Adverse events of colchicine for cardiovascular diseases: a comprehensive meta-analysis of 14 188 patients from 21 randomized controlled trials

Journal of Cardiovascular Medicine - Tập 22 Số 8 - Trang 637-644 - 2021
Alessandro Andreis1, Massimo Imazio, Stefano Avondo, Matteo Casula, Elena Paneva, Francesco Piroli, Gaetano Maria De Ferrari
1Department of Medical Sciences, University of Torino, University Cardiology, AOU Città della Salute e della Scienza di Torino, Turin, Italy.

Tóm tắt

Aims

Colchicine has an emerging role in the cardiovascular field, although, concerns for side effects, especially gastrointestinal, limit its prescription. We aimed at evaluating reported side effects of colchicine for cardiovascular indications.

Methods

We performed a meta-analysis of published randomized controlled trials on colchicine for the treatment of cardiovascular diseases. Random-effects meta-analysis was used to assess the risk of adverse events and drug withdrawal. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity.

Results

Among 14 188 patients, 7136 patients received colchicine while the other 7052 received placebo. The occurrence of any adverse event with colchicine was reported in 15.3 vs. 13.9% patients [relative risk (RR) 1.26, 95% confidence interval (CI) 0.96–1.64, P = 0.09]. Gastrointestinal events were reported in 16.1 vs. 12.2% (RR 2.16, 95% CI 1.50–3.12, P < 0.001), while diarrhea was reported in 12.5 vs. 8.1% (RR 2.77, 95% CI 1.55–4.94, P < 0.001). The risk of gastrointestinal events increased with daily dose and shorter treatment duration. Myalgias were observed in 21 vs. 18% patients (RR 1.16, 95% CI 1.02–1.32, P = 0.03). Other adverse events such as myotoxicity, hepatic adverse events, hematologic adverse events, cutaneous adverse events, infection or death were not increased by colchicine treatment. Colchicine discontinuation was reported in 4.8 vs. 3.4% patients (RR 1.54, 95% CI 1.20–1.99, P < 0.001).

Conclusion

Colchicine is associated with increased risk of gastrointestinal events and myalgias, but not of other adverse events. The risk of gastrointestinal events may be avoided with lower dose (0.5 mg/daily) and is inversely related to treatment duration, possibly due to early drug discontinuation or drug tolerance.

Từ khóa


Tài liệu tham khảo

Dasgeb, 2018, Colchicine: an ancient drug with novel applications, Br J Dermatol, 178, 350, 10.1111/bjd.15896

Chen, 2017, Teaching an old dog new tricks: colchicine in cardiovascular medicine, Am J Cardiovasc Drugs, 17, 347, 10.1007/s40256-017-0226-3

Imazio, 2016, Colchicine for cardiovascular medicine, Future Cardiol, 12, 9, 10.2217/fca.15.59

Andreis, 2020, Colchicine for the treatment of cardiovascular diseases: old drug, new targets, J Cardiovasc Med (Hagerstown)

Webb, 2020, Colchicine for secondary cardiovascular prevention: a systematic review, Pharmacotherapy, 40, 575, 10.1002/phar.2401

Andreis, 2019, Contemporary diagnosis and treatment of recurrent pericarditis, Expert Rev Cardiovasc Ther, 17, 817, 10.1080/14779072.2019.1691916

Liberati, 2009, The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration, PLoS Med, 6, e1000100, 10.1371/journal.pmed.1000100

Imazio, 2005, Colchicine as first-choice therapy for recurrent pericarditis: results of the CORE (COlchicine for REcurrent pericarditis) trial, Arch Intern Med, 165, 1987, 10.1001/archinte.165.17.1987

Imazio, 2005, Colchicine in addition to conventional therapy for acute pericarditis: results of the COlchicine for acute PEricarditis (COPE) trial, Circulation, 112, 2012, 10.1161/CIRCULATIONAHA.105.542738

Imazio, 2011, Colchicine reduces postoperative atrial fibrillation: results of the Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) atrial fibrillation substudy, Circulation, 124, 2290, 10.1161/CIRCULATIONAHA.111.026153

Imazio, 2011, Colchicine for recurrent pericarditis (CORP): a randomized trial, Ann Intern Med, 155, 409, 10.7326/0003-4819-155-7-201110040-00359

Imazio, 2013, A randomized trial of colchicine for acute pericarditis, N Engl J Med, 369, 1522, 10.1056/NEJMoa1208536

Imazio, 2014, Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation: the COPPS-2 randomized clinical trial, JAMA, 312, 1016, 10.1001/jama.2014.11026

