Role of Colchicine in Cardiovascular Disorders.

Inflammation has played a pivotal role in atherosclerosis and other cardiovascular disorders, prompting the exploration of anti-inflammatory therapies to improve cardiovascular outcomes. Colchicine, a well-established agent in conditions such as gout and familial Mediterranean fever, has emerged as a promising novel anti-inflammatory agent in the realm of cardiovascular diseases. Its ability to target both traditional risk factors and residual inflammatory risk marks a significant advancement in cardiovascular prevention strategies, indicating a new era in cardiovascular care. Landmark trials have supported the efficacy and safety of low-dose colchicine in reducing major adverse cardiovascular events when combined with standard therapies. In addition, its endorsement by major cardiovascular societies underscores its significance as the first targeted anti-inflammatory therapy for cardiovascular disease. However, careful monitoring for drug interactions and adverse effects, particularly on kidney and liver function, is essential for safe use. In this review, we aim to comprehensively summarize the mechanisms of action of colchicine, its molecular and biochemical targets in various cardiovascular conditions, and its pharmacokinetics, and delve deeply into the existing evidence on its safety and efficacy in the treatment of cardiovascular disorders, including coronary artery disease, pericarditis, atrial fibrillation, and heart failure.

[1]  M. Mamas,et al.  Efficacy and Safety of Colchicine for the Prevention of Postoperative Atrial Fibrillation Among Patients Undergoing Major Cardiothoracic Surgery: A Meta-analysis and Meta-regression of Randomized Controlled Trials , 2023, Journal of cardiovascular pharmacology.

[2]  A. Benz,et al.  Colchicine to Prevent Atrial Fibrillation Recurrence After Catheter Ablation: A Randomized, Placebo-Controlled Trial , 2023, Circulation. Arrhythmia and electrophysiology.

[3]  D. Angiolillo,et al.  P2Y12 Inhibitor Monotherapy Combined With Colchicine Following PCI in ACS Patients: The MACT Pilot Study. , 2023, JACC. Cardiovascular interventions.

[4]  R. de Caterina,et al.  NLRP3 inflammasome and interleukin-1 contributions to COVID-19-associated coagulopathy and immunothrombosis. , 2023, Cardiovascular research.

[5]  Zhenguo Liu,et al.  Colchicine usage for prevention of post atrial fibrillation ablation pericarditis in patients undergoing high‐power short‐duration ablation , 2023, Journal of cardiovascular electrophysiology.

[6]  Deepak L. Bhatt,et al.  Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials , 2023, The Lancet.

[7]  Jinqiang Zhuang,et al.  Colchicine for prevention of post-operative atrial fibrillation: Meta-analysis of randomized controlled trials , 2022, Frontiers in Cardiovascular Medicine.

[8]  H. Schunkert,et al.  Colchicine Impacts Leukocyte Trafficking in Atherosclerosis and Reduces Vascular Inflammation , 2022, Frontiers in Immunology.

[9]  K. Bilchick,et al.  Association of colchicine use for acute gout with clinical outcomes in acute decompensated heart failure , 2022, Clinical cardiology.

[10]  W. Masson,et al.  The Effect of Colchicine on Mortality, Mechanical Ventilation, and Length of Stay in Patients With COVID-19 Infection: An Updated Systematic Review and Meta-analysis of Randomized Clinical Trials. , 2022, American journal of therapeutics.

[11]  F. Dentali,et al.  Colchicine for COVID-19: targeting NLRP3 inflammasome to blunt hyperinflammation , 2022, Inflammation Research.

[12]  J. Tardif,et al.  Colchicine in Cardiovascular Disease: In-Depth Review , 2022, Circulation.

[13]  P. Izadpanah,et al.  Effects of colchicine on major adverse cardiac events in next 6-month period after acute coronary syndrome occurrence; a randomized placebo-control trial , 2021, BMC Cardiovascular Disorders.

[14]  Xuan Sun,et al.  CD47‐ and Integrin α4/β1‐Comodified‐Macrophage‐Membrane‐Coated Nanoparticles Enable Delivery of Colchicine to Atherosclerotic Plaque , 2021, Advanced healthcare materials.

