Systematic Review

University Cardiology, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy

‡Authors contributed equally

Alessandro Andreis‡

University Cardiology, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy

‡Authors contributed equally

Search for more papers by this author

Stefano Avondo

University Cardiology, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy

Search for more papers by this author

Matteo Pio Vaira

University Cardiology, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy

Search for more papers by this author

Massimo Imazio

*Author for correspondence:

E-mail Address: massimo.imazio@uniud.it; massimo_imazio@yahoo.it

https://orcid.org/0000-0002-5722-0245

Cardiology, Cardiothoracic Department, University Hospital “Santa Maria della Misericordia”, ASUFC, Udine, Italy

Search for more papers by this author

Published Online:5 Jul 2022https://doi.org/10.2217/fca-2020-0206

View article

Abstract

Aim: Colchicine, a microtubule-disassembling (antitubulin) agent used for centuries for the treatment of gout and autoimmune diseases, is a drug of growing interest in the cardiovascular field. While in the last decades it has become cornerstone of pericarditis treatment, it has also emerged in the last few years as a promising drug in the management of coronary artery disease, atrial fibrillation and heart failure. This systematic review and meta-analysis aimed to assess the efficacy of colchicine in patients with cardiovascular diseases. Methods: Systematic search in electronic databases (MEDLINE/PubMed, Scopus, BioMed Central, the Cochrane Collaboration Database of Randomized Trials, ClinicalTrials.gov, EMBASE, Google Scholar) was performed to identify randomized controlled trials (RCTs) up to February 2021. Random-effects meta-analysis was performed to assess the risk of cardiovascular events, defined according to clinical setting. Results: Among 15,569 pooled patients from 21 RCTs, colchicine was superior to placebo in the reduction of cardiovascular events. In the setting of pericardial diseases, it was associated with a lower risk of recurrent pericarditis (17 vs 34%, RR = 0.50, 95% CI: 0.42–0.60, I² = 10%). In other studies assessing coronary artery disease patients, colchicine was associated with a reduced risk of major adverse cardiovascular events (MACE) such as myocardial infarction, stroke, cardiovascular death, coronary revascularisation and hospitalization (6.3 vs 9%, RR = 0.67, 95% CI: 0.54–0.84, I² = 55). Among patients with atrial fibrillation, it was associated with lower rates of recurrence (20 vs 30%, RR = 0.68, 95% CI: 0.58–0.81, I² = 0). In the single RCT on heart failure, colchicine was not associated with improved NYHA class. Conclusion: Colchicine is a valuable anti-inflammatory agent for the prevention of cardiovascular events in patients with inflammatory cardiac conditions such as pericardial diseases, coronary artery disease and atrial fibrillation.

