Colchicine and the Heart: Pushing the Envelope

Perspective:

This exuberant review summarizes the biochemical characteristics of colchicine, its mechanism of action, and side effects, and what is currently known about the role of colchicine in cardiovascular medicine including and beyond pericardial disease. The following are points to remember:

1. History. Colchicine is an old drug, traditionally considered a staple therapy for gout and a second-line treatment for pericarditis, as well as a basic part of disease management for familial Mediterranean fever and Behcet's disease.

2. Mechanism of action. Colchicine typically is classified as an anti-inflammatory agent, although its mechanism of action does not involve the arachidonic acid pathway. Colchicine inhibits microtubule polymerization by binding to tubulin, affecting any process that requires cytoskeletal changes––including cell mitosis and neutrophil motility.

3. Side effects. A significant percentage of patients report adverse effects, mainly gastrointestinal symptoms, serious enough to cause discontinuation of therapy even at low daily doses. However, in patients who tolerate colchicine, it can be administered for long periods of time without any notable long-term side effects. Rare side effects of chronic colchicine administration include liver failure; bone marrow depression, which may manifest as leucopenia or aplastic anemia; and rhabdomyolysis.

4. Colchicine and pericarditis. In the Colchicine in Acute Pericarditis (COPE) and Colchicine for Recurrent Pericarditis (CORE) trials, colchicine as an adjunct therapy was found to be an effective addition to nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of acute pericarditis. The use of colchicine was associated with faster symptomatic relief than with NSAIDs alone, and with lower rates of recurrent pericarditis.

5. Postoperative atrial fibrillation. In a substudy of the Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) trial, colchicine administered from postoperative day 3 and for up to 1 month after surgery, was associated with a 45% reduction in the incidence of postoperative atrial fibrillation, and was associated with a reduced duration of postoperative atrial fibrillation episodes.

6. Recurrent atrial fibrillation following ablation. A substudy of the COPPS trial found that the rate of recurrent atrial fibrillation after pulmonary vein isolation was lower in association with colchicine monotherapy for 3 months (16% vs. 33.5% with placebo).

7. Colchicine in coronary artery disease (CAD). Colchicine treatment has been associated with a reduction in levels of high-sensitivity C-reactive protein. One prospective trial (the LoDoCo study) found that continuous treatment with colchicine in addition to standard therapy among patients with stable CAD was associated with a lower rate of the composite endpoint of acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic stroke (5.3% vs. 16% at 3 years). The authors noted that colchicine therapy might be associated with a reduction in biomarkers related to vascular injury that is independent of suppression of inflammation.

8. Colchicine and percutaneous coronary intervention. In one study, in-stent restenosis detected by intravascular ultrasound at 6 months was less common after bare-metal stent placement in diabetic patients when colchicine was administered.

9. Other preclinical data. Colchicine has been shown to attenuate the left ventricular response to pressure-overload heart failure in dogs and in rats, to reduce myocardial cell stiffness in normal rat cardiomyocytes, and to increase calcium currents in rat cardiac cells. The authors state that these findings suggest possible new areas for the study of colchicine in the treatment of arrhythmia, cardiac hypertrophy, and heart failure.

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Pericardial Disease, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Lipid Metabolism, Acute Heart Failure, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Vascular Medicine

Keywords: Cytoskeleton, Liver Failure, Gout, Coronary Artery Disease, Leukopenia, Coronary Disease, Depression, Inflammation, Acute Coronary Syndrome, Stroke, Pancytopenia, Colchicine, Behcet Syndrome, Postpericardiotomy Syndrome, Pericarditis, Rhabdomyolysis, Stents, Percutaneous Coronary Intervention, Postoperative Period, Cardiomegaly, Vascular System Injuries, Heart Diseases, Bone Marrow, Out-of-Hospital Cardiac Arrest, Familial Mediterranean Fever, Heart Failure, Catheter Ablation, Arachidonic Acid, Diabetes Mellitus


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