Cardiovascular effects and safety of long-term colchicine treatment: Cochrane review and meta-analysis

Colchicine is an old anti-inflammatory drug that has shown substantial cardiovascular benefits in recent trials. We systematically reviewed cardiovascular benefits and harms of colchicine in any population and specifically in patients with high cardiovascular risk. We evaluated randomised controlled trials comparing colchicine over at least 6months versus any control in any adult population. Primary outcomes were all-cause mortality, myocardial infarction and adverse events. Cardiovascular mortality was a secondary outcome. We included 39 trials with 4992 patients. The quality of evidence for mortality outcomes and myocardial infarction was moderate but lower for adverse events. Colchicine had no effect on all-cause mortality (RR 0.94, 95% CI 0.82 to 1.09; I-2=27%; 30 trials). Cardiovascular mortality was reduced in some but not all meta-analytical models (random-effects RR 0.34, 0.09 to 1.21, I-2=9%; Peto's OR 0.24, 0.09 to 0.64, I-2=15%; Mantel-Haenszel fixed-effect RR 0.20, 0.06 to 0.68, I-2=0%; 7 trials). The risk for myocardial infarction was reduced (RR 0.20, 0.07 to 0.57; 2 trials). There was no effect on total adverse events (RR 1.52, 0.93 to 2.46, I-2=45%; 11 trials) but gastrointestinal intolerance was increased (RR 1.83, 1.03 to 3.26, I-2=74%; 11 trials). Reporting of serious adverse events was inconsistent; no event occurred over 824 patient-years (4 trials). Effects in high cardiovascular risk populations were similar (4 trials; 1230 patients). We found no evidence supporting colchicine doses above 1mg/day. Colchicine may have substantial cardiovascular benefits; however, there is sufficient uncertainty about its benefit and harm to indicate the need for large-scale trials to further evaluate this inexpensive, promising treatment in cardiovascular disease.