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Effectiveness of Simvastatin Versus Gemfibrozil for Primary Prevention of Cardiovascular Events: A Retrospective Cohort Study of 223,699 Primary Care Patients

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Abstract

Background and Objective

Evidence of the effectiveness of statins compared with fibrates for primary prevention of cardiovascular events is limited. Therefore, we assessed the comparative effectiveness of simvastatin versus gemfibrozil for primary prevention of major adverse cardiovascular events (MACE) and mortality.

Methods

This territory-wide cohort study used electronic health records of simvastatin and gemfibrozil prescriptions from the Hong Kong Hospital Authority and compared simvastatin or gemfibrozil initiation. The primary outcome was MACE, defined as the composite of the first diagnosis of cardiovascular mortality, coronary heart disease, or stroke. Secondary outcomes were the individual components of MACE, all-cause mortality, and non-cardiovascular mortality. Inverse probability of treatment weighting on the propensity score was used to estimate hazard ratios (HRs).

Results

A total of 223,699 individuals (120,207 [53.7%] women; median follow-up 7.0 years [interquartile range 5.7–9.1]) who were prescribed simvastatin (n = 168,630) or gemfibrozil (n = 55,069) were included. Simvastatin was associated with a reduced risk of MACE (HR 0.90, 95% confidence interval [CI] 0.88–0.93), all-cause mortality (HR 0.88, 95% CI 0.86–0.90), cardiovascular mortality (HR 0.71, 95% CI 0.67–0.76), and non-cardiovascular mortality (HR 0.92, 95% CI 0.89–0.95). Associations for MACE varied according to baseline characteristics with gemfibrozil being associated with a reduced risk of MACE in men and patients with low baseline high-density lipoprotein (HDL) cholesterol (< 1.0 mmol/L).

Conclusion

The results of this study showed better population-level effectiveness of simvastatin compared with gemfibrozil for the primary prevention of MACE; however, a definitive randomized controlled trial is required to compare simvastatin with gemfibrozil among patients with low HDL cholesterol, as they appear to obtain benefit with gemfibrozil.

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Acknowledgements

The computations were performed using research computing facilities offered by Information Technology Services, the University of Hong Kong. Joseph E. Blais was supported by the Hong Kong Research Grants Council as a recipient of the Hong Kong PhD Fellowship Scheme. The authors thank Dr Stephen Weng for his feedback on an earlier draft of this paper.

Author information

Authors and Affiliations

  1. Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, General Office, L02-56 2/F, Laboratory Block LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China

    Joseph E. Blais, Xuxiao Ye, Eric Y. F. Wan, Ian C. K. Wong & Esther W. Chan

  2. School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China

    Joseph E. Blais

  3. Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China

    Eric Y. F. Wan & William C. W. Wong

  4. Laboratory of Data Discovery for Health, Hong Kong Science Park, Sha Tin, Hong Kong SAR, China

    Eric Y. F. Wan, Ian C. K. Wong & Esther W. Chan

  5. Department of General Practice, HKU-Shenzhen Hospital, Shenzhen, China

    William C. W. Wong

  6. Research Department of Practice and Policy, UCL School of Pharmacy, London, UK

    Ian C. K. Wong

  7. Faculty of Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China

    Brian Tomlinson

  8. The University of Hong Kong Shenzhen Institute of Research and Innovation, Shenzhen, Hong Kong SAR, China

    Esther W. Chan

  9. Department of Pharmacy, HKU-Shenzhen Hospital, Shenzhen, China

    Esther W. Chan

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  1. Joseph E. Blais
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  7. Esther W. Chan
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Corresponding author

Correspondence to Esther W. Chan.

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Funding

This study was not funded.

Conflict of interest

Joseph E. Blais, Xuxiao Ye, Eric Y.F. Wan, William C.W. Wong, Ian C.K. Wong, Brian Tomlinson, and Esther W. Chan have no relevant financial or non-financial interests to disclose.

Ethics approval

This study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (reference number: UW17-135).

Consent to participate

This is an observational study and informed consent was waived by the Institutional Review Board.

Consent for publication

Not applicable.

Data availability

The data used for this study are confidential and are not available for sharing.

Code availability

Not applicable.

Author contributions

JEB and XY had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis. Conceptualization: JEB, EWC, BT. Formal analysis: JEB, XY. Validation: XY. Resources: EWC, ICKW. Software: EYFW. Visualization: JEB. Supervision: EWC, ICKW. Writing—original draft: JEB. Writing—review and editing of the manuscript for important intellectual content: All authors.

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Blais, J.E., Ye, X., Wan, E.Y.F. et al. Effectiveness of Simvastatin Versus Gemfibrozil for Primary Prevention of Cardiovascular Events: A Retrospective Cohort Study of 223,699 Primary Care Patients. Clin Drug Investig 42, 987–997 (2022). https://doi.org/10.1007/s40261-022-01208-9

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