Skip to main content
Log in

Inflammation May be the Future of Cardiovascular Risk Reduction: Does Colchicine have a Current Indication?

  • Review Article
  • Published:
American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Inflammation as a cardiovascular risk factor has attracted increasing attention . The current standard of care for decreasing the occurrence of cardiovascular events includes controlling risk factors such as hypertension and maximizing the lowering of low-density lipoprotein cholesterol (LDL-C). However, a recent study demonstrated decreased cardiovascular risk with the anti-inflammatory agent canakinumab and created more interest in decreasing cardiovascular risk by decreasing inflammation. Canakinumab is not yet approved and will undoubtedly be very expensive, so interest in an established medication such as colchicine, which is inexpensive to produce, is appropriate if evidence-based benefit is adequately confirmed. Colchicine has existing indications for gout and familial Mediterranean fever and for decreasing the incidence of postpericardiotomy syndrome. If an evidence-based benefit in decreasing cardiovascular risk can be demonstrated for colchicine, it will be of significant importance. Meta-analyses and observational studies have provided evidence to suggest that colchicine decreases cardiovascular risk because of its anti-inflammatory effects. However, randomized controlled trials (RCTs) are needed, and the recently published COLCOT (Colchicine Cardiovascular Outcomes Trial) showed definite benefit on cardiovascular outcomes in adults who had experienced a myocardial infarction within the previous 30 days. Sufficient evidence now supports the use of colchicine for secondary prevention in patients at the highest cardiovascular risk who continue to have cardiovascular events despite good blood pressure control and maximum LDL-C reduction. Nevertheless, more RCTs will be necessary before widespread general use of colchicine in cardiovascular disease prevention can be recommended. The current acquisition cost issues with colchicine also need to be resolved.

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.

Fig. 1

Similar content being viewed by others

References

  1. Shekelle PG, Newberry SJ, FitzGerald JD, Motala A, O’Hanlon CE, Tariq A, et al. Management of gout: a systematic review in support of an american college of physicians clinical practice guideline. Ann Intern Med. 2017;166(1):37–51.

    PubMed  Google Scholar 

  2. Thompson PL. Colchicine in cardiovascular disease: repurposing an ancient gout drug. Clin Ther. 2019;41(1):8–10.

    PubMed  Google Scholar 

  3. Ben-Chetrit E, Bergmann S, Sood R. Mechanism of the anti-inflammatory effect of colchicine in rheumatic diseases: a possible new outlook through microarray analysis. Rheumatology (Oxford). 2006;45(3):274–82.

    CAS  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Dalbeth N, Lauterio TJ, Wolfe HR. Mechanism of action of colchicine in the treatment of gout. Clin Ther. 2014;36(10):1465–79.

    CAS  PubMed  Google Scholar 

  6. Titanji B, Gavegnano C, Hsue P, Schinazi R, Marconi VC. Targeting inflammation to reduce atherosclerotic cardiovascular risk in people with HIV infection. J Am Heart Assoc. 2020;9(3):e014873.

    PubMed  PubMed Central  Google Scholar 

  7. Imazio M, Brucato A, Belli R, Forno D, Ferro S, Trinchero R, et al. Colchicine for the prevention of pericarditis: what we know and what we do not know in 2014—systematic review and meta-analysis. J Cardiovasc Med (Hagerstown). 2014;15(12):840–6.

    CAS  Google Scholar 

  8. Imazio M, Brucato A, Forno D, Ferro S, Belli R, Trinchero R, et al. Efficacy and safety of colchicine for pericarditis prevention. Systematic review and meta-analysis. Heart. 2012;98(14):1078–82.

    CAS  PubMed  Google Scholar 

  9. Alabed S, Cabello JB, Irving GJ, Qintar M, Burls A. Colchicine for pericarditis. Cochrane Database Syst Rev. 2014;8:CD010652.

    Google Scholar 

  10. Schwier NC. Pharmacotherapeutic considerations for using colchicine to treat idiopathic pericarditis in the USA. Am J Cardiovasc Drugs. 2015;15(5):295–306.

    CAS  PubMed  Google Scholar 

  11. Chaldakov GN. Colchicine, a microtubule-disassembling drug, in the therapy of cardiovascular diseases. Cell Biol Int. 2018;42(8):1079–84.