Imazio, 2014, Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial, Lancet, 383, 2232, 10.1016/S0140-6736(13)62709-9

Liebenberg, 2016, A prospective investigation into the effect of colchicine on tuberculous pericarditis, Cardiovasc J Afr, 27, 350, 10.5830/CVJA-2016-035

Sambola, 2019, Colchicine administered in the first episode of acute idiopathic pericarditis: a randomized multicenter open-label study, Rev Esp Cardiol (Engl Ed), 72, 709, 10.1016/j.recesp.2018.11.021

Deftereos, 2013, Colchicine treatment for the prevention of bare-metal stent restenosis in diabetic patients, J Am Coll Cardiol, 61, 1679, 10.1016/j.jacc.2013.01.055

Spyridon, 2015, Anti-inflammatory treatment with colchicine in acute myocardial infarction, Circulation, 132, 1395, 10.1161/CIRCULATIONAHA.115.017611

Giannopoulos, 2015, Usefulness of colchicine to reduce perioperative myocardial damage in patients who underwent on-pump coronary artery bypass grafting, Am J Cardiol, 115, 1376, 10.1016/j.amjcard.2015.02.036

O’Keefe, 1992, Ineffectiveness of colchicine for the prevention of restenosis after coronary angioplasty, J Am Coll Cardiol, 19, 1597, 10.1016/0735-1097(92)90624-V

Tardif, 2019, Efficacy and safety of low-dose colchicine after myocardial infarction, N Engl J Med, 381, 2497, 10.1056/NEJMoa1912388

Raju, 2012, 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, 10.1007/s11239-011-0637-y

Shah, 2020, Effects of acute colchicine administration prior to percutaneous coronary intervention: COLCHICINE-PCI randomized trial, Circ Cardiovasc Interv, 13, e008717, 10.1161/CIRCINTERVENTIONS.119.008717

Nidorf, 2020, Colchicine in patients with chronic coronary disease, N Engl J Med, 383, 1838, 10.1056/NEJMoa2021372

Bessissow, 2018, Colchicine for Prevention of Perioperative Atrial Fibrillation in patients undergoing lung resection surgery: a pilot randomized controlled study, Eur J Cardiothorac Surg, 53, 945, 10.1093/ejcts/ezx422

Deftereos, 2012, Colchicine for prevention of early atrial fibrillation recurrence after pulmonary vein isolation: a randomized controlled study, J Am Coll Cardiol, 60, 1790, 10.1016/j.jacc.2012.07.031

Tabbalat, 2016, Effect of ColchiciNe on the InciDence of Atrial Fibrillation in open heart surgery patients: END-AF trial, Am Heart J, 178, 102, 10.1016/j.ahj.2016.05.006

Chappey, 1993, Colchicine disposition in human leukocytes after single and multiple oral administration, Clin Pharmacol Ther, 54, 360, 10.1038/clpt.1993.161

Dalbeth, 2014, Mechanism of action of colchicine in the treatment of gout, Clin Ther, 36, 1465, 10.1016/j.clinthera.2014.07.017

Horioka, 2020, Acute colchicine poisoning causes endotoxemia via the destruction of intestinal barrier function: the curative effect of endotoxin prevention in a murine model, Dig Dis Sci, 65, 132, 10.1007/s10620-019-05729-w

Ozen, 2017, Colchicine resistance and intolerance in Familial Mediterranean Fever: definition, causes, and alternative treatments, Semin Arthritis Rheum, 47, 115, 10.1016/j.semarthrit.2017.03.006

Kuncl, 1987, Colchicine myopathy and neuropathy, N Engl J Med, 316, 1562, 10.1056/NEJM198706183162502

Slobodnick, 2018, Update on colchicine, 2017, Rheumatology (Oxford), 57, i4, 10.1093/rheumatology/kex453

Medani, 2016, Colchicine toxicity in renal patients – are we paying attention?, Clin Nephrol, 86, 100, 10.5414/CN108343

Cerquaglia, 2005, Pharmacological and clinical basis of treatment of Familial Mediterranean Fever (FMF) with colchicine or analogues: an update, Curr Drug Targets Inflamm Allergy, 4, 117, 10.2174/1568010053622984

Zemer, 1986, Colchicine in the prevention and treatment of the amyloidosis of Familial Mediterranean Fever, N Engl J Med, 314, 1001, 10.1056/NEJM198604173141601

Srivastava, 2018, Does long term colchicine prevent degradation of collagen fiber network in osteoarthritis?, Int J Rheum Dis, 21, 114, 10.1111/1756-185X.13022