Downloaded from http://heart.bmj.com/ on February 6, 2016 - Published by group.bmj.com
Heart Online First, published on February 2, 2016 as 10.1136/heartjnl-2015-309167 Editorial
Is colchicine a promising novel treatment option for cardiovascular medicine? Massimo Imazio,1,2 Fiorenzo Gaita3 Colchicine is a very old drug of vegetal origin: its first use has been described for rheumatic complaints and mentioned in an old Egyptian medical papyrus, the Ebers Papyrus, dating back to 1550 BC. Colchicine has been especially prescribed for the treatment of gouty attacks: the first description of this use has been reported in De Materia Medica (latin for ‘On Medical Material’), an encyclopaedia and pharmacopoeia of herbs and the medicines that can be obtained from them, written by Pedanius Dioscorides between 50 AD and 70 AD. The plants were introduced into North America by Benjamin Franklin, who used them to treat his gout. In 1820, colchicine was isolated by the French chemists PS Pelletier and JB Caventou. In 1833, PL Geiger purified the active substance and gave it the name of colchicine. However, the active compound, a tricyclic alkaloid, was first reported in 1955 and its name was derived from Colchis, an ancient region close to the Black Sea, where plants of Colchicum were widespread (figure 1).1 2 In 2009, the US Food and Drug Administration (FDA) approved the use of colchicine for familial Mediterranean fever (FMF), and the prevention and treatment of gouty attacks. The first use of colchicine in cardiovascular medicine was the treatment and prevention of recurrent pericarditis. Following its efficacy in the treatment and prevention of poliserositis attacks in FMF, Bayes de Luna et al reported the successful use of the drug in three cases in The Lancet.3 The primary mechanism of action of colchicine is tubulin disruption and thus the inhibition of microtubule polymerisation, an essential component of cellular cytoskeleton.4 5 This leads to subsequent
downregulation of multiple inflammatory pathways and modulation of innate immunity. The drug is able to concentrate especially in granulocytes and exert a significant anti-inflammatory effect even when used at low oral doses such as 0.5 mg/day.1 2 6 This unique anti-inflammatory mechanism of action of the drug has attracted additional research in cardiovascular medicine, especially in the field of atherosclerosis in order to reduce plaque inflammation and rupture with the aim of preventing an acute cardiovascular event,7 8 restenosis after coronary angioplasty,9 atrial fibrillation (AF) after cardiac surgery10 and AF ablation (figure 2).11 12 In the Heart meta-analysis by Hemkens et al,13 38 trials were included with a total number of 4951 patients in order to assess the potential efficacy of colchicine on outcomes such as all-cause mortality, myocardial infarction, cardiovascular mortality as well as its safety. Trials on the use of colchicine to treat pericarditis or arrhythmias were not included. Most included trials were small with a median
number of 84 patients and this is a limitation especially of the current available research. Nevertheless, four RCTs included 1230 patients comparing colchicine with placebo or usual care in specific cardiovascular settings (after elective angioplasty, patients with diabetes undergoing bare-metal stent implantation, stable chronic heart failure and stable coronary disease).8 9 14 15 The quality of evidence was moderate in most cases due to imprecision and low for the assessment of adverse events. Colchicine had no effect on all-cause-mortality (RR 0.94, 95% CI 0.81 to 1.09; I2=29%; 29 trials) and reduced cardiovascular mortality in some but not all meta-analytical models (random-effects RR 0.34, 95% CI 0.09 to 1.21, I2=0%; Peto’s OR 0.24, 95% CI 0.09 to 0.64, I2=0%; Mantel-Haenszel fixed-effect RR 0.20, 95% CI 0.06 to 0.68, I2=0%; 6 trials). On the contrary, colchicine reduced the risk of myocardial infarction (RR 0.20, 95% CI 0.07 to 0.57; 2 trials). Overall, colchicine did not increase total adverse events (RR 1.52, 95% CI 0.93 to 2.46, I2=45%; 11 trials) but increased the risk of gastrointestinal intolerance (RR 1.83, 95% CI 1.03 to 3.26, I2=74%; 11 trials), that is the most common and well known side effect of the drug. Reporting of serious adverse events was inconsistent and no severe adverse event occurred over 824 patientyears (four trials). Moreover the effects in high cardiovascular risk populations were similar (four trials; 1230 patients). In the
1
Cardiology Department, Maria Vittoria Hospital, Torino, Italy; 2Department of Public Health and Pediatrics, University of Torino, Torino, Italy; 3University Division of Cardiology, Department of Medical Sciences, Città della Salute e della Scienza, University of Torino, Torino, Italy Correspondence to Professor Massimo Imazio, Cardiology Department, Maria Vittoria Hospital Torino, Italy; [email protected], massimo.imazio@ unito.it
Figure 1 Colchicine is a tricyclic alkaloid derived from colchicum plants. The name is derived from Colchis, an ancient region and kingdom close to the Black Sea, where plants were widespread. Imazio M, Gaita F. Heart Month 2016 Vol 0 No 0
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Copyright Article author (or their employer) 2016. Produced by BMJ Publishing Group Ltd (& BCS) under licence.