    PubMed  Google Scholar 

  12. Lilly LS. Treatment of acute and recurrent idiopathic pericarditis. Circulation. 2013;127(16):1723–6.

    PubMed  Google Scholar 

  13. Lotrionte M, Biondi-Zoccai G, Imazio M, Castagno D, Moretti C, Abbate A, et al. International collaborative systematic review of controlled clinical trials on pharmacologic treatments for acute pericarditis and its recurrences. Am Heart J. 2010;160(4):662–70.

    CAS  PubMed  Google Scholar 

  14. Wamboldt R, Bisleri G, Glover B, Haseeb S, Tse G, Liu T, et al. Primary prevention of post-pericardiotomy syndrome using corticosteroids: a systematic review. Expert Rev Cardiovasc Ther. 2018;16(6):405–12.

    CAS  PubMed  Google Scholar 

  15. Imazio M, Brucato A, Markel G, Cemin R, Trinchero R, Spodick DH, et al. Meta-analysis of randomized trials focusing on prevention of the postpericardiotomy syndrome. Am J Cardiol. 2011;108(4):575–9.

    PubMed  Google Scholar 

  16. Imazio M, Trinchero R, Brucato A, Rovere ME, Gandino A, Cemin R, et al. COlchicine for the Prevention of the Post-pericardiotomy Syndrome (COPPS): a multicentre, randomized, double-blind, placebo-controlled trial. Eur Heart J. 2010;31(22):2749–54.

    CAS  PubMed  Google Scholar 

  17. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195–207.

    CAS  PubMed  Google Scholar 

  18. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12):1119–31.

    CAS  PubMed  Google Scholar 

  19. Libby P, Everett BM. Novel antiatherosclerotic therapies. Arterioscler Thromb Vasc Biol. 2019;39(4):538–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Nguyen MT, Fernando S, Schwarz N, Tan JT, Bursill CA, Psaltis PJ. Inflammation as a therapeutic target in atherosclerosis. J Clin Med. 2019;8(8):E1109.

    PubMed  Google Scholar 

  21. 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.

    CAS  PubMed  Google Scholar 

  22. 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.

    PubMed  PubMed Central  Google Scholar 

  23. Vaidya K, Martinez G, Patel S. The role of colchicine in acute coronary syndromes. Clin Ther. 2019;41(1):11–20.

    CAS  PubMed  Google Scholar 

  24. Khan R, Spagnoli V, Tardif JC, L’Allier PL. Novel anti-inflammatory therapies for the treatment of atherosclerosis. Atherosclerosis. 2015;240(2):497–509.

    CAS  PubMed  Google Scholar 

  25. Thompson PL, Nidorf SM. Colchicine: an affordable anti-inflammatory agent for atherosclerosis. Curr Opin Lipidol. 2018;29(6):467–73.

    CAS  PubMed  Google Scholar 

  26. Kajikawa M, Higashi Y, Tomiyama H, Maruhashi T, Kurisu S, Kihara Y, et al. Effect of short-term colchicine treatment on endothelial function in patients with coronary artery disease. Int J Cardiol. 2019;281:35–9.

    PubMed  Google Scholar 

  27. Gasparyan AY, Ayvazyan L, Yessirkepov M, Kitas GD. Colchicine as an anti-inflammatory and cardioprotective agent. Expert Opin Drug Metab Toxicol. 2015;11(11):1781–94.

    CAS  PubMed  Google Scholar 

  28. Fiolet ATL, Nidorf SM, Mosterd A, Cornel JH. Colchicine in stable coronary artery disease. Clin Ther. 2019;41(1):30–40.

    CAS  PubMed  Google Scholar 

  29. Verma S, Eikelboom JW, Nidorf SM, Al-Omran M, Gupta N, Teoh H, et al. Colchicine in cardiac disease: a systematic review and meta-analysis of randomized controlled trials. BMC Cardiovasc Disord. 2015;15:96.

    PubMed  PubMed Central  Google Scholar 

  30. Giannopoulos G, Angelidis C, Kouritas VK, Dedeilias P, Filippatos G, Cleman MW, et al. Usefulness of colchicine to reduce perioperative myocardial damage in patients who underwent on-pump coronary artery bypass grafting. Am J Cardiol. 2015;115(10):1376–81.

