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Association of Metformin with the Mortality and Incidence of Cardiovascular Events in Patients with Pre-existing Cardiovascular Diseases

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Abstract

Introduction

Whether metformin reduces all-cause cardiovascular mortality and the incidence of cardiovascular events in patients with pre-existing cardiovascular diseases (CVD) remains inconclusive. Some randomised controlled trials (RCTs) and cohort studies have shown that metformin is associated with an increased risk of mortality and cardiovascular events.

Methods

We conducted a pooling synthesis to assess the effects of metformin in all-cause cardiovascular mortality and incidence of cardiovascular events in patients with CVD. Studies published up to October 2021 in PubMed or Embase with a registration in PROSPERO (CRD42020189905) were collected. Both RCT and cohort studies were included. Hazard ratios (HR) with 95% CI were pooled across various trials using the random-effects model.

Results

This study enrolled 35 published studies (in 14 publications) for qualitative synthesis and identified 33 studies (published in 26 publications) for quantitative analysis. We analysed a total of 61,704 patients, among them 58,271 patients were used to calculate all-cause mortality while 12,814 patients were used to calculate cardiovascular mortality. Compared with non-metformin control, metformin usage is associated with a reduction in all-cause mortality (HR: 0.90; 95% CI 0.83, 0.98; p = 0.01), cardiovascular mortality (HR: 0.89; 95% CI 0.85, 0.94; p < 0.0001), incidence of coronary revascularisation (HR: 0.79; 95% CI 0.64, 0.98; p = 0.03), and heart failure (HR: 0.90; 95% CI 0.87, 0.94; p < 0.0001) in patients with pre-existing cardiovascular diseases.

Conclusion

Metformin use is associated with a reduction in all-cause mortality, cardiovascular mortality, incidence of coronary revascularisation, and heart failure in patients with CVD; however, metformin usage was not associated with reduction in the incidence of myocardial infarction, angina, or stroke.

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Authors and Affiliations

  1. Department of Physiology and Pathophysiology, Fourth Military Medical University, No. 169 Changle West Rd, Xi’an, 710032, China

    Tian Li, Wenhua Jiang, Manling Liu & Heng Ma

  2. Barts Heart Centre, St. Bartholomew’s Hospital, London, UK

    Rui Providencia

  3. Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

    Lu Yu

  4. Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

    Chunhu Gu

  5. Department of Cardiology and Shanghai Institute of Precision Medicine, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 211125, China

    Alex Chia Yu Chang

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Correspondence to Alex Chia Yu Chang or Heng Ma.

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Funding

National Natural Science Foundation of China (82070261, 91749108, 31671424 and 31571413) and Major Research and Invention Plan of Shaanxi Province, China (2018SF-270, 2018SF-101); Youth Innovation Team of Shaanxi Universities, Shaanxi Province, China. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

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Author’s contribution

Conceptualisation: Heng Ma and Alex Chia Yu Chang. Data curation: Tian Li and Wenhua Jiang. Formal analysis: Tian Li and Rui Providencia. Funding acquisition: Heng Ma and Lu Yu. Investigation: Tian Li. Methodology: Tian Li. Project administration: Tian Li and Heng Ma. Resources: Tian Li, Chunhu Gu. Software: Manling Liu, and Lu Yu. Supervision: Heng Ma and Alex Chia Yu Chang. Validation: Tian Li. Visualisation: Tian Li. Roles/Writing—original draft: Tian Li. Writing—review and editing: Heng Ma and Alex Chia Yu Chang.

Acknowledgements

Providing full text of papers: Beverley Balkau. Providing raw data: Adriaan Kooy.

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Li, T., Providencia, R., Jiang, W. et al. Association of Metformin with the Mortality and Incidence of Cardiovascular Events in Patients with Pre-existing Cardiovascular Diseases. Drugs 82, 311–322 (2022). https://doi.org/10.1007/s40265-021-01665-0

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