Downloaded from http://heart.bmj.com/ on February 6, 2016 - Published by group.bmj.com
Editorial
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Figure 2 The primary mechanism of action of colchicine is tubulin disruption and thus the inhibition of microtubule polymerisation, an essential component of cellular cytoskeleton. This leads to subsequent potential anti-inflammatory effects especially mediated by its capability to concentrate and act on granulocytes. Such effects in cardiovascular medicine may have application in pericarditis, pericarditis-related atrial fibrillation and atherosclerotic vascular disease. majority of the analysed trials (68%), colchicine was administered at doses ≤1 mg/ day, and the authors found no evidence to support colchicine doses >1 mg/day. The present meta-analysis (13) is an important step towards an increased awareness of the potentiality of colchicine for cardiovascular medicine. There are three main key points: (1) there is consistent and growing evidence suggesting that colchicine may exert cardiovascular effects that may be beneficial to patients, (2) the drug is cheap and rather safe when used at low doses (1 mg/day in cardiovascular medicine. In conclusion, colchicine seems a promising novel treatment option for different cardiovascular applications (eg, especially acute and chronic ischaemic heart diseases, prevention of AF in specific conditions such as after cardiac surgery and after AF ablation procedures) beyond the well established efficacy in acute and recurrent pericarditis.16–20 Ongoing trials will soon provide additional evidence for or against a possible indication in acute and chronic ischaemic heart diseases,21–23 but we need additional basic and clinical research to better understand the molecular mechanisms, and to verify the real efficacy of colchicine. Nowadays, colchicine remains an ancient drug, but could become a new standard of care, especially for ischaemic heart disease, with a potentiality very similar to that currently recognised for aspirin or statins in this setting.
2
Contributors All the authors contributed to the conception of the work, the acquisition, the analysis and interpretation of data, as well as drafting the work or revising it critically for important intellectual content. All authors provided final approval of the submitted paper. Competing interests None declared. Provenance and peer review Commissioned; internally peer reviewed. To cite Imazio M, Gaita F. Heart Published Online First: [ please include Day Month Year] doi:10.1136/ heartjnl-2015-309167
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▸ http://dx.doi.org/10.1136/heartjnl-2015-308542 Heart 2016;0:1–2. doi:10.1136/heartjnl-2015-309167
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REFERENCES
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Imazio M. Colchicine for pericarditis. Trends Cardiovasc Med 2015;25:129–36. Imazio M, Gaita F. Colchicine for cardiovascular medicine. Future Cardiol 2016;12:9–16. Rodríguez de la Serna A, Guindo Soldevila J, Martí Claramunt V, et al. Colchicine for recurrent pericarditis. Lancet 1987;2:1517. Dalbeth N, Lauterio TJ, Wolfe HR. Mechanism of action of colchicine in the treatment of gout. Clin Ther 2014;36:1465–79. Leung YY, Yao Hui LL, Kraus VB. Colchicine-Update on mechanisms of action and therapeutic uses. Semin Arthritis Rheum 2015;45:341–50. Imazio M, Brucato A, Trinchero R, et al. Colchicine for pericarditis: hype or hope? Eur Heart J 2009;30:532–9. Deftereos S, Giannopoulos G, Papoutsidakis N, et al. Colchicine and the heart: pushing the envelope. J Am Coll Cardiol 2013;62:1817–25. Nidorf SM, Eikelboom JW, Budgeon CA, et al. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol 2013;61:404–10. O’Keefe JH Jr, McCallister BD, Bateman TM, et al. Ineffectiveness of colchicine for the prevention of