    CAS  PubMed  Google Scholar 

  31. Hemkens LG, Ewald H, Gloy VL, Arpagaus A, Olu KK, Nidorf M, et al. Colchicine for prevention of cardiovascular events. Cochrane Database Syst Rev. 2016;1:CD011047.

    Google Scholar 

  32. O’Herron T, Lafferty J. Prophylactic use of colchicine in preventing radiation induced coronary artery disease. Med Hypotheses. 2018;111:58–60.

    PubMed  Google Scholar 

  33. Tong DC, Wilson AM, Layland J. Colchicine in cardiovascular disease: an ancient drug with modern tricks. Heart. 2016;102(13):995–1002.

    CAS  PubMed  Google Scholar 

  34. Kottoor SJ, Arora RR. The utility of anti-inflammatory agents in cardiovascular disease: a novel perspective on the treatment of atherosclerosis. J Cardiovasc Pharmacol Ther. 2018;23(6):483–93.

    CAS  PubMed  Google Scholar 

  35. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Nidorf M, Thompson PL. Effect of colchicine (0.5 mg twice daily) on high-sensitivity C-reactive protein independent of aspirin and atorvastatin in patients with stable coronary artery disease. Am J Cardiol. 2007;99(6):805–7.

    CAS  PubMed  Google Scholar 

  37. Hennessy T, Soh L, Bowman M, Kurup R, Schultz C, Patel S, et al. The Low Dose Colchicine after Myocardial Infarction (LoDoCo-MI) study: a pilot randomized placebo controlled trial of colchicine following acute myocardial infarction. Am Heart J. 2019;215:62–9.

    CAS  PubMed  Google Scholar 

  38. Langevitz P, Livneh A, Neumann L, Buskila D, Shemer J, Amolsky D, et al. Prevalence of ischemic heart disease in patients with familial Mediterranean fever. Isr Med Assoc J. 2001;3(1):9–12.

    CAS  PubMed  Google Scholar 

  39. Crittenden DB, Lehmann RA, Schneck L, Keenan RT, Shah B, Greenberg JD, et al. Colchicine use is associated with decreased prevalence of myocardial infarction in patients with gout. J Rheumatol. 2012;39(7):1458–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Slobodnick A, Shah B, Krasnokutsky S, Pillinger MH. Update on colchicine, 2017. Rheumatology (Oxford). 2018;57(suppl_1):i4–11.

    CAS  Google Scholar 

  41. Arbel Y, Abuzeid W, Rosenson RS, Weisman A, Farkouh ME. Old drugs for new indications in cardiovascular medicine. Cardiovasc Drugs Ther. 2018;32(2):223–32.

    CAS  PubMed  Google Scholar 

  42. Spartalis M, Spartalis E, Tzatzaki E, Tsilimigras DI, Moris D, Kontogiannis C, et al. The beneficial therapy with colchicine for atherosclerosis via anti-inflammation and decrease in hypertriglyceridemia. Cardiovasc Hematol Agents Med Chem. 2018;16(2):74–80.

    CAS  PubMed  Google Scholar 

  43. 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.

    CAS  PubMed  Google Scholar 

  44. Akodad M, Fauconnier J, Sicard P, Huet F, Blandel F, Bourret A, et al. Interest of colchicine in the treatment of acute myocardial infarct responsible for heart failure in a mouse model. Int J Cardiol. 2017;240:347–53.

    PubMed  Google Scholar 

  45. Bakhta O, Blanchard S, Guihot AL, Tamareille S, Mirebeau-Prunier D, Jeannin P, et al. Cardioprotective role of colchicine against inflammatory injury in a rat model of acute myocardial infarction. J Cardiovasc Pharmacol Ther. 2018;23(5):446–55.

    CAS  PubMed  Google Scholar 

  46. Emerging Risk Factors Consortium, Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010;375(9709):132–40.

    Google Scholar 

  47. Khandkar C, Vaidya K, Patel S. Colchicine for stroke prevention: a systematic review and meta-analysis. Clin Ther. 2019;41(3):582–590.e3.

    CAS  PubMed  Google Scholar 

  48. Tsivgoulis G, Katsanos AH, Giannopoulos G, Panagopoulou V, Jatuzis D, Lemmens R, et al. The role of colchicine in the prevention of cerebrovascular ischemia. Curr Pharm Des. 2018;24(6):668–74.

