title: Colchicine for prevention of cardiovascular events.
abstract: BACKGROUND
  Colchicine is an anti-inflammatory drug that is used for a wide range of inflammatory diseases. Cardiovascular disease also has an inflammatory component but the effects of colchicine on cardiovascular outcomes remain unclear. Previous safety analyses were restricted to specific patient populations.
  
  
  OBJECTIVE
  To evaluate potential cardiovascular benefits and harms of a continuous long-term treatment with colchicine in any population, and specifically in people with high cardiovascular risk.
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ClinicalTrials.gov, WHO International Clinical Trials Registry, citations of key papers, and study references in January 2015. We also contacted investigators to gain unpublished data.
  
  
  METHODS
  Randomised controlled trials (parallel-group or cluster design or first phases of cross-over studies) comparing colchicine over at least six months versus any control in any adult population.
  
  
  METHODS
  Primary outcomes were all-cause mortality, myocardial infarction, and adverse events. Secondary outcomes were cardiovascular mortality, stroke, heart failure, non-scheduled hospitalisations, and non-scheduled cardiovascular interventions. We conducted predefined subgroup analyses, in particular for participants with high cardiovascular risk. .
  
  
  RESULTS
  We included 39 randomised parallel-group trials with 4992 participants. Colchicine had no effect on all-cause mortality (RR 0.94, 95% CI 0.82 to 1.09; participants = 4174; studies = 30; I² = 27%; moderate quality of evidence). There is uncertainty surrounding the effect of colchicine in reducing cardiovascular mortality (RR 0.34, 95% CI 0.09 to 1.21, I² = 9%; participants = 1132; studies = 7; moderate quality of evidence). Colchicine reduced the risk for total myocardial infarction (RR 0.20, 95% CI 0.07 to 0.57; participants = 652; studies = 2; moderate quality of evidence). There was no effect on total adverse events (RR 1.52, 95% CI 0.93 to 2.46; participants = 1313; studies = 11; I² = 45%; very low quality of evidence) but gastrointestinal intolerance was increased (RR 1.83, 95% CI 1.03 to 3.26; participants = 1258; studies = 11; I² = 74%; low quality of evidence). Colchicine showed no effect on heart failure (RR 0.62, 95% CI 0.10 to 3.88; participants = 462; studies = 3; I² = 45%; low quality of evidence) and no effect on stroke (RR 0.38, 95% CI 0.09 to 1.70; participants = 874; studies = 3; I² = 45%; low quality of evidence). Reporting of serious adverse events was inconsistent; no event occurred over 824 patient-years (4 trials). Effects on other outcomes were very uncertain. Summary effects of RCTs specifically focusing on participants with high cardiovascular risk were similar (4 trials; 1230 participants).
  
  
  CONCLUSIONS
  There is much uncertainty surrounding the benefits and harms of colchicine treatment. Colchicine may have substantial benefits in reducing myocardial infarction in selected high-risk populations but uncertainty about the size of the effect on survival and other cardiovascular outcomes is high, especially in the general population from which most of the studies in our review were drawn. Colchicine is associated with gastrointestinal side effects based on low-quality evidence. More evidence from large-scale randomised trials is needed.
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Spitalstrasse 12, Basel, Switzerland, CH-4031.
authors.forename: Lars G
authors.initials: LG
authors.lastname: Hemkens
authors.forename: Hannah
authors.initials: H
authors.lastname: Ewald
authors.forename: Viktoria L
authors.initials: VL
authors.lastname: Gloy
authors.forename: Armon
authors.initials: A
authors.lastname: Arpagaus
authors.forename: Kelechi K
authors.initials: KK
authors.lastname: Olu
authors.forename: Mark
authors.initials: M
authors.lastname: Nidorf
authors.forename: Dominik
authors.initials: D
authors.lastname: Glinz
authors.forename: Alain J
authors.initials: AJ
authors.lastname: Nordmann
authors.forename: Matthias
authors.initials: M
authors.lastname: Briel
mesh_terms: D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D002423:Cause of Death; D003078:Colchicine / Q000009:adverse effects / Q000627:therapeutic use*; D006333:Heart Failure / Q000517:prevention & control; D006801:Humans; D009203:Myocardial Infarction / Q000401:mortality / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D020521:Stroke / Q000401:mortality / Q000517:prevention & control
chemical_list: D000893:Anti-Inflammatory Agents; D003078:Colchicine
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