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restenosis after coronary angioplasty. J Am Coll Cardiol 1992;19:1597–600. Imazio M, Brucato A, Ferrazzi P, et al. COPPS Investigators. Colchicine reduces postoperative atrial fibrillation: results of the Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) atrial fibrillation substudy. Circulation 2011;124:2290–5. Imazio M, Brucato A, Ferrazzi P, et al. COPPS-2 Investigators. Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation: the COPPS-2 randomized clinical trial. JAMA 2014;312:1016–23. Deftereos S, Giannopoulos G, Kossyvakis C, et al. Colchicine for prevention of early atrial fibrillation recurrence after pulmonary vein isolation: a randomized controlled study. J Am Coll Cardiol 2012;60:1790–6. Hemkens LG, Hannah Ewald H, Gloy VL, et al. Cardiovascular effects and safety of long-term colchicine treatment: cochrane review & meta-analysis. Heart 2016; in press. Deftereos S, Giannopoulos G, Raisakis K, et al. Colchicine treatment for the prevention of bare-metal stent restenosis in diabetic patients. J Am Coll Cardiol 2013;61:1679–85. Deftereos S, Giannopoulos G, Panagopoulou V, et al. Anti-inflammatory treatment with colchicine in stable chronic heart failure: a prospective, randomized study. JACC Heart Failure 2014;2:131–7. Imazio M, Brucato A, Forno D, et al. Efficacy and safety of colchicine for pericarditis prevention. Systematic review and meta-analysis. Heart 2012;98:1078–82. Imazio M, Brucato A, Cemin R, et al. ICAP Investigators. A randomized trial of colchicine for acute pericarditis. N Engl J Med 2013;369:1522–8. 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;383:2232–7. Imazio M, Brucato A, Belli R, et al. Colchicine for the prevention of pericarditis: what we know and what we do not know in 2014—systematic review and meta-analysis. J Cardiovasc Med (Hagerstown) 2014;15:840–6. Imazio M, Gaita F, LeWinter M. Evaluation and treatment of pericarditis: a systematic review. JAMA 2015;314:1498–506. COLPET Protocol. A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effects of Colchicine on Vascular Inflammation as Assessed With Position Emission Tomography (PET) Imaging in Patients With Atherosclerotic Vascular Disease (COLPET). Secondary A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effects of Colchicine on Vascular Inflammation as Assessed With Position Emission Tomography (PET) Imaging in Patients With Atherosclerotic Vascular Disease (COLPET) NCT02162303. https://clinicaltrials.gov/ct2/ show/NCT02162303 COACS Protocol. Colchicine for Acute Coronary Syndromes. A Multicenter Double Blind Randomized Trial. Secondary Colchicine for Acute Coronary Syndromes. A Multicenter Double Blind Randomized Trial NCT01906749. https://clinicaltrials.gov/ct2/ show/NCT01906749 LoDoCo2 Protocol. “The LoDoCo2 Trial": Low Dose Colchicine for secondary prevention of cardiovascular disease. Secondary “The LoDoCo2 Trial”: Low Dose Colchicine for secondary prevention of cardiovascular disease ACTRN12614000093684. https://www. anzctr.org.au/Trial/Registration/TrialReview.aspx? ACTRN=12614000093684
Imazio M, Gaita F. Heart Month 2016 Vol 0 No 0
Downloaded from http://heart.bmj.com/ on February 6, 2016 - Published by group.bmj.com
Is colchicine a promising novel treatment option for cardiovascular medicine? Massimo Imazio and Fiorenzo Gaita Heart published online February 2, 2016
Updated information and services can be found at: http://heart.bmj.com/content/early/2016/02/02/heartjnl-2015-309167
These include:
References Email alerting service
Topic Collections
This article cites 19 articles, 3 of which you can access for free at: http://heart.bmj.com/content/early/2016/02/02/heartjnl-2015-309167 #BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Articles on similar topics can be found in the following collections Drugs: cardiovascular system (8547) Interventional cardiology (2854) Epidemiology (3584) Clinical diagnostic tests (4669) Acute coronary syndromes (2655) Metabolic disorders (1000)
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
Heart Online First, published on February 2, 2016 as 10.1136/heartjnl-2015-309167 Editorial
Is colchicine a promising novel treatment option for cardiovascular medicine? Massimo Imazio,1,2 Fiorenzo Gaita3 Colchicine is a very old drug of vegetal origin: its first use has been described for rheumatic complaints and mentioned in an old Egyptian medical papyrus, the Ebers Papyrus, dating back to 1550 BC. Colchicine has been especially prescribed for the treatment of gouty attacks: the first description of this use has been reported in De Materia Medica (latin for ‘On Medical Material’), an encyclopaedia and pharmacopoeia of herbs and the medicines that can be obtained from them, written by Pedanius Dioscorides between 50 AD and 70 AD. The plants were introduced into North America by Benjamin Franklin, who used them to treat his gout. In 1820, colchicine was isolated by the French chemists PS