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Effects of Colchicine on Cardiovascular Outcomes in Patients with Coronary Artery Disease: A Systematic Review and One-Stage and Two-Stage Meta-Analysis of Randomized-Controlled Trials

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Abstract

Aim

Colchicine has received emerging interest due to its cardiovascular benefits in patients with coronary artery disease (CAD). We conducted a one-stage meta-analysis of reconstructed individual patient data (IPD) from randomized-controlled trials to summarize the effects of colchicine on cardiovascular outcomes in patients with CAD.

Methods

Four databases (PubMed, Embase, Cochrane, SCOPUS) were searched for articles published from inception to 30th September 2020, examining the effect of colchicine on cardiovascular outcomes in patients with CAD, yielding 10 randomized-controlled trials with a combined cohort of 12,781 patients. IPD was reconstructed from Kaplan–Meier curves published in 3 studies and analysed using the shared-frailty Cox model. Aggregate data meta-analysis of all 10 studies was performed for outcomes unsuitable for IPD reconstruction.

Results

In patients receiving colchicine compared to placebo, one-stage meta-analysis demonstrated a hazard ratio of 0.70 (95% CI 0.61–0.80) for the composite outcome of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent hospitalization for angina requiring coronary revascularization. Aggregate data meta-analysis demonstrated a significant reduction in hazard rate for stroke (HR 0.45; 95% CI 0.27–0.75) and urgent revascularization (HR 0.59; 95% CI 0.38–0.91); and a relative risk reduction for myocardial infarction (RR 0.72; 95% CI of 0.52–1.00) and post-operative atrial fibrillation (RR 0.64; 95% CI 0.48–0.86).

Conclusion

Given the significant benefits of colchicine demonstrated on IPD, and its consistent benefits when analyzed using aggregate data meta-analysis, we propose that colchicine may be considered as an additional pharmacological adjunct to the first line therapy for patients with coronary artery disease.

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Abbreviations

CAD:

Coronary artery disease

IPD:

Individual Patient data

PRISMA:

Preferred reporting items of systematic reviews and meta-analyses

MACE:

Major adverse cardiac events

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Authors and Affiliations

  1. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Yao Neng Teo, Yao Hao Teo, Nicholas L. Syn, Ming Wei Goh, Celine Shuen Yin Yoong, Chi-Hang Lee, Mark Yan-Yee Chan, Ping Chai, Tiong-Cheng Yeo & Ching-Hui Sia

  2. Department of Cardiology, National University Heart Centre Singapore, 1E Kent Ridge Road, NUHS Tower Block Level 9, Singapore, 119228, Singapore

    Chi-Hang Lee, Mark Yan-Yee Chan, Ping Chai, Tiong-Cheng Yeo & Ching-Hui Sia

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Correspondence to Ching-Hui Sia.

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Funding

This work was supported by the National University of Singapore Yong Loo Lin School of Medicine’s Junior Academic Faculty Scheme to CS.

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The authors declare that they have no conflict of interest.

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The data used for this study will be shared on reasonable request to the corresponding author.

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The software used for analysis include STATA Version 16.1 and Review Manager Version 5.4.

Author contributions

YNT, YHT, NLS, and CS designed the study and developed the study protocol and tools. YNT, YNT, MWG, and CSYY were responsible for data collection. YNT, YHT, NLS, and CS analyzed data and wrote the manuscript. All authors contributed to the conceptualization of the research questions, interpretation of the results, and manuscript writing and revision. All authors read and approved the final manuscript.

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Teo, Y.N., Teo, Y.H., Syn, N.L. et al. Effects of Colchicine on Cardiovascular Outcomes in Patients with Coronary Artery Disease: A Systematic Review and One-Stage and Two-Stage Meta-Analysis of Randomized-Controlled Trials. High Blood Press Cardiovasc Prev 28, 343–354 (2021). https://doi.org/10.1007/s40292-021-00460-y

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