol. 1996;7(4):594–601.

    Article  CAS  PubMed  Google Scholar 

  40. Deftereos S, Giannopoulos G, Angelidis C, Alexopoulos N, Filippatos G, Papoutsidakis N, et al. Anti-inflammatory treatment with colchicine in acute myocardial infarction: a pilot study. Circulation. 2015;132(15):1395–403.

    Article  CAS  PubMed  Google Scholar 

  41. Nidorf SM, Eikelboom JW, Budgeon CA, Thompson PL. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol. 2013;61(4):404–10.

    Article  CAS  PubMed  Google Scholar 

  42. Tong DC, Quinn S, Nasis A, Hiew C, Roberts-Thomson P, Adams H, et al. Colchicine in Patients With Acute Coronary Syndrome: the Australian COPS Randomized Clinical Trial. Circulation. 2020;142(20):1890–900.

    Article  PubMed  Google Scholar 

  43. Bouabdallaoui N, Tardif JC, Waters DD, Pinto FJ, Maggioni AP, Diaz R, et al. Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT). Eur Heart J. 2020;41(42):4092–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Munk PS, Breland UM, Aukrust P, Skadberg O, Ueland T, Larsen AI. Inflammatory response to percutaneous coronary intervention in stable coronary artery disease. J Thromb Thrombolysis. 2011;31(1):92–8.

    Article  CAS  PubMed  Google Scholar 

  45. Martinez GJ, Robertson S, Barraclough J, Xia Q, Mallat Z, Bursill C, et al. Colchicine acutely suppresses local cardiac production of inflammatory cytokines in patients with an acute coronary syndrome. J Am Heart Assoc. 2015;4(8):e002128.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Shah B, Pillinger M, Zhong H, Cronstein B, Xia Y, Lorin JD, et al. Effects of acute colchicine administration prior to percutaneous coronary intervention: COLCHICINE-PCI Randomized Trial. Circ Cardiovasc Interv. 2020;13(4):e008717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. •• Samuel M, Tardif JC, Bouabdallaoui N, Khairy P, Dube MP, Blondeau L, et al. Colchicine for secondary prevention of cardiovascular disease: a systematic review and meta-analysis of randomized controlled trials. Can J Cardiol. 2020; This is an important paper detailing long-term benefits and safety of colchicine in patients with CAD.

  48. Samuel M, Tardif JC, Khairy P, Roubille F, Waters DD, Gregoire JC, et al. Cost-effectiveness of low-dose colchicine after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT). Eur Heart J Qual Care Clin Outcomes. 2020.

  49. Imazio M, Brucato A, Cemin R, Ferrua S, Maggiolini S, Beqaraj F, et al. ICAP Investigators. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013;369(16):1522–8.

    Article  CAS  PubMed  Google Scholar 

  50. Imazio M, Brucato A, Cemin R, Ferrua S, Belli R, Maestroni S, et al. CORP (COlchicine for Recurrent Pericarditis) Investigators. Colchicine for recurrent pericarditis (CORP): a randomized trial. Ann Intern Med. 2011;155(7):409–14.

    Article  PubMed  Google Scholar 

  51. Imazio M, Belli R, Brucato A, Cemin R, Ferrua S, Beqaraj F, et al. Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial. Lancet. 2014;383(9936):2232–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jean-Claude Tardif.

Ethics declarations

Conflict of Interest

Dr. Bouabdallaoui reports personal fees from AstraZeneca, outside the submitted work. Dr. Tardif reports grants from Amarin; grants and personal fees from AstraZeneca; grants from Ceapro; grants, personal fees, and minor equity interest from DalCor; grants from Esperion; personal fees from HLS Therapeutics; grants from Ionis; personal fees from Pendopharm; grants from REGENXBIO; and grants and personal fees from Sanofi, outside the submitted work. In addition, Dr. Tardif has a patent pending on use of colchicine after myocardial infarction (but he has waived all rights and does not stand to gain financially from the patent).

Human and Animal Rights and Informed Consent

This is a review article. Please refer to each cited study for details regarding ethics approval.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Pericardial Disease

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bouabdallaoui, N., Tardif, JC. Colchicine in the Management of Acute and Chronic Coronary Artery Disease. Curr Cardiol Rep 23, 120 (2021). https://doi.org/10.1007/s11886-021-01560-w

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11886-021-01560-w

Keywords

Navigation