Pelletier and JB Caventou. In 1833, PL Geiger purified the active substance and gave it the name of colchicine. However, the active compound, a tricyclic alkaloid, was first reported in 1955 and its name was derived from Colchis, an ancient region close to the Black Sea, where plants of Colchicum were widespread (figure 1).1 2 In 2009, the US Food and Drug Administration (FDA) approved the use of colchicine for familial Mediterranean fever (FMF), and the prevention and treatment of gouty attacks. The first use of colchicine in cardiovascular medicine was the treatment and prevention of recurrent pericarditis. Following its efficacy in the treatment and prevention of poliserositis attacks in FMF, Bayes de Luna et al reported the successful use of the drug in three cases in The Lancet.3 The primary mechanism of action of colchicine is tubulin disruption and thus the inhibition of microtubule polymerisation, an essential component of cellular cytoskeleton.4 5 This leads to subsequent
downregulation of multiple inflammatory pathways and modulation of innate immunity. The drug is able to concentrate especially in granulocytes and exert a significant anti-inflammatory effect even when used at low oral doses such as 0.5 mg/day.1 2 6 This unique anti-inflammatory mechanism of action of the drug has attracted additional research in cardiovascular medicine, especially in the field of atherosclerosis in order to reduce plaque inflammation and rupture with the aim of preventing an acute cardiovascular event,7 8 restenosis after coronary angioplasty,9 atrial fibrillation (AF) after cardiac surgery10 and AF ablation (figure 2).11 12 In the Heart meta-analysis by Hemkens et al,13 38 trials were included with a total number of 4951 patients in order to assess the potential efficacy of colchicine on outcomes such as all-cause mortality, myocardial infarction, cardiovascular mortality as well as its safety. Trials on the use of colchicine to treat pericarditis or arrhythmias were not included. Most included trials were small with a median
number of 84 patients and this is a limitation especially of the current available research. Nevertheless, four RCTs included 1230 patients comparing colchicine with placebo or usual care in specific cardiovascular settings (after elective angioplasty, patients with diabetes undergoing bare-metal stent implantation, stable chronic heart failure and stable coronary disease).8 9 14 15 The quality of evidence was moderate in most cases due to imprecision and low for the assessment of adverse events. Colchicine had no effect on all-cause-mortality (RR 0.94, 95% CI 0.81 to 1.09; I2=29%; 29 trials) and reduced cardiovascular mortality in some but not all meta-analytical models (random-effects RR 0.34, 95% CI 0.09 to 1.21, I2=0%; Peto’s OR 0.24, 95% CI 0.09 to 0.64, I2=0%; Mantel-Haenszel fixed-effect RR 0.20, 95% CI 0.06 to 0.68, I2=0%; 6 trials). On the contrary, colchicine reduced the risk of myocardial infarction (RR 0.20, 95% CI 0.07 to 0.57; 2 trials). Overall, colchicine did not increase total adverse events (RR 1.52, 95% CI 0.93 to 2.46, I2=45%; 11 trials) but increased the risk of gastrointestinal intolerance (RR 1.83, 95% CI 1.03 to 3.26, I2=74%; 11 trials), that is the most common and well known side effect of the drug. Reporting of serious adverse events was inconsistent and no severe adverse event occurred over 824 patientyears (four trials). Moreover the effects in high cardiovascular risk populations were similar (four trials; 1230 patients). In the
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Cardiology Department, Maria Vittoria Hospital, Torino, Italy; 2Department of Public Health and Pediatrics, University of Torino, Torino, Italy; 3University Division of Cardiology, Department of Medical Sciences, Città della Salute e della Scienza, University of Torino, Torino, Italy Correspondence to Professor Massimo Imazio, Cardiology Department, Maria Vittoria Hospital Torino, Italy; [email protected], massimo.imazio@ unito.it
Figure 1 Colchicine is a tricyclic alkaloid derived from colchicum plants. The name is derived from Colchis, an ancient region and kingdom close to the Black Sea, where plants were widespread. Imazio M, Gaita F. Heart Month 2016 Vol 0 No 0
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Copyright Article author (or their employer) 2016. Produced by BMJ Publishing Group Ltd (& BCS) under licence.
