Advertisement

Usefulness of Colchicine to Reduce Perioperative Myocardial Damage in Patients Who Underwent On-Pump Coronary Artery Bypass Grafting

Published:February 19, 2015DOI:https://doi.org/10.1016/j.amjcard.2015.02.036
      The objective of the present study was to test whether a perioperative course of colchicine, in patients who underwent standard coronary artery bypass grafting, would result in reduced postoperative increase of myocardial injury biomarker levels. Patients were prospectively randomized to colchicine or placebo starting 48 hours before scheduled coronary artery bypass grafting and for 8 days thereafter (0.5 mg twice daily). The primary outcome parameter was maximal high-sensitivity troponin T (hsTnT) concentration within 48 hours after surgery. Secondary outcome measures were maximal creatine kinase-myocardial brain fraction (CK-MB) levels and area under the curve (AUC) of hsTnT and CK-MB concentrations; 59 patients were included. Maximal hsTnT was 616 pg/ml (396 to 986) in the colchicine group versus 1,613 pg/ml (732 to 2,587) in controls (p = 0.002). Maximal CK-MB was 44.6 ng/ml (36.6 to 68.8) and 93.0 ng/ml (48.0 to 182.3), respectively (p = 0.002). The median AUC for hsTnT was 40,755 pg h/ml (20,868 to 79,176) in controls versus 20,363 pg h/ml (13,891 to 31,661) in the colchicine group (p = 0.002). AUCs for CK-MB were 2,552 ng h/ml (1,564 to 4,791) in controls and 1,586 ng h/ml (1,159 to 2,073) in the colchicine group (p = 0.003). The main complaints associated with colchicine were, as expected, gastrointestinal, with 5 patients (16.7%) in the colchicine group reporting diarrhea versus 1 control (3.4%) (p = 0.195). In conclusion, a short perioperative course of colchicine was effective in attenuating postoperative increases of hsTnT and CK-MB compared with placebo. This finding, which needs confirmation in a larger clinical trial powered to assess clinical endpoints, suggests a potential role for this agent in reducing cardiac surgery–related myocardial damage.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Boyle E.M.
        • Pohlman T.H.
        • Johnson M.C.
        • Verrier E.D.
        Endothelial cell injury in cardiovascular surgery: the systemic inflammatory response.
        Ann Thorac Surg. 1997; 63: 277-284
        • Miller B.E.
        • Levy J.H.
        The inflammatory response to cardiopulmonary bypass.
        J Cardiothorac Vasc Anesth. 1997; 11: 355-366
        • Costa M.A.
        • Carere R.G.
        • Lichtenstein S.V.
        • Foley D.P.
        • de Valk V.
        • Lindenboom W.
        • Roose P.C.
        • van Geldorp T.R.
        • Macaya C.
        • Castanon J.L.
        • Fernandez-Avilèz F.
        • Gonzáles J.H.
        • Heyer G.
        • Unger F.
        • Serruys P.W.
        Incidence, predictors, and significance of abnormal cardiac enzyme rise in patients treated with bypass surgery in the arterial revascularization therapies study (ARTS).
        Circulation. 2001; 104: 2689-2693
        • Klatte K.
        • Chaitman B.R.
        • Theroux P.
        • Gavard J.A.
        • Stocke K.
        • Boyce S.
        • Bartels C.
        • Keller B.
        • Jessel A.
        GUARDIAN Investigators. Increased mortality after coronary artery bypass graft surgery is associated with increased levels of postoperative creatine kinase-myocardial band isoenzyme release: results from the GUARDIAN trial.
        J Am Coll Cardiol. 2001; 38: 1070-1077
        • Croal B.L.
        • Hillis G.S.
        • Gibson P.H.
        • Fazal M.T.
        • El-Shafei H.
        • Gibson G.
        • Jeffrey R.R.
        • Buchan K.G.
        • West D.
        • Cuthbertson B.H.
        Relationship between postoperative cardiac troponin I levels and outcome of cardiac surgery.
        Circulation. 2006; 114: 1468-1475
        • Januzzi J.L.
        • Lewandrowski K.
        • MacGillivray T.E.
        • Newell J.B.
        • Kathiresan S.
        • Servoss S.J.
        • Lee-Lewandrowski E.
        A comparison of cardiac troponin T and creatine kinase-MB for patient evaluation after cardiac surgery.
        J Am Coll Cardiol. 2002; 39: 1518-1523
        • Paparella D.
        • Cappabianca G.
        • Visicchio G.
        • Galeone A.
        • Marzovillo A.
        • Gallo N.
        • Memmola C.
        • Schinosa Lde L.
        Cardiac troponin I release after coronary artery bypass grafting operation: effects on operative and midterm survival.
        Ann Thorac Surg. 2005; 80: 1758-1764
        • Lurati Buse G.A.
        • Bolliger D.
        • Seeberger E.
        • Kasper J.
        • Grapow M.