    CAS  PubMed  Google Scholar 

  49. Bessissow A, Agzarian J, Shargall Y, Srinathan S, Neary J, Tandon V, et al. Colchicine for prevention of perioperative atrial fibrillation in patients undergoing lung resection surgery: a pilot randomized controlled study. Eur J Cardiothorac Surg. 2018;53(5):945–51.

    PubMed  Google Scholar 

  50. Barman M, Tantawy M, Sopher M, Lennerz C. Cost-effectiveness of colchicine treatment on post-operative atrial fibrillation events in patients of major cardiac surgery. Eur Heart J Qual Care Clin Outcomes. 2018;4(2):126–31.

    PubMed  Google Scholar 

  51. Lennerz C, Barman M, Tantawy M, Sopher M, Whittaker P. Colchicine for primary prevention of atrial fibrillation after open-heart surgery: systematic review and meta-analysis. Int J Cardiol. 2017;249:127–37.

    PubMed  Google Scholar 

  52. Trivedi C, Sadadia M. Colchicine in prevention of atrial fibrillation following cardiac surgery: systematic review and meta-analysis. Indian J Pharmacol. 2014;46(6):590–5.

    PubMed  PubMed Central  Google Scholar 

  53. Anti-inflammatory Effects of Colchicine in PCI: NCT01709981. https://clinicaltrials.gov/ct2/show/NCT01709981.

  54. Colchicine in Percutaneous Coronary Intervention (Colchicine-PCI): NCT02594111. https://clinicaltrials.gov/ct2/show/NCT02594111.

  55. Colchicine and Spironolactone in Patients With STEMI/SYNERGY Stent Registry (CLEAR-SYNERGY): NCT03048825. https://clinicaltrials.gov/ct2/show/NCT03048825.

  56. Colchicine Cardiovascular Outcomes Trial (COLCOT): NCT02551094. https://clinicaltrials.gov/ct2/show/NCT02551094.

  57. Montreal Heart Institute. AHA: COLCOT clinical trial demonstrates it is possible to reduce risk of CV events with los-cost drug already available; 2019. https://www.cathlabdigest.com/content/aha-colcot-clinical-trial-demonstrates-it-possible-reduce-risk-cv-events-low-cost-drug-already-available.

  58. 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.

    CAS  PubMed  Google Scholar 

  59. Levitt G. Colchicine prices are a rip off in America: why? How: Dec 9, 2016. https://www.pharmacycheckerblog.com/colchicine-prices-are-a-rip-off-in-america-why-how.

  60. Kesselheim AS, Franklin JM, Kim SC, Seeger JD, Solomon DH. Reductions in use of colchicine after FDA enforcement of market exclusivity in a commercially insured population. J Gen Intern Med. 2015;30(11):1633–8.

    PubMed  PubMed Central  Google Scholar 

  61. Anderson L. Drug prices gone wild; 10 old drugs, 10 new price tags Apr 23, 2019. https://www.drugs.com/slideshow/old-drugs-new-pricetag-1206.

  62. Medani S, Wall C. Colchicine toxicity in renal patients—are we paying attention? Clin Nephrol. 2016;86(2):100–5.

    CAS  PubMed  Google Scholar 

  63. Solak Y, Atalay H, Biyik Z, Alibasic H, Gaipov A, Guney F, et al. Colchicine toxicity in end-stage renal disease patients: a case-control study. Am J Ther. 2014;21(6):e189–95.

    PubMed  Google Scholar 

  64. Wason S, Mount D, Faulkner R. Single-dose, open-label study of the differences in pharmacokinetics of colchicine in subjects with renal impairment, including end-stage renal disease. Clin Drug Investig. 2014;34(12):845–55.

    CAS  PubMed  Google Scholar 

  65. Eleftheriou G, Bacis G, Fiocchi R, Sebastiano R. Colchicine-induced toxicity in a heart transplant patient with chronic renal failure. Clin Toxicol (Phila). 2008;46(9):827–30.

    CAS  Google Scholar 

  66. Amanova A, Kendi Celebi Z, Bakar F, Caglayan MG, Keven K. Colchicine levels in chronic kidney diseases and kidney transplant recipients using tacrolimus. Clin Transpl. 2014;28(10):1177–83.

    CAS  Google Scholar 

  67. Montseny JJ, Meyrier A, Gherardi RK. Colchicine toxicity in patients with chronic renal failure. Nephrol Dial Transpl. 1996;11(10):2055–8.