Downloaded from http://heart.bmj.com/ on February 6, 2016 - Published by group.bmj.com
Editorial
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Figure 2 The primary mechanism of action of colchicine is tubulin disruption and thus the inhibition of microtubule polymerisation, an essential component of cellular cytoskeleton. This leads to subsequent potential anti-inflammatory effects especially mediated by its capability to concentrate and act on granulocytes. Such effects in cardiovascular medicine may have application in pericarditis, pericarditis-related atrial fibrillation and atherosclerotic vascular disease. majority of the analysed trials (68%), colchicine was administered at doses ≤1 mg/ day, and the authors found no evidence to support colchicine doses >1 mg/day. The present meta-analysis (13) is an important step towards an increased awareness of the potentiality of colchicine for cardiovascular medicine. There are three main key points: (1) there is consistent and growing evidence suggesting that colchicine may exert cardiovascular effects that may be beneficial to patients, (2) the drug is cheap and rather safe when used at low doses (1 mg/day in cardiovascular medicine. In conclusion, colchicine seems a promising novel treatment option for different cardiovascular applications (eg, especially acute and chronic ischaemic heart diseases, prevention of AF in specific conditions such as after cardiac surgery and after AF ablation procedures) beyond the well established efficacy in acute and recurrent pericarditis.16–20 Ongoing trials will soon provide additional evidence for or against a possible indication in acute and chronic ischaemic heart diseases,21–23 but we need additional basic and clinical research to better understand the molecular mechanisms, and to verify the real efficacy of colchicine. Nowadays, colchicine remains an ancient drug, but could become a new standard of care, especially for ischaemic heart disease, with a potentiality very similar to that currently recognised for aspirin or statins in this setting.
2
Contributors All the authors contributed to the conception of the work, the acquisition, the analysis and interpretation of data, as well as drafting the work or revising it critically for important intellectual content. All authors provided final approval of the submitted paper. Competing interests None declared. Provenance and peer review Commissioned; internally peer reviewed. To cite Imazio M, Gaita F. Heart Published Online First: [ please include Day Month Year] doi:10.1136/ heartjnl-2015-309167
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▸ http://dx.doi.org/10.1136/heartjnl-2015-308542 Heart 2016;0:1–2. doi:10.1136/heartjnl-2015-309167
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REFERENCES
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Imazio M. Colchicine for pericarditis. Trends Cardiovasc Med 2015;25:129–36. Imazio M, Gaita F. Colchicine for cardiovascular medicine. Future Cardiol 2016;12:9–16. Rodríguez de la Serna A, Guindo Soldevila J, Martí Claramunt V, et al. Colchicine for recurrent pericarditis. Lancet 1987;2:1517. Dalbeth N, Lauterio TJ, Wolfe HR. Mechanism of action of colchicine in the treatment of gout. Clin Ther 2014;36:1465–79. Leung YY, Yao Hui LL, Kraus VB. Colchicine-Update on mechanisms of action and therapeutic uses. Semin Arthritis Rheum 2015;45:341–50. Imazio M, Brucato A, Trinchero R, et al. Colchicine for pericarditis: hype or hope? Eur Heart J 2009;30:532–9. Deftereos S, Giannopoulos G, Papoutsidakis N, et al. Colchicine and the heart: pushing the envelope. J Am Coll Cardiol 2013;62:1817–25. Nidorf SM, Eikelboom JW, Budgeon CA, et al. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol 2013;61:404–10. O’Keefe JH Jr, McCallister BD, Bateman TM, et al. Ineffectiveness of colchicine for the prevention of
22
23
