Colchicine efficacy and safety for the treatment of cardiovascular diseases

Abstract

The emerging role of colchicine in the treatment of cardiovascular diseases is a strong demand for a comprehensive understanding of its efficacy and safety. This meta-analysis and systematic review aimed to study the efficacy in the reduction of adverse cardiovascular outcomes (CO), and the risk of colchicine-related adverse events (CRAEs). Fourteen thousand and nine eighty three patients from 22 randomized controlled trials (RCTs) were included, 9 in patients with coronary artery disease-CAD, 9 in patients with pericarditis, 4 in patients with atrial fibrillation-AF or heart failure. Colchicine was efficacious in the reduction of adverse CO across different settings: pericardial diseases (reduced risk of recurrent pericarditis, 17.6% vs. 35%, RR 0.50, 95% CI 0.41-0.61), CAD (reduced risk of cardiac death, myocardial infarction, stroke,coronary revascularization or hospitalization, 6.1% vs. 8.5%, RR 0.73, 95% CI 0.64-0.83), AF (reduced risk of arrhythmia recurrence, 14.2% vs. 22.7%, RR 0.62, 95% CI 0.44-0.88). Colchicine was associated with increased risk of gastrointestinal CRAEs (11.2% vs. 8.8%, RR 1.87, 95% CI 1.41-2.47) and drug discontinuation (5.4% vs. 3.7%, RR 1.58, 95% CI 1.25-1.99). In both cases, the risk was proportional to the daily dose or duration of treatment, possibly due to early drug discontinuation or tolerance. Other CRAEs (muscle-related, liver,hematologic,cutaneous, infections) were not increased by colchicine, as long as all-cause death (2.2% vs. 1.9%, RR 1.11, 95% CI 0.79-1.54) or non-cardiovascular death (1.5% vs. 1%, RR 1.43, 95% CI 0.93-2.19). Colchicine is efficacious and safe for the treatment of cardiovascular diseases. The risk of gastrointestinal CRAEs and drug discontinuation is not significant if colchicine is used at lower doses (0.5 mg daily) or for longer periods of time (> 6 months).

Keywords: Adverse events; Atrial fibrillation; Colchicine; Coronary artery disease; Heart failure; Pericarditis.

Fig. 1

Forest plot showing colchicine efficacy in the reduction of adverse cardiovascular outcomes, according to the clinical setting

Fig. 2

Forest plot showing the risk of gastrointestinal CRAE with colchicine treatment compared with placebo

Fig. 3

Forest plots showing the risk of gastrointestinal CRAE with colchicine treatment compared with placebo, according to treatment duration (left) and daily dose (right)

Fig. 4

Forest plots showing the risk of all-cause death and non-cardiovascular death with colchicine treatment compared with placebo

Fig. 5

Forest plots showing the risk of colchicine discontinuation