[15]  J. Layland,et al.  COlchicine to Prevent PeriprocEdural myocardial Injury in Percutaneous Coronary Intervention (COPE-PCI): A descriptive cytokine pilot sub-study. , 2021, Cardiovascular revascularization medicine : including molecular interventions.

[16]  D. Maucort-Boulch,et al.  Effect of Colchicine on Myocardial Injury in Acute Myocardial Infarction , 2021, Circulation.

[17]  J. Lieberman,et al.  Inflammasome activation at the crux of severe COVID-19 , 2021, Nature Reviews Immunology.

[18]  F. Pinto,et al.  Low-Dose Colchicine in Coronary Artery Disease ― Systematic Review and Meta-Analysis ― , 2021, Circulation reports.

[19]  M. Traini,et al.  Colchicine inhibits ROS generation in response to glycoprotein VI stimulation , 2021, Scientific Reports.

[20]  D. Gaudet,et al.  Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial , 2021, The Lancet Respiratory Medicine.

[21]  M. Landray,et al.  Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial , 2021, The Lancet Respiratory Medicine.

[22]  M. Imazio,et al.  Colchicine and the heart , 2021, European heart journal.

[23]  J. Layland,et al.  Colchicine to Prevent Periprocedural Myocardial Injury in Percutaneous Coronary Intervention , 2021, Circulation. Cardiovascular interventions.

[24]  A. Abbate,et al.  The Role of NLRP3 Inflammasome in Pericarditis , 2021, JACC. Basic to translational science.

[25]  M. Casula,et al.  Adverse events of colchicine for cardiovascular diseases: a comprehensive meta-analysis of 14 188 patients from 21 randomized controlled trials , 2021, Journal of cardiovascular medicine.

[26]  E. Pandzic,et al.  Colchicine Inhibits Neutrophil Extracellular Trap Formation in Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention , 2020, Journal of the American Heart Association.

[27]  G. Cimmino,et al.  Colchicine inhibits the prothrombotic effects of oxLDL in human endothelial cells. , 2020, Vascular pharmacology.

[28]  A. Abbate,et al.  Inflammasome formation in the lungs of patients with fatal COVID-19 , 2020, Inflammation research : official journal of the European Histamine Research Society ... [et al.].

[29]  J. Cornel,et al.  Short-term effect of low-dose colchicine on inflammatory biomarkers, lipids, blood count and renal function in chronic coronary artery disease and elevated high-sensitivity C-reactive protein , 2020, PloS one.

[30]  G. Hankey,et al.  Colchicine in Patients with Chronic Coronary Disease. , 2020, The New England journal of medicine.

[31]  R. Diaz,et al.  Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT) , 2020, European heart journal.

[32]  R. Whitbourn,et al.  Colchicine in Patients with Acute Coronary Syndrome: The Australian COPS Randomized Clinical Trial. , 2020, Circulation.

[33]  Y. Khader,et al.  Effect of Low-dose ColchiciNe on the InciDence of Atrial Fibrillation in Open Heart Surgery Patients: END-AF Low Dose Trial , 2020, The Journal of international medical research.

[34]  G. Dangas,et al.  Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019 , 2020, JAMA network open.

[35]  Binita Shah,et al.  Effects of Acute Colchicine Administration Prior to Percutaneous Coronary Intervention , 2020, Circulation. Cardiovascular interventions.

[36]  P. Ridker From CANTOS to CIRT to COLCOT to Clinic: Will All Atherosclerosis Patients Soon Be Treated With Combination Lipid-Lowering and Inflammation-Inhibiting Agents? , 2020, Circulation.

[37]  J. Grizzard,et al.  Management of Acute and Recurrent Pericarditis: JACC State-of-the-Art Review. , 2020, Journal of the American College of Cardiology.

[38]  R. Diaz,et al.  Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. , 2019, The New England journal of medicine.

