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Effect of colchicine compared with placebo on high sensitivity C-reactive protein in patients with acute coronary syndrome or acute stroke: a pilot randomized controlled trial

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Abstract

There is a need for more effective therapies to reduce morbidity and mortality from cardiovascular disease. Inflammation plays a central role in the pathogenesis of atherosclerosis but no randomized studies have evaluated anti-inflammatory therapy in patients with acute coronary or cerebrovascular disease. We performed a pilot randomized controlled trial comparing the effect of colchicine 1 mg per day with placebo on high sensitivity C-reactive protein (CRP) levels and platelet function in 80 patients with acute coronary syndrome or acute ischemic stroke who were followed for 30 days. Clinical status was ascertained for 74 (92.5%) patients and CRP levels were obtained in 68 (85%) of patients at follow up. Colchicine did not significantly reduce absolute hs-CRP at 30 days [median 1.0 mg/l (range 0.2, 162.0) versus 1.5 mg/l (0.2, 19.8), P = 0.22] or difference in CRP from baseline to 30 days [absolute difference 7.0 mg/l (−61.0, 87.8) vs. 7.1 mg/l (−1.0, 144), P = 0.64]. The proportion of patients with CRP <2 mg/l at follow up did not differ according to treatment allocation (77% vs. 62%, X 2 1.84, P = 0.18). There was also no difference in platelet function assessed using platelet aggregation with ADP (5 μmol), arachidonic acid (0.5 mmol), collagen (1 μg/ml) and collagen (5 μg/ml) (P = 0.86, P = 0.64, P = 0.76, P = 0.20, respectively), and urine dehydrothromboxane B2 (P = 0.54). Colchicine was associated with an excess of diarrhoea (X 2 4.14, P = 0.04). In conclusion, our pilot study provided no evidence that colchicine 1 mg daily for 30 days compared with placebo suppresses inflammation in patients with acute coronary syndrome or acute ischemic stroke.

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References

  1. WHO (2010) WHO global burden of disease. http://www.who.int/mediacentre/factsheets/fs317/en/index.html. Accessed 25 July 2010

  2. Libby P (2001) What have we learned about the biology of atherosclerosis? The role of inflammation. Am J Cardiol 88:3J–6J

    PubMed  CAS  Google Scholar 

  3. Virmani R, Burke AP, Farb A, Kolodgie FD (2006) Pathology of the vulnerable plaque. J Am Coll Cardiol 47(C):13–18

    Article  Google Scholar 

  4. Abbate A, Biondi-Zoccai GG, Brugaletta S, Liuzzo G, Biasucci LM (2003) hs-CRP and other inflammatory biomarkers as predictors of outcome following acute coronary syndromes. Semin Vasc Med 4:375–382

    Google Scholar 

  5. Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH, Pfeffer MA, Braunwald E (2005) C-reactive protein levels and outcomes after statin therapy. N Engl J Med 352:20–28

    Article  PubMed  CAS  Google Scholar 

  6. Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L (2000) Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC study group. Fragmin during instability in coronary artery disease. N Engl J Med 343:1139–1147

    Article  PubMed  CAS  Google Scholar 

  7. Rader DJ (2000) Inflammatory markers of coronary risk. Editor N Engl J Med 343:1179–1182

    Article  CAS  Google Scholar 

  8. Buckley DI, Fu R, Freeman M, Rogers K, Helfand M (2009) C-reactive protein as a risk factor for coronary heart disease: a systematic review and meta-analyses for the U.S. preventive services task force. Ann Intern Med 151:483–495

    PubMed  Google Scholar 

  9. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Loerenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ, JUPITER Study Group (2008) Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 359:2195–2207

    Article  PubMed  CAS  Google Scholar 

  10. Perico N, Ostermann D, Bontempeill M, Morigi M, Amuchastegui CS, Zoja C, Akalin E, Sayegh MH, Remuzzi G (1996) Colchicine interferes with L-selectin and leucocyte function associated antigen-1 expression on human T lymphocytes. J Am Soc Nephrol 7:594–601

    PubMed  CAS  Google Scholar 

  11. Cerquaglia C, Diaco M, Nucera G, Regina ML, Montalto M, Manna R (2005) Pharmacological and clinical basis of treatment of familial mediterranean fever (FMF) with colchicine or analogues: an update. Curr Drug Targ Inflamm Allergy 4:117–124

    Article  CAS  Google Scholar 

  12. Wesley RB II, Meng X, Godin D, Galis ZS (1998) Extracellular matrix modulates macrophage functions characteristic to atheroma: collagen type I enhances acquisition of resident macrophage traits by human peripheral blood monocytes in vitro. Arterioscler Thromb Vasc Biol 18:432–440

    Article  PubMed  CAS  Google Scholar 

  13. Chao FC, Shepro D, Tullis JL, Belamarich FA, Curby WA (1976) Similarities between platelet contraction and cellular motility during mitosis: role of platelet microtubules in clot retraction. J Cell Sci 20:569–588

    PubMed  CAS  Google Scholar 

  14. Sneddon JM (1971) Effect of mitosis inhibitors on blood platelet microtubules and aggregation. J Physiol 214:145–158

    PubMed  CAS  Google Scholar 

  15. Nidorf M, Thompson PL (2007) Effect of colchicine (0.5 mg twice daily) on hs-CRP independent of aspirin and atorvastatin in patients with stable coronary artery disease. Am J Cardiol 99:805–807

    Article  PubMed  CAS  Google Scholar 

  16. Molad Y (2002) Update on colchicine and Its mechanism of action. Curr Rheumatol Rep 4:252–256

    Article  PubMed  Google Scholar 

  17. LoDoCo Study (2011) The effect of low-dose colchicine on the natural history of patients with coronary disease. http://apps.who.int/trialsearch/trial.aspx?trialid=ACTRN12610000293066. Accessed 23 August 2011

  18. AtheroGenics (2006) ARISE—aggressive reduction of inflammation stops events. http://clinicaltrials.gov/ct2/show/NCT00066898?term=succinobucol&rank=2. Accessed 10 November 2010

  19. Joslin Diabetes Center (2010) Targeting inflammation using salsalate in cardiovascular disease (TINSAL-CVD). http://www.clinicaltrials.gov/ct2/show/NCT00624923?term=salsalate&rank=3. Accessed 10 November 2010

  20. VIA Pharmaceuticals (2010) Phase 2 study in vascular inflammation on patients after an acute coronary syndrome event. http://www.clinicaltrials.gov/ct2/show/NCT00552188?term=VIA+2291&rank=3. Accessed 10 November 2010

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Correspondence to Nina C. Raju.

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Raju, N.C., Yi, Q., Nidorf, M. et al. Effect of colchicine compared with placebo on high sensitivity C-reactive protein in patients with acute coronary syndrome or acute stroke: a pilot randomized controlled trial. J Thromb Thrombolysis 33, 88–94 (2012). https://doi.org/10.1007/s11239-011-0637-y

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