Plain language summary

Colchicine is an ancient drug with anti-inflammatory properties, classically used for gout and autoimmune diseases. While in the last decades it has become cornerstone for the treatment of pericarditis, in the last few years is emerging as a promising drug in the setting of coronary artery disease, heart failure and arrhythmias. Due to promising findings, almost ten trials are currently ongoing to investigate novel applications, which will be discussed throughout the paper. The aim of this systematic review and meta-analysis is to provide an overview of the latest evidence on colchicine, a microtubule-disassembling (antitubulin) agent, for the treatment and prevention of cardiovascular diseases and to discuss possible future applications.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. Golia E, Limongelli G, Natale F et al. Inflammation and cardiovascular disease: from pathogenesis to therapeutic target. Curr. Atheroscler. Rep. 16(9), 435 (2014).
MedlineGoogle Scholar
2. Liberale L, Montecucco F, Schwarz L, Lüscher TF, Camici GG. Inflammation and cardiovascular diseases: lessons from seminal clinical trials. Cardiovasc. Res. 117(2), 411–422 (2021). • Recent review highlighting the newest evidences of inflammation and cardiovascular diseases.
Medline CASGoogle Scholar
3. Dasgeb B, Kornreich D, McGuinn K, Okon L, Brownell I, Sackett DL. Colchicine: an ancient drug with novel applications. Br. J. Dermatol. 178(2), 350–356 (2018).
Medline CASGoogle Scholar
4. Deftereos S, Giannopoulos G, Papoutsidakis N et al. Colchicine and the heart: pushing the envelope. J. Am. Coll. Cardiol. 62(20), 1817–1825 (2013).
Medline CASGoogle Scholar
5. Bonaventura A, Montecucco F. Inflammation and pericarditis: are neutrophils actors behind the scenes? J. Cell. Physiol. 234(5), 5390–5398 (2019).
Medline CASGoogle Scholar
6. 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. 28(1), 155–183 (2008).
Medline CASGoogle Scholar
7. Chaldakov GN. Colchicine, a microtubule-disassembling drug, in the therapy of cardiovascular diseases. Cell Biol. Int. 42(8), 1079–1084 (2018).
MedlineGoogle Scholar
8. Chaldakov GN. Antitubulins–a new therapeutic approach for atherosclerosis? Atherosclerosis 44(3), 385–390 (1982).
Medline CASGoogle Scholar
9. Chaldakov GN, Vankov VN. Morphological aspects of secretion in the arterial smooth muscle cell, with special reference to the Golgi complex and microtubular cytoskeleton. Atherosclerosis 61(3), 175–192 (1986).
Medline CASGoogle Scholar
10. Yanev S, Zhelyazkova-Savova M, Chaldakov GN. The fibrous cap: a promising target in the pharmacotherapy of atherosclerosis. Biomed. Rev. 30(0), 136–141 (2019).
CASGoogle Scholar
11. Cronstein BN, Molad Y, Reibman J, Balakhane E, Levin RI, Weissmann G. Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils. J. Clin. Invest. 96(2), 994–1002 (1995).
Medline CASGoogle Scholar
12. Groslambert M, Py BF. Spotlight on the NLRP3 inflammasome pathway. J. Inflamm. Res. 11, 359–374 (2018).
Medline CASGoogle Scholar
13. Slobodnick A, Shah B, Krasnokutsky S, Pillinger MH. Update on colchicine, 2017. Rheumatol. Oxf. Engl. 57(Suppl. 1), i4–i11 (2018).
Medline CASGoogle Scholar
14. Ferron GM, Rochdi M, Jusko WJ, Scherrmann J-M. Oral absorption characteristics and pharmacokinetics of colchicine in healthy volunteers after single and multiple doses. J. Clin. Pharmacol. 36(10), 874–883 (1996).
Medline CASGoogle Scholar
15. Chappey ON, Niel E, Wautier JL et al. Colchicine disposition in human leukocytes after single and multiple oral administration. Clin. Pharmacol. Ther. 54(4), 360–367 (1993).
Medline CASGoogle Scholar
16. Stewart S, Yang KCK, Atkins K, Dalbeth N, Robinson PC. Adverse events during oral colchicine use: a systematic review and meta-analysis of randomised controlled trials. Arthritis Res. Ther. 22(1), 28 (2020).
Medline CASGoogle Scholar
