Advertisement

The Use of Colchicine in Cardiovascular Diseases: A Systematic Review

Published:February 16, 2021DOI:https://doi.org/10.1016/j.amjmed.2021.01.019

      Abstract

      The medicinal properties of colchicine have been recognized for centuries. Although previously used for gout and familial Mediterranean fever, its immune-modulating, anti-inflammatory, and antifibrotic effects are increasingly recognized as beneficial in the treatment of cardiovascular disorders. In this systematic review, we summarize the current evidence on colchicine's effectiveness in 1) pericarditis, 2) coronary artery disease, and 3) atrial fibrillation. We also discuss the safety, potential adverse effects, and common drug interactions that should be considered during use.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      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 The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Graham W
        • Roberts JB
        Intravenous colchicine in the management of gouty arthritis.
        Ann Rheum Dis. 1953; 12: 16-19
        • Roubille F
        • Kritikou E
        • Busseuil D
        • Barrere-Lemaire S
        • Tardif JC
        Colchicine: an old wine in a new bottle?.
        Antiinflamm Antiallergy Agents Med Chem. 2013; 12: 14-23
      1. Prescribing Information for Colchicine. In: FDA, ed. Philadelphia 2009.https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022351lbl.pdf; Last accessed March 2nd, 2021.

        • Deftereos S
        • Giannopoulos G
        • Papoutsidakis N
        • et al.
        Colchicine and the heart: pushing the envelope.
        J Am Coll Cardiol. 2013; 62: 1817-1825
        • Leung YY
        • Yao Hui LL
        • Kraus VB
        Colchicine–Update on mechanisms of action and therapeutic uses.
        Semin Arthritis Rheum. 2015; 45: 341-350
        • Lee FY
        • Lu HI
        • Zhen YY
        • et al.
        Benefit of combined therapy with nicorandil and colchicine in preventing monocrotaline-induced rat pulmonary arterial hypertension.
        Eur J Pharm Sci. 2013; 50: 372-384
        • Akodad M
        • Sicard P
        • Fauconnier J
        • Roubille F
        Colchicine and myocardial infarction: a review.
        Arch Cardiovasc Dis. 2020; 113: 652-659
        • Verma S
        • Eikelboom JW
        • Nidorf SM
        • et al.
        Colchicine in cardiac disease: a systematic review and meta-analysis of randomized controlled trials.
        BMC Cardiovasc Disord. 2015; 15: 96
        • Liberati A
        • Altman DG
        • Tetzlaff J
        • et al.
        The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
        J Clin Epidemiol. 2009; 62: e1-e34
        • Guindo J
        • Rodriguez de la Serna A
        • Ramio J
        • et al.
        Recurrent pericarditis. Relief with colchicine.
        Circulation. 1990; 82: 1117-1120
        • 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. 2005; 165: 1987-1991
        • 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. 2005; 112: 2012-2016
        • Imazio M
        • Cecchi E
        • Ierna S
        • Trinchero R
        • ICAP Investigators
        Investigation on colchicine for acute pericarditis: a multicenter randomized placebo-controlled trial evaluating the clinical benefits of colchicine as adjunct to conventional therapy in the treatment and prevention of pericarditis; study design amd rationale.
        J Cardiovasc Med (Hagerstown). 2007; 8: 613-617
        • Imazio M
        • Brucato A
        • Cemin R
        • et al.
        Colchicine for recurrent pericarditis (CORP): a randomized trial.
        Ann Intern Med. 2011; 155: 409-414
        • 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. 2014; 383: 2232-2237
        • 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. 2015; 36: 2921-2964
        • Lotrionte M
        • Biondi-Zoccai G
        • Imazio M
        • et al.
        International collaborative systematic review of controlled clinical trials on pharmacologic treatments for acute pericarditis and its recurrences.
        Am Heart J. 2010; 160: 662-670
        • Tamarappoo BK
        • Klein AL
        Post-pericardiotomy Syndrome.
        Curr Cardiol Rep. 2016; 18: 116
        • 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. 2010; 31: 2749-2754
        • 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. 2014; 312: 1016-1023
        • Izadi Amoli A
        • Bozorgi A
        • HajHossein Talasaz A
        • et al.
        Efficacy of colchicine versus placebo for the treatment of pericardial effusion after open-heart surgery: a randomized, placebo-controlled trial.
        Am Heart J. 2015; 170: 1195-1201
        • Meurin P
        • Lelay-Kubas S
        • Pierre B
        • et al.
        Colchicine for post-operative pericardial effusion: preliminary results of the POPE-2 study.
        J Am Coll Cardiol. 2015; 66: 1198-1199
        • Paoletti R
        • Gotto Jr., AM
        • Hajjar DP
        Inflammation in atherosclerosis and implications for therapy.
        Circulation. 2004; 109 (III20-III26)
        • Ridker PM
        Testing the inflammatory hypothesis of atherothrombosis: scientific rationale for the cardiovascular inflammation reduction trial (CIRT).
        J Thromb Haemost. 2009; 7: 332-339
        • Moreira DM
        • da Silva RL
        • Vieira JL
        • Fattah T
        • Lueneberg ME
        • Gottschall CA
        Role of vascular inflammation in coronary artery disease: potential of anti-inflammatory drugs in the prevention of atherothrombosis. Inflammation and anti-inflammatory drugs in coronary artery disease.
        Am J Cardiovasc Drugs. 2015; 15: 1-11
        • Angelidis A
        • Račeková E
        • Arnoul P
        • Zavodska M
        • Racek A
        • Martoncikova M
        Disrupted migration and proliferation of neuroblasts after postnatal administration of angiogenesis inhibitor.
