title: Cardiovascular effects and safety of long-term colchicine treatment: Cochrane review and meta-analysis.
abstract: 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 6 months 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 1 mg/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.
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
authors.forename: Lars G
authors.initials: LG
authors.lastname: Hemkens
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
authors.forename: Hannah
authors.initials: H
authors.lastname: Ewald
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
authors.forename: Viktoria L
authors.initials: VL
authors.lastname: Gloy
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
authors.forename: Armon
authors.initials: A
authors.lastname: Arpagaus
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
authors.forename: Kelechi K
authors.initials: KK
authors.lastname: Olu
authors.affiliation: Heart Care Western Australia, Perth, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Nidorf
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Glinz
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
authors.forename: Alain J
authors.initials: AJ
authors.lastname: Nordmann
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland Department of Clinical Research, University of Basel, Basel, Switzerland Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Matthias
authors.initials: M
authors.lastname: Briel
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000401:mortality; D003078:Colchicine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D009203:Myocardial Infarction / Q000517:prevention & control; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003078:Colchicine