17. Imazio M, Brucato A, Lazaros G et al. Anti-inflammatory therapies for pericardial diseases in the COVID-19 pandemic: safety and potentiality. J. Cardiovasc. Med. Hagerstown Md. 21(9), 625–629 (2020). •• Describes the safety of anti-inflammatory therapies (including colchicine) during the COVID 19 pandemic.
Medline CASGoogle Scholar
18. Andreis A, Imazio M, Avondo S et al. Adverse events of colchicine for cardiovascular diseases: a comprehensive meta-analysis of 14 188 patients from 21 randomized controlled trials. J. Cardiovasc. Med. Hagerstown Md. 21 (2021).
Google Scholar
19. Brucato A, Pluymaekers N, Tombetti E et al. Management of idiopathic recurrent pericarditis during pregnancy. Int. J. Cardiol. 282, 60–65 (2019).
MedlineGoogle Scholar
20. Imazio M, Bobbio M, Cecchi E et al. Colchicine in addition to conventional therapy for acute pericarditis: results of the COlchicine for acute PEricarditis (COPE) trial. Circulation 112(13), 2012–2016 (2005).
Medline CASGoogle Scholar
21. Imazio M, Brucato A, Cemin R et al. Colchicine for recurrent pericarditis (CORP): a randomized trial. Ann. Intern. Med. 155(7), 409–414 (2011).
MedlineGoogle Scholar
22. Imazio M, Bobbio M, Cecchi E et al. Colchicine as first-choice therapy for recurrent pericarditis: results of the CORE (COlchicine for REcurrent pericarditis) trial. Arch. Intern. Med. 165(17), 1987–1991 (2005).
Medline CASGoogle Scholar
23. Imazio M, Trinchero R, Brucato A et al. COlchicine for the Prevention of the Post-pericardiotomy Syndrome (COPPS): a multicentre, randomized, double-blind, placebo-controlled trial. Eur. Heart J. 31(22), 2749–2754 (2010).
Medline CASGoogle Scholar
24. Imazio M, Brucato A, Cemin R et al. A randomized trial of colchicine for acute pericarditis. N. Engl. J. Med. 369(16), 1522–1528 (2013).
Medline CASGoogle Scholar
25. Imazio M, Belli R, Brucato A 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 Lond. Engl. 383(9936), 2232–2237 (2014).
Medline CASGoogle Scholar
26. Imazio M, Brucato A, Ferrazzi P et al. Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation: the COPPS-2 randomized clinical trial. JAMA 312(10), 1016–1023 (2014).
Medline CASGoogle Scholar
27. Sambola A, Roca Luque I, Mercé J et al. Colchicine administered in the first episode of acute idiopathic pericarditis: a randomized multicenter open-label study. Rev. Espanola Cardiol. Engl. Ed 72(9), 709–716 (2019).
MedlineGoogle Scholar
28. Shah B, Pillinger M, Zhong H et al. Effects of acute colchicine administration prior to percutaneous coronary intervention: COLCHICINE-PCI randomized trial. Circ. Cardiovasc. Interv. 13(4), e008717 (2020).
Medline CASGoogle Scholar
29. Nidorf SM, Eikelboom JW, Budgeon CA, Thompson PL. Low-dose colchicine for secondary prevention of cardiovascular disease. J. Am. Coll. Cardiol. 61(4), 404–410 (2013).
Medline CASGoogle Scholar
30. Nidorf SM, Fiolet ATL, Mosterd A et al. Colchicine in patients with chronic coronary disease. N. Engl. J. Med. 383(19), 1838–1847 (2020). •• Randomized trial of patient with stable coronary artery disease, randomized to colchicine or placebo.
Medline CASGoogle Scholar
31. Tardif J-C, Kouz S, Waters DD et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N. Engl. J. Med. 381(26), 2497–2505 (2019). •• Randomized trial that proved efficacy of colchicine in reducing cardiovascular events in patients with a recent myocardial infarction.
Medline CASGoogle Scholar
32. Tong DC, Quinn S, Nasis A et al. Colchicine in patients with acute coronary syndrome: The Australian COPS Randomized Clinical Trial. Circulation 142(20), 1890–1900 (2020).
MedlineGoogle Scholar
33. Deftereos S, Giannopoulos G, Kossyvakis C et al. Colchicine for prevention of early atrial fibrillation recurrence after pulmonary vein isolation: a randomized controlled study. J. Am. Coll. Cardiol. 60(18), 1790–1796 (2012).
Medline CASGoogle Scholar
34. Imazio M, Brucato A, Ferrazzi P et al. teduces postoperative atrial fibrillation: results of the Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) atrial fibrillation substudy. Circulation 124(21), 2290–2295 (2011).
Medline CASGoogle Scholar
