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      Colchicine in cardiac disease: a systematic review and meta-analysis of randomized controlled trials

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          Abstract

          Background

          Colchicine has unique anti-inflammatory properties that may be beneficial in various cardiovascular conditions. This systematic review and meta-analysis of randomized controlled trials (RCTs) examines this issue.

          Methods

          We searched MEDLINE, EMBASE, and the Cochrane Database from inception to June 2014 for RCTs using colchicine in adult patients with cardiac diseases. Results were pooled using random effects.

          Results

          15 RCTs (n = 3431 patients, median treatment 3 and follow-up 15 months) were included. All but 2 used colchicine 1 mg/day. In 5 trials, n = 1301) at risk for cardiovascular disease (coronary artery disease, acute coronary syndrome or stroke, post-angioplasty [2 RCTs], or congestive heart failure), colchicine reduced composite cardiovascular outcomes by ~60 % (risk ratio [RR] 0.44, 95 % confidence interval [CI] 0.28-0.69, p = 0.0004; I 2 = 0 %) and showed a trend towards lower all-cause mortality (RR 0.50, 95 % CI 0.23-1.08, p = 0.08; I 2 = 0 %). In pericarditis or post-cardiotomy, colchicine decreased recurrent pericarditis or post-pericardiotomy syndrome (RR 0.50, 95 % CI 0.41-0.60, p < 0.0001; I 2 = 0 %; 8 RCTs, n = 1635), and post-pericardiotomy or ablation induced atrial fibrillation (RR 0.65, 95 % CI 0.51-0.82, p = 0.0003; I 2 = 31 %; 4 RCTs, n = 1118). The most common adverse event was diarrhea. Treatment discontinuation overall and due to adverse events (RR 4.34, 95 % CI 1.70-11.07, p = 0.002; I 2 = 29 %; 7 RCTs, 83/790 [10.5 %] vs. 11/697 [1.6 %]) was higher in colchicine-assigned patients.

          Conclusions

          Current RCT data suggests that colchicine may reduce the composite rate of cardiovascular adverse outcomes in a range of patients with established cardiovascular disease. Furthermore, colchicine reduces rates of recurrent pericarditis, post-pericardiotomy syndrome, and peri-procedural atrial fibrillation following cardiac surgery. Further RCTs evaluating the potential of colchicine for secondary prevention of cardiovascular events would be of interest.

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          Most cited references46

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          Low-dose colchicine for secondary prevention of cardiovascular disease.

          The objective of this study was to determine whether colchicine 0.5 mg/day can reduce the risk of cardiovascular events in patients with clinically stable coronary disease. The presence of activated neutrophils in culprit atherosclerotic plaques of patients with unstable coronary disease raises the possibility that inhibition of neutrophil function with colchicine may reduce the risk of plaque instability and thereby improve clinical outcomes in patients with stable coronary disease. In a clinical trial with a prospective, randomized, observer-blinded endpoint design, 532 patients with stable coronary disease receiving aspirin and/or clopidogrel (93%) and statins (95%) were randomly assigned colchicine 0.5 mg/day or no colchicine and followed for a median of 3 years. The primary outcome was the composite incidence of acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke. The primary analysis was by intention-to-treat. The primary outcome occurred in 15 of 282 patients (5.3%) who received colchicine and 40 of 250 patients (16.0%) assigned no colchicine (hazard ratio: 0.33; 95% confidence interval [CI] 0.18 to 0.59; p < 0.001; number needed to treat: 11). In a pre-specified secondary on-treatment analysis that excluded 32 patients (11%) assigned to colchicine who withdrew within 30 days due to intestinal intolerance and a further 7 patients (2%) who did not start treatment, the primary outcome occurred in 4.5% versus 16.0% (hazard ratio: 0.29; 95% CI: 0.15 to 0.56; p < 0.001). Colchicine 0.5 mg/day administered in addition to statins and other standard secondary prevention therapies appeared effective for the prevention of cardiovascular events in patients with stable coronary disease. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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            Optimal search strategies for retrieving scientifically strong studies of treatment from Medline: analytical survey.

            To develop and test optimal Medline search strategies for retrieving sound clinical studies on prevention or treatment of health disorders. Analytical survey. 161 clinical journals indexed in Medline for the year 2000. Sensitivity, specificity, precision, and accuracy of 4862 unique terms in 18 404 combinations. Only 1587 (24.2%) of 6568 articles on treatment met criteria for testing clinical interventions. Combinations of search terms reached peak sensitivities of 99.3% (95% confidence interval 98.7% to 99.8%) at a specificity of 70.4% (69.8% to 70.9%). Compared with best single terms, best multiple terms increased sensitivity for sound studies by 4.1% (absolute increase), but with substantial loss of specificity (absolute difference 23.7%) when sensitivity was maximised. When terms were combined to maximise specificity, 97.4% (97.3% to 97.6%) was achieved, about the same as that achieved by the best single term (97.6%, 97.4% to 97.7%). The strategies newly reported in this paper outperformed other validated search strategies except for two strategies that had slightly higher specificity (98.1% and 97.6% v 97.4%) but lower sensitivity (42.0% and 92.8% v 93.1%). New empirical search strategies have been validated to optimise retrieval from Medline of articles reporting high quality clinical studies on prevention or treatment of health disorders.
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              A randomized trial of colchicine for acute pericarditis.

              Colchicine is effective for the treatment of recurrent pericarditis. However, conclusive data are lacking regarding the use of colchicine during a first attack of acute pericarditis and in the prevention of recurrent symptoms.
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                Author and article information

                Contributors
                1-416-864-5997 , vermasu@smh.ca
                eikelbj@mcmaster.ca
                smnidorf@gmail.com
                alomranm@smh.ca
                nandini.gupta@medportal.ca
                teohh@smh.ca
                1-416-864-5559 , FriedrichJ@smh.ca
                Journal
                BMC Cardiovasc Disord
                BMC Cardiovasc Disord
                BMC Cardiovascular Disorders
                BioMed Central (London )
                1471-2261
                29 August 2015
                29 August 2015
                2015
                : 15
                : 96
                Affiliations
                [ ]Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON Canada
                [ ]Division of Vascular Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON Canada
                [ ]Division of Endocrinology & Metabolism, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON Canada
                [ ]Department of Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON Canada
                [ ]Department of Medicine, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON Canada
                [ ]Department of Critical Care, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON Canada
                [ ]Department of Surgery, University of Toronto, Toronto, ON Canada
                [ ]Department of Medicine and Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON Canada
                [ ]Department of Medicine, McMaster University, Hamilton, ON Canada
                [ ]Heart Research Institute, Perth, WA Australia
                Article
                68
                10.1186/s12872-015-0068-3
                4553011
                26318871
                2168d8a9-acbb-47bf-8c4e-674802385172
                © Verma et al. 2015

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 26 March 2015
                : 8 July 2015
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

                Cardiovascular Medicine
                colchicine,cardiovascular disease,meta-analysis
                Cardiovascular Medicine
                colchicine, cardiovascular disease, meta-analysis

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