Consistent CV benefit of colchicine in patients with coronary disease

Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials

Literature - Fiolet ATL, Opstal TSJ, Mosterd A et al., - Eur Heart J 2021, doi:10.1093/eurheartj/ehab115

Introduction and methods

Recent trials demonstrated that use of colchicine resulted in reduction of major adverse cardiovascular events (MACE) in patient with coronary disease [1,2]. Potential mechanisms of benefit observed with colchicine include inhibition of inflammasome activation; inhibition of neutrophil chemotaxis, adhesion and activation; and inhibition of neutrophil-platelet interaction [3-5].

A systematic review and meta-analysis of randomized trials was performed to assess the overall effect of colchicine on MACE and individual end points in patients with acute or chronic coronary disease.

Eligible studies compared the efficacy of long-term colchicine treatment (≥3 months) with standard treatment with or without placebo in a patient population with established atherosclerosis. The pre-specified primary endpoint of this meta-analysis was the composite of MI, stroke, or CV death. 5 Trials were included, involving 11,816 patients randomized to colchicine (n=5918) or placebo or standard treatment (n=5898). 46.9% Of patients were enrolled within 30 days of acute coronary syndrome and 51.3% of patients had chronic coronary disease.

Main results

  • Colchicine reduced risk for the primary endpoint of MACE by 25% (RR 0.75; 95%CI: 0.61-0.92, P=0.005, with low heterogeneity, I2=23.9%).
  • Key secondary endpoint of MI, stroke, coronary revascularization or CV death was reduced by 33% in the colchicine-group (RR 0.67; 95%CI: 0.55-0.82, P<0.001).
  • There was no significant interaction between treatment and acute coronary syndrome or chronic coronary disease for the primary or the secondary endpoint.
  • NNT for the composite of MI, stroke, coronary revascularization or CV death varied from 30 to 98 patients for 1 year with a weighted-average estimate of 84 and from 9 to 60 for 3 years with a weighted-average estimate of 40.
  • Colchicine reduced the risk for MI by 22% (RR 0.78, 95%CI: 0.64-0.94, P=0.01), for stroke by 46% (RR 0.54, 95%CIL 0.34-0.86, P=0.009) and for coronary revascularization by 23% (RR 0.77, 95%CI: 0.66-090, P<0.001).
  • No difference was observed for all-cause death, with a non-significant lower risk of CV death (RR 0.82, 95%CI: 0.55-1.23, P=0.339) and a non-significant high risk of non-CV death (RR 1.38, 95%CIL 0.99-1.92, P=0.060) in the colchicine-group.
  • Colchicine was not associated with increased risk for hospitalization for infection in general, or hospitalization for pneumonia, hospitalization for gastro-intestinal disorders or risk for new cancer.


This meta-analysis of 5 trials evaluating the effect of low-dose colchicine showed that colchicine reduced MACE and individual CV endpoints compared to placebo or no colchicine in patients with acute and chronic coronary disease when added to contemporary treatment.


1. Tardif J-C, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, Pinto FJ, Ibrahim R, Gamra H, Kiwan GS, Berry C, Lo´pez-Sendo´n J, Ostadal P, Koenig W, Angoulvant D, Gre´goire JC, Lavoie M-A, Dube´ M-P, Rhainds D, Provencher M, Blondeau L, Orfanos A, L’Allier PL, Guertin M-C, Roubille F. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med 2019;381: 2497–2505.

2. Nidorf SM, Fiolet ATL, Mosterd A, Eikelboom JW, Schut A, Opstal TSJ, The SHK, Xu XF, Ireland MA, Lenderink T, Latchem D, Hoogslag P, Jerzewski A, Nierop P, Whelan A, Hendriks R, Swart H, Schaap J, Kuijper AFM, van Hessen

MWJ, Saklani P, Tan I, Thompson AG, Morton A, Judkins C, Bax WA, Dirksen M, Alings M, Hankey GJ, Budgeon CA, Tijssen JGP, Cornel JH, Thompson PL, LoDoCo2 Trial Investigators. Colchicine in patients with chronic coronary disease. N Engl J Med 2020;383:1838–1847.

3. Nuki G. Colchicine: its mechanism of action and efficacy in crystal-induced inflammation. Curr Rheumatol Rep 2008;10:218–227.

4. Leung YY, Yao Hui LL, Kraus VB. Colchicine—update on mechanisms of action and therapeutic uses. Semin Arthritis Rheum 2015;45:341–350.

5. Opstal TSJ, Hoogeveen RM, Fiolet ATL, Silvis MJM, The SHK, Bax WA, de Kleijn DPV, Mosterd A, Stroes ESG, Cornel JH. Colchicine attenuates inflammation beyond the inflammasome in chronic coronary artery disease: a LoDoCo2 proteomic substudy. Circulation 2020;142:1996–1998.

Find this article online at Eur Heart J

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