35. Tabbalat RA, Hamad NM, Alhaddad IA, Hammoudeh A, Akasheh BF, Khader Y. Effect of ColchiciNe on the InciDence of atrial fibrillation in open heart surgery patients: END-AF trial. Am. Heart J. 178, 102–107 (2016).
MedlineGoogle Scholar
36. Zarpelon CS, Netto MC, Jorge JCM et al. Colchicine to reduce atrial fibrillation in the postoperative period of myocardial revascularization. Arq. Bras. Cardiol. 107(1), 4–9 (2016).
MedlineGoogle Scholar
37. Deftereos S, Giannopoulos G, Efremidis M et al. Colchicine for prevention of atrial fibrillation recurrence after pulmonary vein isolation: mid-term efficacy and effect on quality of life. Heart Rhythm 11(4), 620–628 (2014).
MedlineGoogle Scholar
38. Deftereos S, Giannopoulos G, Panagopoulou V et al. Anti-inflammatory treatment with colchicine in stable chronic heart failure: a prospective, randomized study. JACC Heart Fail. 2(2), 131–137 (2014).
MedlineGoogle Scholar
39. Adler Y, Charron P, Imazio M et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC) Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS). Eur. Heart J. 36(42), 2921–2964 (2015).
MedlineGoogle Scholar
40. Andreis A, Imazio M, de Ferrari GM. Contemporary diagnosis and treatment of recurrent pericarditis. Expert Rev. Cardiovasc. Ther. 17(11), 817–826 (2019).
Medline CASGoogle Scholar
41. Millaire A, Ducloux G. Treatment of acute or recurrent pericarditis with colchicine. Circulation 83(4), 1458–1459 (1991).
Medline CASGoogle Scholar
42. Finkelstein Y, Shemesh J, Mahlab K et al. Colchicine for the prevention of postpericardiotomy syndrome. Herz 27(8), 791–794 (2002).
MedlineGoogle Scholar
43. Cecconi A, Vilchez-Tschischke JP, Mateo J et al. Effects of colchicine on atherosclerotic plaque stabilization: a multimodality imaging study in an animal model. J. Cardiovasc. Transl. Res. 14(1), 1–11 (2021). • Provides interesting insights on anti atherosclerotic effects of colchicine in animal model.
MedlineGoogle Scholar
44. Imazio M, Andreis A, Brucato A, Adler Y, De Ferrari GM. Colchicine for acute and chronic coronary syndromes. Heart Br. Card. Soc. 106(20), 1555–1560 (2020).
CASGoogle Scholar
45. Rajamäki K, Lappalainen J, Oörni K et al. Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation. PloS One 5(7), e11765 (2010).
MedlineGoogle Scholar
46. Duewell P, Kono H, Rayner KJ et al. NLRP3 inflamasomes are required for atherogenesis and activated by cholesterol crystals that form early in disease. Nature 464(7293), 1357–1361 (2010).
Medline CASGoogle Scholar
47. Wójcicki J, Hinek A, Jaworska M, Samochowiec L. The effect of colchicine on the development of experimental atherosclerosis in rabbits. Pol. J. Pharmacol. Pharm. 38(4), 343–348 (1986).
Medline CASGoogle Scholar
48. Hollander W, Paddock J, Nagraj S, Colombo M, Kirkpatrick B. Effects of anticalcifying and antifibrobrotic drugs on pre-established atherosclerosis in the rabbit. Atherosclerosis 33(1), 111–123 (1979).
Medline CASGoogle Scholar
49. Freed M, Safian RD, O'Neill WW, Safian M, Jones D, Grines CL. Combination of lovastatin, enalapril, and colchicine does not prevent restenosis after percutaneous transluminal coronary angioplasty. Am. J. Cardiol. 76(16), 1185–1188 (1995).
Medline CASGoogle Scholar
50. O'Keefe JH, McCallister BD, Bateman TM, Kuhnlein DL, Ligon RW, Hartzler GO. Ineffectiveness of colchicine for the prevention of restenosis after coronary angioplasty. J. Am. Coll. Cardiol. 19(7), 1597–1600 (1992).
MedlineGoogle Scholar
51. Vaidya K, Arnott C, Martínez GJ et al. Colchicine therapy and plaque stabilization in patients with acute coronary syndrome: a CT coronary angiography study. JACC Cardiovasc. Imaging 11(2 Pt 2), 305–316 (2018).
MedlineGoogle Scholar
52. Deftereos S, Giannopoulos G, Angelidis C et al. Anti-inflammatory treatment with colchicine in acute myocardial infarction: a pilot study. Circulation 132(15), 1395–1403 (2015).
Medline CASGoogle Scholar