        • Koller M.T.
        • Seeberger M.D.
        • Filipovic M.
        Troponin T and brain natriuretic peptide after on-pump cardiac surgery: prognostic impact on 12-month mortality and major cardiac events after adjustment for postoperative complications.
        Circulation. 2014; 130: 948-957
        • Lim C.C.
        • Cuculi F.
        • van Gaal W.J.
        • Testa L.
        • Arnold J.R.
        • Karamitsos T.
        • Francis J.M.
        • Digby J.E.
        • Antoniades C.
        • Kharbanda R.K.
        • Neubauer S.
        • Westaby S.
        • Banning A.P.
        Early diagnosis of perioperative myocardial infarction after coronary bypass grafting: a study using biomarkers and cardiac magnetic resonance imaging.
        Ann Thorac Surg. 2011; 92: 2046-2053
        • Jain U.
        Myocardial infarction during coronary artery bypass surgery.
        J Cardiothorac Vasc Anesth. 1992; 6: 612-623
        • Rasmussen C.
        • Thiis J.J.
        • Clemmensen P.
        • Efsen F.
        • Arendrup H.C.
        • Saunamäki K.
        • Madsen J.K.
        • Pettersson G.
        Significance and management of early graft failure after coronary artery bypass grafting: feasibility and results of acute angiography and re-vascularization.
        Eur J Cardiothorac Surg. 1997; 12: 847-852
        • Butler J.
        • Rocker G.M.
        • Westaby S.
        Inflammatory response to cardiopulmonary bypass.
        Ann Thorac Surg. 1993; 55: 552-559
        • Ascione R.
        • Lloyd C.T.
        • Underwood M.J.
        • Lotto A.A.
        • Pitsis A.A.
        • Angelini G.D.
        Inflammatory response after coronary revascularization with or without cardiopulmonary bypass.
        Ann Thorac Surg. 2000; 69: 1198-1204
        • Raja S.G.
        • Dreyfus G.D.
        Modulation of systemic inflammatory response after cardiac surgery.
        Asian Cardiovasc Thorac Ann. 2005; 13: 382-395
        • Deftereos S.
        • Giannopoulos G.
        • Raisakis K.
        • Kossyvakis C.
        • Kaoukis A.
        • Panagopoulou V.
        • Driva M.
        • Hahalis G.
        • Pyrgakis V.
        • Alexopoulos D.
        • Manolis A.S.
        • Stefanadis C.
        • Cleman M.W.
        Colchicine treatment for the prevention of bare-metal stent restenosis in diabetic patients.
        J Am Coll Cardiol. 2013; 61: 1679-1685
        • Nidorf S.M.
        • Eikelboom J.W.
        • Budgeon C.A.
        • Thompson P.L.
        Low-dose colchicine for secondary prevention of cardiovascular disease.
        J Am Coll Cardiol. 2013; 61: 404-410
        • Deftereos S.
        • Giannopoulos G.
        • Panagopoulou V.
        • Bouras G.
        • Raisakis K.
        • Kossyvakis C.
        • Karageorgiou S.
        • Papadimitriou C.
        • Vastaki M.
        • Kaoukis A.
        • Angelidis C.
        • Pagoni S.
        • Pyrgakis V.
        • Alexopoulos D.
        • Manolis A.S.
        • Stefanadis C.
        • Cleman M.W.
        Anti-inflammatory treatment with colchicine in stable chronic heart failure: a prospective, randomized study.
        J Am Coll Cardiol Heart Fail. 2014; 2: 131-137
        • Deftereos S.
        • Giannopoulos G.
        • Efremidis M.
        • Kossyvakis C.
        • Katsivas A.
        • Panagopoulou V.
        • Papadimitriou C.
        • Karageorgiou S.
        • Doudoumis K.
        • Raisakis K.
        • Kaoukis A.
        • Alexopoulos D.
        • Manolis A.S.
        • Stefanadis C.
        • Cleman M.W.
        Colchicine for prevention of atrial fibrillation recurrence after pulmonary vein isolation: mid-term efficacy and effect on quality of life.
        Heart Rhythm. 2014; 11: 620-628
        • Deftereos S.
        • Giannopoulos G.
        • Papoutsidakis N.
        • Panagopoulou V.
        • Kossyvakis C.
        • Raisakis K.
        • Cleman M.W.
        • Stefanadis C.
        Colchicine and the heart: pushing the envelope.
        J Am Coll Cardiol. 2013; 62: 1817-1825
        • Terkeltaub R.A.
        Colchicine update: 2008.
        Semin Arthritis Rheum. 2009; 38: 411-419
        • Fernandes F.
        • Ramires F.J.
        • Ianni B.M.
        • Salemi V.M.
        • Oliveira A.M.
        • Pessoa F.G.
        • Canzian M.
        • Mady C.
        Effect of colchicine on myocardial injury induced by Trypanosoma cruzi in experimental Chagas disease.