[39]  A. Sambola,et al.  Colchicina administrada en el primer episodio de pericarditis aguda idiopática: estudio multicéntrico abierto y aleatorizado , 2019, Revista Española de Cardiología.

[40]  G. Hillis,et al.  The Low Dose Colchicine after Myocardial Infarction (LoDoCo-MI) study: A pilot randomized placebo controlled trial of colchicine following acute myocardial infarction. , 2019, American heart journal.

[41]  L. Chen,et al.  2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. , 2019, Circulation.

[42]  G. Hatemi,et al.  Update on the treatment of Behçet’s syndrome , 2019, Internal and Emergency Medicine.

[43]  P. Mody,et al.  Trends in acute pericarditis hospitalizations and outcomes among the elderly in the USA, 1999–2012 , 2018, European heart journal. Quality of care & clinical outcomes.

[44]  E. Füchtbauer,et al.  Diverse cellular architecture of atherosclerotic plaque derives from clonal expansion of a few medial SMCs. , 2017, JCI insight.

[45]  P. Libby,et al.  Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease , 2017, The New England journal of medicine.

[46]  J. C. Jorge,et al.  Colchicine to Reduce Atrial Fibrillation in the Postoperative Period of Myocardial Revascularization , 2016, Arquivos brasileiros de cardiologia.

[47]  N. Al-Attar,et al.  2015 ESC Guidelines for the diagnosis and management of pericardial diseases , 2015, European heart journal.

[48]  G. Filippatos,et al.  Anti‐Inflammatory Treatment With Colchicine in Acute Myocardial Infarction: A Pilot Study , 2015, Circulation.

[49]  M. Pillinger,et al.  Colchicine: old and new. , 2015, The American journal of medicine.

[50]  Y. Adler,et al.  Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation: the COPPS-2 randomized clinical trial. , 2014, JAMA.

[51]  Y. Adler,et al.  Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial , 2014, The Lancet.

[52]  Mandegar Mohammad Hossein,et al.  LOW DOSE COLCHICINE IN PREVENTION OF ATRIAL FIBRILLATION AFTER CORONARY ARTERY BYPASS GRAFT: A DOUBLE BLIND CLINICAL TRIAL , 2014 .

[53]  Ira Tabas,et al.  Inflammation and its Resolution as Determinants of Acute Coronary Syndromes , 2014, Circulation research.

[54]  M. Cleman,et al.  Anti-inflammatory treatment with colchicine in stable chronic heart failure: a prospective, randomized study. , 2014, JACC. Heart failure.

[55]  M. Cleman,et al.  Colchicine for prevention of atrial fibrillation recurrence after pulmonary vein isolation: mid-term efficacy and effect on quality of life. , 2014, Heart rhythm.

[56]  Y. Adler,et al.  A randomized trial of colchicine for acute pericarditis. , 2013, The New England journal of medicine.

[57]  Hong Zhang,et al.  Microtubule Dynamics Control Tail Retraction in Migrating Vascular Endothelial Cells , 2013, Molecular Cancer Therapeutics.

[58]  M. Cleman,et al.  Colchicine treatment for the prevention of bare-metal stent restenosis in diabetic patients. , 2013, Journal of the American College of Cardiology.

[59]  B. Pamuk,et al.  Evaluation of circulating endothelial biomarkers in familial Mediterranean fever , 2013, Rheumatology International.

[60]  J. Eikelboom,et al.  Low-dose colchicine for secondary prevention of cardiovascular disease. , 2013, Journal of the American College of Cardiology.

[61]  C. Stefanadis,et al.  Colchicine for prevention of early atrial fibrillation recurrence after pulmonary vein isolation: a randomized controlled study. , 2012, Journal of the American College of Cardiology.

[62]  Y. Adler,et al.  Colchicine Reduces Postoperative Atrial Fibrillation: Results of the Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) Atrial Fibrillation Substudy , 2011, Circulation.

[63]  Y. Adler,et al.  Colchicine for Recurrent Pericarditis (CORP) , 2011, Annals of Internal Medicine.

