EClinicalMedicine (Oct 2024)

Colchicine for secondary prevention of ischaemic stroke and atherosclerotic events: a meta-analysis of randomised trialsResearch in context

  • Aernoud T.L. Fiolet,
  • Michiel H.F. Poorthuis,
  • Tjerk S.J. Opstal,
  • Pierre Amarenco,
  • Kevin Emery Boczar,
  • Ian Buysschaert,
  • Charley Budgeon,
  • Noel C. Chan,
  • Jan H. Cornel,
  • Sanjit S. Jolly,
  • Jamie Layland,
  • Robin Lemmens,
  • Nathan Mewton,
  • Stefan M. Nidorf,
  • Domingo A. Pascual-Figal,
  • Christopher Price,
  • Binita Shah,
  • Jean-Claude Tardif,
  • Peter L. Thompson,
  • Jan G.P. Tijssen,
  • Georgios Tsivgoulis,
  • Cathal Walsh,
  • Yongjun Wang,
  • Christian Weimar,
  • John W. Eikelboom,
  • Arend Mosterd,
  • Peter J. Kelly

Journal volume & issue
Vol. 76
p. 102835

Abstract

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Summary: Background: Guidelines recommend low-dose colchicine for secondary prevention in cardiovascular disease, but uncertainty remains concerning its efficacy for stroke, efficacy in key subgroups and about uncommon but serious safety outcomes. Methods: In this trial-level meta-analysis, we searched bibliographic databases and trial registries form inception to May 16, 2024. We included randomised trials of colchicine for secondary prevention of ischaemic stroke and major adverse cardiovascular events (MACE: ischaemic stroke, myocardial infarction, coronary revascularisation, or cardiovascular death). Secondary outcomes were serious safety outcomes and mortality. A fixed-effect inverse-variance model was used to generate a pooled estimate of relative risk (RR) with 95% confidence intervals (CI). This study is registered with PROSPERO, CRD42024540320. Findings: Six trials involving 14,934 patients with prior stroke or coronary disease were included. In all patients, colchicine compared with placebo or no colchicine reduced the risk for ischaemic stroke by 27% (132 [1.8%] events versus 186 [2.5%] events, RR 0.73 [95% CI 0.58–0.90]) and MACE by 27% (505 [6.8%] events versus 693 [9.4%] events, with RR 0.73 [0.65–0.81]). Efficacy was consistent in key subgroups (females versus males, age below versus above 70, with versus without diabetes, statin versus non-statin users). Colchicine was not associated with an increase in serious safety outcomes: hospitalisation for pneumonia (109 [1.5%] versus 106 [1.5%], RR 0.99 [0.76–1.30]), cancer (247 [3.5%] versus 255 [3.6%], RR 0.97 [0.82–1.15]), and gastro-intestinal events (153 [2.1%] versus 135 [1.9%]), RR 1.15 [0.91–1.44]. There was no difference in all-cause death (201 [2.7%] versus 181 [2.4%], RR 1.09 [0.89–1.33]), cardiovascular death (70 [0.9%] versus 80 [1.1%], RR 0.89 [0.65–1.23]), or non-cardiovascular death (131 [1.8%] versus 101 [1.4%], RR 1.26 [0.98–1.64]). Interpretation: In patients with prior stroke or coronary disease, colchicine reduced ischaemic stroke and MACE, with consistent treatment effect in key subgroups, and did not increase serious safety events or death. Funding: There was no funding source for this study.

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