        J Card Fail. 2012; 18: 654-659
        • Cronstein B.N.
        • Molad Y.
        • Reibman J.
        • Balakhane E.
        • Levin R.I.
        • Weissmann G.
        Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils.
        J Clin Invest. 1995; 96: 994-1002
        • Forrat R.
        • Sebbag L.
        • Ferrera R.
        • Hadour G.
        • Canet E.
        • Tabib A.
        • de Lorgeril M.
        Effect of colchicine on circulating and myocardial neutrophils and on infarct size in a canine model of ischemia and reperfusion.
        J Cardiovasc Pharmacol. 1996; 27: 876-883
        • Vinten-Johansen J.
        Involvement of neutrophils in the pathogenesis of lethal myocardial reperfusion injury.
        Cardiovasc Res. 2004; 61: 481-497
        • 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: 274-282
        • Misawa T.
        • Takahama M.
        • Kozaki T.
        • Lee H.
        • Zou J.
        • Saitoh T.
        • Akira S.
        Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome.
        Nat Immunol. 2013; 14: 454-460
        • Kawaguchi M.
        • Takahashi M.
        • Hata T.
        • Kashima Y.
        • Usui F.
        • Morimoto H.
        • Izawa A.
        • Takahashi Y.
        • Masumoto J.
        • Koyama J.
        • Hongo M.
        • Noda T.
        • Nakayama J.
        • Sagara J.
        • Taniguchi S.
        • Ikeda U.
        Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury.
        Circulation. 2011; 123: 594-604
        • Imazio M.
        • Trinchero R.
        • Brucato A.
        • Rovere M.E.
        • Gandino A.
        • Cemin R.
        • Ferrua S.
        • Maestroni S.
        • Zingarelli E.
        • Barosi A.
        • Simon C.
        • Sansone F.
        • Patrini D.
        • Vitali E.
        • Ferrazzi P.
        • Spodick D.H.
        • Adler Y.
        • COPPS Investigators
        Colchicine for the Prevention of the Post-pericardiotomy Syndrome (COPPS): a multicentre, randomized, double-blind, placebo-controlled trial.
        Eur Heart J. 2010; 31: 2749-2754
        • Imazio M.
        • Brucato A.
        • Ferrazzi P.
        • Rovere M.E.
        • Gandino A.
        • Cemin R.
        • Ferrua S.
        • Belli R.
        • Maestroni S.
        • Simon C.
        • Zingarelli E.
        • Barosi A.
        • Sansone F.
        • Patrini D.
        • Vitali E.
        • Trinchero R.
        • Spodick D.H.
        • Adler Y.
        • COPPS Investigators
        Colchicine reduces postoperative atrial fibrillation: results of the Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) atrial fibrillation substudy.
        Circulation. 2011; 124: 2290-2295
        • Imazio M.
        • Brucato A.
        • Ferrazzi P.
        • Pullara A.
        • Adler Y.
        • Barosi A.
        • Caforio A.L.
        • Cemin R.
        • Chirillo F.
        • Comoglio C.
        • Cugola D.
        • Cumetti D.
        • Dyrda O.
        • Ferrua S.
        • Finkelstein Y.
        • Flocco R.
        • Gandino A.
        • Hoit B.
        • Innocente F.
        • Maestroni S.
        • Musumeci F.
        • Oh J.
        • Pergolini A.
        • Polizzi V.
        • Ristic A.
        • Simon C.
        • Spodick D.H.
        • Tarzia V.
        • Trimboli S.
        • Valenti A.
        • Belli R.
        • Gaita F.
        • COPPS-2 Investigators
        Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation: the COPPS-2 randomized clinical trial.
        JAMA. 2014; 312: 1016-1023

      Linked Article

      • Did Colchicine Prove Useful in the Prevention of Postoperative Atrial Fibrillation?
        American Journal of CardiologyVol. 116Issue 1
        • Preview
          Giannopoulos et al1 recently published their work in the AJC, which is of great clinical interest. The investigators showed a significant reduction in myocardial injury (as measured by serum troponin) with the perioperative use of colchicine in patients with stable coronary artery disease undergoing coronary bypass grafting. We especially wonder whether the authors investigated the incidence of early postoperative atrial fibrillation (POAF) in their study. It is an important and easily accountable measure based on their study design.
        • Full-Text
        • PDF
      • The Benefit from Anti-Inflammatory Properties of Colchicine in Cardiovascular Diseases
        American Journal of CardiologyVol. 116Issue 3
        • Preview
          A recent randomized controlled trial by Giannopoulos et al1 demonstrated the benefit from perioperative use of colchicine in patients undergoing elective coronary artery bypass grafting presumably through its anti-inflammatory properties. Maximal high-sensitivity troponin T concentration within 48 hours after the operation was significantly lower in the colchicine group than the placebo group. We were attracted to this interesting cleverly designed trial and the well-written report. However, we intended to point out potential confounders.
        • Full-Text
        • PDF