[64]  Y. Adler,et al.  COlchicine for the Prevention of the Post-pericardiotomy Syndrome (COPPS): a multicentre, randomized, double-blind, placebo-controlled trial. , 2010, European heart journal.

[65]  J. Woods,et al.  Cholesterol in human atherosclerotic plaque is a marker for underlying disease state and plaque vulnerability , 2010, Lipids in Health and Disease.

[66]  R. Terkeltaub,et al.  High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. , 2010, Arthritis and rheumatism.

[67]  K. Aziz,et al.  Effect of cholesterol crystals on plaques and intima in arteries of patients with acute coronary and cerebrovascular syndromes. , 2009, The American journal of cardiology.

[68]  P. Thompson,et al.  Effect of colchicine (0.5 mg twice daily) on high-sensitivity C-reactive protein independent of aspirin and atorvastatin in patients with stable coronary artery disease. , 2007, The American journal of cardiology.

[69]  A. Topeli,et al.  Rhabdomyolysis in a Patient Treated with Colchicine and Atorvastatin , 2006, The Annals of pharmacotherapy.

[70]  F. Martinon,et al.  Gout-associated uric acid crystals activate the NALP3 inflammasome , 2006, Nature.

[71]  M. Imazio,et al.  Colchicine in Addition to Conventional Therapy for Acute Pericarditis: Results of the COlchicine for acute PEricarditis (COPE) Trial , 2005, Circulation.

[72]  M. Imazio,et al.  Colchicine as first-choice therapy for recurrent pericarditis: results of the CORE (COlchicine for REcurrent pericarditis) trial. , 2005, Archives of internal medicine.

[73]  J. Pugin,et al.  Is Dressler syndrome dead? , 2004, Chest.

[74]  Y. Adler,et al.  Colchicine for the Prevention of Postpericardiotomy Syndrome , 2002, Herz.

[75]  J. Fox,et al.  Cytoskeletal Proteins and Platelet Signaling , 2001, Thrombosis and Haemostasis.

[76]  P. Souček,et al.  Colchicine biotransformation by human liver microsomes. Identification of CYP3A4 as the major isoform responsible for colchicine demethylation. , 1997, Biochemical pharmacology.

[77]  W. Jusko,et al.  Oral Absorption Characteristics and Pharmacokinetics of Colchicine in Healthy Volunteers after Single and Multiple Doses , 1996, Journal of clinical pharmacology.

[78]  W. O’Neill,et al.  Combination of lovastatin, enalapril, and colchicine does not prevent restenosis after percutaneous transluminal coronary angioplasty. , 1995, The American journal of cardiology.

[79]  G. Weissmann,et al.  Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils. , 1995, The Journal of clinical investigation.

[80]  P. Hung,et al.  Colchicine disposition in human leukocytes after single and multiple oral administration , 1993, Clinical pharmacology and therapeutics.

[81]  J. O’Keefe,et al.  Ineffectiveness of colchicine for the prevention of restenosis after coronary angioplasty. , 1992, Journal of the American College of Cardiology.

[82]  E. Topol,et al.  Colchicine and antineoplastic therapy for the prevention of restenosis after percutaneous coronary interventions. , 1991, Journal of the American College of Cardiology.

[83]  A. D. Luna,et al.  COLCHICINE FOR RECURRENT PERICARDITIS , 1987, The Lancet.

[84]  J. E. Caner,et al.  Colchicine inhibition of chemotaxis. , 1965, Arthritis and rheumatism.

[85]  which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Modulation of Monosodium Urate Crystal-induced Responses in Neutrophils by the Myeloid Inhibitory C-type Lectin-like Receptor: Pote , 2013 .

[86]  K. Aziz,et al.  Cholesterol crystals rupture biological membranes and human plaques during acute cardiovascular events--a novel insight into plaque rupture by scanning electron microscopy. , 2006, Scanning.

[87]  D. Kaul,et al.  Effect of trifluoperazine and colchicine on smooth muscle cellular proliferative and secretory activity induced by hypercholesterolemic medium in vitro. , 1990, Biochemistry international.