Colchicine and the heart

Колхицин и сердце
Massimo Imazio, Mark Nidorf
2021-03-29

anti-inflammatory therapycardiovascular diseasecolchicinecoronary syndromespericarditis recurrence
Colchicine is a unique, sophisticated anti-inflammatory agent that has been used for decades for the prevention of acute inflammatory flares in gout and familial Mediterranean fever. In recent years, clinical trials have demonstrated its potential in a range of cardiovascular (CV) conditions. Colchicine is avidly taken up by leucocytes, and its ability to bind to tubulin and interfere with microtubular function affects the expression of cytokines and interleukins, and the ability of neutrophils to marginate, ingress, aggregate, express superoxide, release neutrophil extracellular traps, and interact with platelets. In patients with acute and recurrent pericarditis, clinical trials in >1600 patients have consistently shown that colchicine halves the risk of recurrence [relative risk (RR) 0.50, 95% confidence interval (CI) 0.42-0.60]. In patients with acute and chronic coronary syndromes, multicentre randomized controlled trials in >11 000 patients followed for up to 5 years demonstrated that colchicine may reduce the risk of CV death, myocardial infarction, ischaemic stroke and ischaemia-driven revascularization by >30% (RR 0.63, 95% CI 0.49-0.81). The use of colchicine at doses of 0.5-1.0 mg daily in CV trials has proved safe. Early gastrointestinal intolerance limits its use in ∼10% of patients; however, ∼90% of patients tolerate it well over the long term. Despite isolated case reports, clinically relevant drug interactions with moderate to strong CYP3A4 inhibitors/competitors or P-glycoprotein inhibitors/competitors are rare if this dosage of colchicine is used in the absence of advanced renal or liver disease. The aim of this review is to summarize the contemporary data supporting the efficacy and safety of colchicine in patients with CV disease.
1
Across more than 1,600 patients with acute or recurrent pericarditis, colchicine consistently halved recurrence risk (RR 0.50, 95% CI 0.42–0.60).
2
Cardiovascular trials found daily colchicine doses of 0.5–1.0 mg generally safe, with early gastrointestinal intolerance limiting treatment in approximately 10% of patients.
3
Clinically relevant interactions with CYP3A4 or P-glycoprotein inhibitors are rare at cardiovascular doses when advanced renal or liver disease is absent.
4
Colchicine’s anti-inflammatory effects arise from tubulin binding, altering cytokine signaling and neutrophil–platelet inflammatory interactions.
5
In over 11,000 patients with acute or chronic coronary syndromes, colchicine reduced major cardiovascular outcomes by more than 30% (RR 0.63, 95% CI 0.49–0.81).

Colchicine use in patients with cardiovascular disease, including pericarditis and acute or chronic coronary syndromes

The efficacy and safety of colchicine, including its anti-inflammatory mechanisms, prevention of pericarditis recurrence, reduction of cardiovascular events, tolerability, and drug-interaction risks

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2021-03-29
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Massimo Imazio
Mark Nidorf
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