Colchicine: A Versatile Anti-Inflammatory Medication for Cardiovascular Disease

General Description

Colchicine has shown clinical efficacy in the treatment of pericardial disease, specifically acute and recurrent pericarditis. It is recommended as a first-line therapy by the European Society of Cardiology. Limited data exists regarding pericarditis with concurrent myocardial injury, and further research is needed in this area. In the management of atrial fibrillation (AF), colchicine has potential applications by targeting the NLRP3 inflammasome cascade. It has been found to reduce the incidence of AF in post-operative settings and has shown promise in reducing AF recurrence after ablation procedures. While there are no specific guidelines, colchicine use is recommended for pericardial symptoms after ablation. Colchicine is generally well-tolerated, with common side effects including gastrointestinal intolerance and myalgias. Adjustments in dosage and treatment duration can improve tolerability, and serious side effects are rare. Consideration of individual patient factors is important for optimal use.

Figure 1. Tablets of colchicine

Colchicine in Cardiovascular Disease

Pericardial disease

Colchicine is a medication used in the treatment of acute and recurrent pericarditis, a condition characterized by inflammation of the pericardium. The pericardium, being richly innervated, often leads to disabling or recurrent chest pain in cases of pericarditis. Clinical trials have been conducted to evaluate the efficacy of colchicine in both acute and recurrent pericarditis. These studies involved a loading dose of 1-2 mg followed by a daily maintenance dose of 0.5-1 mg for varying durations, with longer treatments for chronic or recurrent cases. Most of these trials, although small in size, yielded favorable results, except for a contradicting study. While most research focused on isolated pericarditis, limited data exists regarding pericarditis with concurrent myocardial injury. Currently, the European Society of Cardiology guidelines recommend colchicine as a first-line treatment for both acute and recurrent pericarditis, alongside conventional anti-inflammatory regimens such as aspirin or non-steroidal anti-inflammatory drugs. However, the American College of Cardiology/American Heart Association guidelines only recommend colchicine for pericarditis after myocardial infarction. Colchicine treatment is typically administered for 1-3 months in acute cases and at least 6 months in recurrent cases, regardless of inflammatory markers or symptoms. In summary, colchicine has demonstrated efficacy in the treatment of acute and recurrent pericarditis and is recommended as a first-line therapy by the European Society of Cardiology. Further research is needed to explore its effectiveness in pericarditis with concurrent myocardial injury. ¹

Atrial fibrillation

Colchicine, an anti-inflammatory medication, has shown potential clinical applications in the management of atrial fibrillation (AF). Inflammation, specifically the activation of the NLRP3 inflammasome and subsequent secretion of inflammatory cytokines, has been implicated in the occurrence and progression of AF. Increased levels of inflammatory markers have been associated with post-operative AF (POAF), which can lead to complications such as stroke and prolonged hospital stays. Colchicine has been found to suppress POAF by targeting the NLRP3 inflammasome cascade. A meta-analysis of three large double-blind randomized controlled trials demonstrated that peri-operative colchicine reduced the incidence of AF by 35% in over 900 patients. However, smaller open-label studies with shorter follow-up periods did not show significant results. Despite some discrepancies, ACC/AHA guidelines suggest considering colchicine for post-operative AF prevention. In the context of post-ablation AF, colchicine has shown promise in reducing AF recurrence after radiofrequency ablation pulmonary vein isolation procedures. Limited evidence suggests that a 3-month regimen of colchicine resulted in decreased AF recurrence, improved quality of life, and reduced levels of inflammatory markers. While there are currently no recommendations from scientific society guidelines, the use of colchicine is recommended for pericardial symptoms after ablation. Ongoing studies are further investigating the potential benefits of colchicine in POAF and post-ablation AF management. ²

Dosage, Side Effects, and Safety Considerations

Colchicine is a medication used for acute gout and chronic prevention. It exhibits dose-dependent effects, and most side effects can be reversed by reducing the dose or stopping treatment. Higher doses are approved for patients without advanced kidney disease, but a lower dose regimen has shown similar effectiveness with improved tolerability. The common adverse effects of colchicine include gastrointestinal intolerance and myalgias. Lower daily doses and longer treatment durations can help reduce gastrointestinal issues. Very high doses over prolonged periods may lead to more serious side effects such as myelosuppression, neuromuscular toxicity, liver damage, and dermatological problems. Safety analyses have not shown increased mortality or major adverse events related to colchicine. However, real-world scenarios with patients having multiple health conditions and taking other medications were not fully considered in these studies. Dose adjustments are necessary for patients with chronic kidney disease to avoid toxic accumulation. Strong inhibitors of CYP3A4 and P-glycoprotein pathways should be avoided as they increase colchicine concentrations. Certain cardiac medications may also require lower colchicine doses. Fatalities related to colchicine are rare and usually associated with suicide attempts or advanced organ dysfunction combined with strong P-glycoprotein inhibitors. Contraindications exist for patients using potent CYP3A4 or P-glycoprotein inhibitors with renal or hepatic impairment. Overall, colchicine's tolerability can be improved by using lower doses, longer treatment durations, and considering individual patient factors such as renal function and concurrent medications. ³

Reference

1. Adler Y, Charron P, Imazio M, Badano L, Barón-Esquivias G, Bogaert J, Brucato A, Gueret P, Klingel K, Lionis C, Maisch B, Mayosi B, Pavie A, Ristic AD, Sabaté Tenas M, Seferovic P, Swedberg K, Tomkowski W; ESC Scientific Document Group. 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 Nov 7;36(42):2921-2964.

2. Deftereos SG, Beerkens FJ, Shah B, Giannopoulos G, Vrachatis DA, Giotaki SG, Siasos G, Nicolas J, Arnott C, Patel S, Parsons M, Tardif JC, Kovacic JC, Dangas GD. Colchicine in Cardiovascular Disease: In-Depth Review. Circulation. 2022 Jan 4;145(1):61-78.

3. Imazio M, Nidorf M. Colchicine and the heart. Eur Heart J. 2021 Jul 21;42(28):2745-2760.

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