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Colchicine in atherosclerotic cardiovascular disease
  1. Bradley Tucker1,2,
  2. Neil Goonetilleke3,
  3. Sanjay Patel1,4,
  4. Anthony Keech1,4
  1. 1Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
  2. 2Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia
  3. 3Dubbo Base Hospital, Dubbo, New South Wales, Australia
  4. 4NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia
  1. Correspondence to Professor Anthony Keech, NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia; anthony.keech{at}sydney.edu.au

Abstract

Inflammation has a direct role in the development of atherosclerotic vascular disease, and oral colchicine displays broad anti-inflammatory properties. Several large, randomised controlled trials (RCTs) have evaluated colchicine’s impact on cardiovascular outcomes. Results from a meta-analysis of these trials demonstrate that colchicine reduces the risk of recurrent major adverse cardiovascular events (MACEs) by 25%, leading to its recent approval by the Food and Drug Administration for the treatment and prevention of cardiovascular disease. Despite this, colchicine has not been shown to confer any survival benefit in these trials. The non-significant reduction in cardiovascular death of 18% (95% CI: 45% decrease to 23% increase) is outweighed by a more prominent, borderline non-significant increase in the risk of non-cardiovascular death by 38% (95% CI: 1% decrease to 92% increase). Key populations including those with heart failure, those undergoing surgical revascularisation, women, elderly individuals and non-Caucasians are under-represented in completed trials, which limits generalisability. C reactive protein has been proposed as a biomarker for colchicine response and shows promise for identifying a high-risk population where the benefit on MACE reduction and specifically reduced cardiovascular death might outweigh any real increased risk of non-cardiovascular death; however, this approach is still to be validated in ongoing RCTs. In conclusion, while colchicine shows promise in reducing MACE, its net risk–benefit profile requires further elucidation before its widespread adoption into clinical practice for the secondary prevention of atherosclerotic cardiovascular disease. Much more large-scale, long-term trial data are still needed in this space.

  • Coronary Artery Disease
  • Atherosclerosis
  • Acute Coronary Syndrome
  • Inflammation
  • Stroke

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Footnotes

  • Contributors The authors confirm contribution to the paper as follows: Study conception and design: AK and SP. Literature review: BT and NG. Draft manuscript preparation with input from all authors: BT and NG. Final manuscript preparation and submission: BT and AK. All authors reviewed and approved the final version of the manuscript.

  • Funding SP is supported for this work by a Clinical Trials Centre Future Fellowship from the Faculty of Medicine and Health, The University of Sydney. AK is supported by a National Health and Medical Research Council Senior Principal Research Fellowship (APPID 2018537) and the Faculty of Medicine and Health, The University of Sydney.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.