restenosis after coronary angioplasty. J Am Coll Cardiol 1992;19:1597–600. Imazio M, Brucato A, Ferrazzi P, et al. COPPS Investigators. Colchicine reduces postoperative atrial fibrillation: results of the Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) atrial fibrillation substudy. Circulation 2011;124:2290–5. Imazio M, Brucato A, Ferrazzi P, et al. COPPS-2 Investigators. Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation: the COPPS-2 randomized clinical trial. JAMA 2014;312:1016–23. Deftereos S, Giannopoulos G, Kossyvakis C, et al. Colchicine for prevention of early atrial fibrillation recurrence after pulmonary vein isolation: a randomized controlled study. J Am Coll Cardiol 2012;60:1790–6. Hemkens LG, Hannah Ewald H, Gloy VL, et al. Cardiovascular effects and safety of long-term colchicine treatment: cochrane review & meta-analysis. Heart 2016; in press. Deftereos S, Giannopoulos G, Raisakis K, et al. Colchicine treatment for the prevention of bare-metal stent restenosis in diabetic patients. J Am Coll Cardiol 2013;61:1679–85. Deftereos S, Giannopoulos G, Panagopoulou V, et al. Anti-inflammatory treatment with colchicine in stable chronic heart failure: a prospective, randomized study. JACC Heart Failure 2014;2:131–7. Imazio M, Brucato A, Forno D, et al. Efficacy and safety of colchicine for pericarditis prevention. Systematic review and meta-analysis. Heart 2012;98:1078–82. Imazio M, Brucato A, Cemin R, et al. ICAP Investigators. A randomized trial of colchicine for acute pericarditis. N Engl J Med 2013;369:1522–8. 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;383:2232–7. Imazio M, Brucato A, Belli R, et al. Colchicine for the prevention of pericarditis: what we know and what we do not know in 2014—systematic review and meta-analysis. J Cardiovasc Med (Hagerstown) 2014;15:840–6. Imazio M, Gaita F, LeWinter M. Evaluation and treatment of pericarditis: a systematic review. JAMA 2015;314:1498–506. COLPET Protocol. A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effects of Colchicine on Vascular Inflammation as Assessed With Position Emission Tomography (PET) Imaging in Patients With Atherosclerotic Vascular Disease (COLPET). Secondary A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effects of Colchicine on Vascular Inflammation as Assessed With Position Emission Tomography (PET) Imaging in Patients With Atherosclerotic Vascular Disease (COLPET) NCT02162303. https://clinicaltrials.gov/ct2/ show/NCT02162303 COACS Protocol. Colchicine for Acute Coronary Syndromes. A Multicenter Double Blind Randomized Trial. Secondary Colchicine for Acute Coronary Syndromes. A Multicenter Double Blind Randomized Trial NCT01906749. https://clinicaltrials.gov/ct2/ show/NCT01906749 LoDoCo2 Protocol. “The LoDoCo2 Trial": Low Dose Colchicine for secondary prevention of cardiovascular disease. Secondary “The LoDoCo2 Trial”: Low Dose Colchicine for secondary prevention of cardiovascular disease ACTRN12614000093684. https://www. anzctr.org.au/Trial/Registration/TrialReview.aspx? ACTRN=12614000093684
Imazio M, Gaita F. Heart Month 2016 Vol 0 No 0
Downloaded from http://heart.bmj.com/ on February 6, 2016 - Published by group.bmj.com
Is colchicine a promising novel treatment option for cardiovascular medicine? Massimo Imazio and Fiorenzo Gaita Heart published online February 2, 2016
Updated information and services can be found at: http://heart.bmj.com/content/early/2016/02/02/heartjnl-2015-309167
These include:
References Email alerting service
Topic Collections
This article cites 19 articles, 3 of which you can access for free at: http://heart.bmj.com/content/early/2016/02/02/heartjnl-2015-309167 #BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Articles on similar topics can be found in the following collections Drugs: cardiovascular system (8547) Interventional cardiology (2854) Epidemiology (3584) Clinical diagnostic tests (4669) Acute coronary syndromes (2655) Metabolic disorders (1000)
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