53. Solomon DH, Liu C-C, Kuo I-H, Zak A, Kim SC. Effects of colchicine on risk of cardiovascular events and mortality among patients with gout: a cohort study using electronic medical records linked with Medicare claims. Ann. Rheum. Dis. 75(9), 1674–1679 (2016).
Medline CASGoogle Scholar
54. Fujisue K, Sugamura K, Kurokawa H et al. Colchicine improves survival, left ventricular remodeling, and chronic cardiac function after acute myocardial infarction. Circ. J. Off. J. Jpn. Circ. Soc. 81(8), 1174–1182 (2017).
Medline CASGoogle Scholar
55. Cooper G. Cytoskeletal networks and the regulation of cardiac contractility: microtubules, hypertrophy, and cardiac dysfunction. Am. J. Physiol. Heart Circ. Physiol. 291(3), H1003–H1014 (2006).
Medline CASGoogle Scholar
56. Klein AL, Imazio M, Cremer P et al. Phase 3 trial of interleukin-1 trap rilonacept in recurrent pericarditis. N. Engl. J. Med. 384(1), 31–41 (2021).
Medline CASGoogle Scholar
57. Brucato A, Imazio M, Gattorno M et al. Effect of anakinra on recurrent pericarditis among patients with colchicine resistance and corticosteroid dependence: the AIRTRIP randomized clinical trial. JAMA 316(18), 1906–1912 (2016).
MedlineGoogle Scholar
58. Imazio M, Andreis A, De Ferrari GM et al. Anakinra for corticosteroid-dependent and colchicine-resistant pericarditis: the IRAP (International Registry of Anakinra for Pericarditis) study. Eur. J. Prev. Cardiol. 27(9)956–964 (2019).
MedlineGoogle Scholar
59. Andreis A, Imazio M, Giustetto C, Brucato A, Adler Y, Ferrari GMD. Anakinra for constrictive pericarditis associated with incessant or recurrent pericarditis. Heart 106(20), 1540–1542 (2020).
MedlineGoogle Scholar
60. Imazio M, Andreis A, Piroli F et al. Anti-interleukin 1 agents for the treatment of recurrent pericarditis: a systematic review and meta-analysis. Heart Br. Card. Soc. doi: heartjnl-2020-318869 (2021) (Epub ahead of print).
Google Scholar
61. Imazio M. Anti-IL-1 agents: a paradigm shift in medical therapy for recurrent pericarditis? Heart doi:heartjnl-2020-318549 (2020) (Epub ahead of print). •• Comment on the new anti-IL-1 drugs for pericarditis, and the possible association with colchicine.
Google Scholar
62. Martínez GJ, Robertson S, Barraclough J et al. Colchicine acutely suppresses local cardiac production of inflammatory cytokines in patients with an acute coronary syndrome. J. Am. Heart Assoc. 4(8), e002128 (2015).
MedlineGoogle Scholar
63. Robertson S, Martínez GJ, Payet CA et al. Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation. Clin. Sci. Lond. Engl. 1979 130(14), 1237–1246 (2016).
CASGoogle Scholar
64. Andreis A, Imazio M, De Ferrari GM. Colchicine for the treatment of cardiovascular diseases: old drug, new targets. J. Cardiovasc. Med. Hagerstown Md. 22(1), 1–8 (2021).
Medline CASGoogle Scholar
65. Ho KM, Tan JA. Benefits and risks of corticosteroid prophylaxis in adult cardiac surgery: a dose-response meta-analysis. Circulation 119(14), 1853–1866 (2009).
Medline CASGoogle Scholar
66. Hemkens LG, Ewald H, Gloy VL et al. Cardiovascular effects and safety of long-term colchicine treatment: cochrane review and meta-analysis. Heart Br. Card. Soc. 102(8), 590–596 (2016).
CASGoogle Scholar
67. Imazio M, Andreis A, De Ferrari GM. COVID-19 and myocardial injury: is there a role for interleukin-1 inhibition? J. Cardiovasc. Med. Hagerstown Md. 21(7), 465–466 (2020).
Medline CASGoogle Scholar
68. Deftereos SG, Giannopoulos G, Vrachatis DA et al. Effect of colchicine vs standard care on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019: the GRECCO-19 randomized clinical trial. JAMA Netw. Open 3(6), e2013136 (2020).
MedlineGoogle Scholar

Vol. 18, No. 8

Supplemental Materials

Metrics

Downloaded 456 times

History

Received 25 November 2020

Accepted 4 June 2021

Published online 5 July 2022

Published in print August 2022

Information

Keywords

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fca-2020-0206

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

PDF download

Colchicine for cardiovascular medicine: a systematic review and meta-analysis

Abstract

Plain language summary

References