        Brain Res. 2018; 1698: 121-129
        • Cimmino G
        • Tarallo R
        • Conte S
        • et al.
        Colchicine reduces platelet aggregation by modulating cytoskeleton rearrangement via inhibition of cofilin and LIM domain kinase 1.
        Vascul Pharmacol. 2018; 111: 62-70
        • Ridker PM
        From C-reactive protein to interleukin-6 to interleukin-1: moving upstream to identify novel targets for atheroprotection.
        Circ Res. 2016; 118: 145-156
        • 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. 2015; 4e002128
        • Nidorf SM
        • Eikelboom JW
        • Budgeon CA
        • Thompson PL
        Low-dose colchicine for secondary prevention of cardiovascular disease.
        J Am Coll Cardiol. 2013; 61: 404-410
        • Nidorf SM
        • Fiolet ATL
        • Mosterd A
        • et al.
        Colchicine in patients with chronic coronary disease.
        N Engl J Med. 2020; 383: 1838-1847
        • Stumpf C
        • Sheriff A
        • Zimmermann S
        • et al.
        C-reactive protein levels predict systolic heart failure and outcome in patients with first ST-elevation myocardial infarction treated with coronary angioplasty.
        Arch Med Sci. 2017; 13: 1086-1093
        • Akodad M
        • Lattuca B
        • Nagot N
        • et al.
        COLIN trial: value of colchicine in the treatment of patients with acute myocardial infarction and inflammatory response.
        Arch Cardiovasc Dis. 2017; 110: 395-402
        • Raju NC
        • Yi Q
        • Nidorf M
        • Fagel ND
        • Hiralal R
        • Eikelboom JW
        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. 2012; 33: 88-94
        • Kajikawa M
        • Higashi Y
        • Tomiyama H
        • et al.
        Effect of short-term colchicine treatment on endothelial function in patients with coronary artery disease.
        Int J Cardiol. 2019; 281: 35-39
        • Vaidya K
        • Arnott C
        • Martinez GJ
        • et al.
        Colchicine therapy and plaque stabilization in patients with acute coronary syndrome: a CT coronary angiography study.
        JACC Cardiovasc Imaging. 2018; 11: 305-316
        • Tardif JC
        • Kouz S
        • Waters DD
        • et al.
        Efficacy and safety of low-dose colchicine after myocardial infarction.
        N Engl J Med. 2019; 381: 2497-2505
        • Tong DC
        • Quinn S
        • Nasis A
        • et al.
        Colchicine in patients with acute coronary syndrome: the Australian COPS randomized clinical trial.
        Circulation. 2020; 142: 1890-1900
        • Schotten U
        • Verheule S
        • Kirchhof P
        • Goette A
        Pathophysiological mechanisms of atrial fibrillation: a translational appraisal.
        Physiol Rev. 2011; 91: 265-325
        • Sovari AA
        Cellular and molecular mechanisms of arrhythmia by oxidative stress.
        Cardiol Res Pract. 2016; 20169656078
        • Arsenault KA
        • Yusuf AM
        • Crystal E
        • et al.
        Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery.
        Cochrane Database Syst Rev. 2013; CD003611
        • Bruins P
        • te Velthuis H
        • Yazdanbakhsh AP
        • et al.
        Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C-reactive protein and is associated with postoperative arrhythmia.
        Circulation. 1997; 96: 3542-3548
        • Hall RI
        • Smith MS
        • Rocker G
        The systemic inflammatory response to cardiopulmonary bypass: pathophysiological, therapeutic, and pharmacological considerations.
        Anesth Analg. 1997; 85: 766-782
        • Sarzaeem M
        • Shayan N
        • Bagheri J
        • Jebelli M
        • Mandegar M
        Low dose colchicine in prevention of atrial fibrillation after coronary artery bypass graft: a double blind clinical trial.
        Tehran University Medical Journal. 2014; 72
        • 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. 2016; 178: 102-107
        • Zarpelon CS
        • Netto MC
        • Jorge JC
        • et al.
        Colchicine to reduce atrial fibrillation in the postoperative period of myocardial revascularization.
        Arq Bras Cardiol. 2016; 107: 4-9
        • Bessissow A
        • Agzarian J
        • Shargall Y
        • 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: 945-951
        • 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: 126-131
        • Zemer D
        • Livneh A
        • Danon YL
        • Pras M
        • Sohar E
        Long-term colchicine treatment in children with familial Mediterranean fever.
        Arthritis Rheum. 1991; 34: 973-977
      2. US Food and Drug Administration. Information for healthcare professionals: new safety information for colchicine (marketed as Colcrys). In: FDA U, ed. Silver Spring 2013.

        • Cirillo P
        • Taglialatela V
        • Pellegrino G
        • et al.
        Effects of colchicine on platelet aggregation in patients on dual antiplatelet therapy with aspirin and clopidogrel.
        J Thromb Thrombolysis. 2020; 50: 468-472
        • Sag E
        • Bayindir Y
        • Adiguzel A
        • et al.
        Colchicine and leukopenia: clinical implications.
        J Pediatr. 2020; 224 (166-170.e1) (Last accessed March 2nd, 2021)
        • Wiggins BS
        • Saseen JJ
        • Page 2nd, RL
        • et al.
        Recommendations for management of clinically significant drug-drug interactions with statins and select agents used in patients with cardiovascular disease: a scientific statement from the American Heart Association.
        Circulation. 2016; 134: e468-e495
        • Terkeltaub RA
        • Furst DE
        • Digiacinto JL
        • Kook KA
        • Davis MW
        Novel evidence-based colchicine dose-reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome P450 3A4/P-glycoprotein inhibitors.
        Arthritis Rheum. 2011; 63: 2226-2237