    CAS  Google Scholar 

  68. Todd BA, Billups SJ, Delate T, Canty KE, Kauffman AB, Rawlings JE, et al. Assessment of the association between colchicine therapy and serious adverse events. Pharmacotherapy. 2012;32(11):974–80.

    CAS  PubMed  Google Scholar 

  69. Solak Y, Acikgoz SB, Yildirim M. Colchicine toxicity: an exaggerated reality? Am J Med. 2015;128(8):e11.

    PubMed  Google Scholar 

  70. Justiniano M, Dold S, Espinoza LR. Rapid onset of muscle weakness (rhabdomyolysis) associated with the combined use of simvastatin and colchicine. J Clin Rheumatol. 2007;13(5):266–8.

    PubMed  Google Scholar 

  71. Colchicine: serious interactions. Prescrire Int. 2008;17(96):151–3.

  72. Kim S, Jung ES, Lee J, Heo NJ, Na KY, Han JS. Effects of colchicine on renal fibrosis and apoptosis in obstructed kidneys. Korean J Intern Med. 2018;33(3):568–76.

    CAS  PubMed  Google Scholar 

  73. Penchas S, Charuzi I, Boss JH. Beneficial effects of colchicine in experimental nephrotoxic serum nephritis in the rat. Eur J Clin Investig. 1979;9(2 Pt 1):161–6.

    CAS  Google Scholar 

  74. Borras-Blasco J, Enriquez R, Sirvent AE, Amoros F, Navarro-Ruiz A, Reyes A. Acute renal failure associated with an accidental overdose of colchicine. Int J Clin Pharmacol Ther. 2005;43(10):480–4.

    CAS  PubMed  Google Scholar 

  75. Chen HW, Chen KC, Chen JS. Colchicine and NSAID combination causing acute kidney injury. J Coll Physicians Surg Pak. 2012;22(11):737–9.

    PubMed  Google Scholar 

  76. Huang WH, Hsu CW, Yu CC. Colchicine overdose-induced acute renal failure and electrolyte imbalance. Ren Fail. 2007;29(3):367–70.

    PubMed  Google Scholar 

  77. Solak Y, Siriopol D, Yildiz A, Yilmaz MI, Ortiz A, Covic A, et al. Colchicine in renal medicine: new virtues of an ancient friend. Blood Purif. 2017;43(1–3):125–35.

    CAS  PubMed  Google Scholar 

  78. Finkelstein Y, Aks SE, Hutson JR, Juurlink DN, Nguyen P, Dubnov-Raz G, et al. Colchicine poisoning: the dark side of an ancient drug. Clin Toxicol (Phila). 2010;48(5):407–14.

    CAS  Google Scholar 

  79. Ozdogan H, Ugurlu S. Familial Mediterranean fever. Presse Med. 2019;48(1 Pt 2):e61–76.

    PubMed  Google Scholar 

  80. Gallizzi R, Pidone C, Cantarini L, Finetti M, Cattalini M, Filocamo G, et al. A national cohort study on pediatric Behcet’s disease: cross-sectional data from an Italian registry. Pediatr Rheumatol Online J. 2017;15(1):84.

    PubMed  PubMed Central  Google Scholar 

  81. Libby P. Molecular bases of the acute coronary syndromes. Circulation. 1995;91(11):2844–50.

    CAS  PubMed  Google Scholar 

  82. Whayne TF Jr. Is there an ideal low-density lipoprotein cholesterol level? Confusion regarding lipid guidelines, low-density lipoprotein cholesterol targets, and medical management. Int J Angiol. 2017;26(2):73–7.

    PubMed  Google Scholar 

Download references

Acknowledgements

The author thanks Colleen McMullen, MA, MBA, for her excellent editorial critique.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thomas F. Whayne Jr..

Ethics declarations

Funding

No external funding was used in the preparation of this manuscript.

Conflict of Interest

T. F. Whayne, Jr., has no potential conflicts of interest that might be relevant to the contents of this manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Whayne, T.F. Inflammation May be the Future of Cardiovascular Risk Reduction: Does Colchicine have a Current Indication?. Am J Cardiovasc Drugs 21, 1–10 (2021). https://doi.org/10.1007/s40256-020-00408-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40256-020-00408-y

Navigation