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Drug-drug interactions between vitamin K antagonists and statins: a systematic review

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Abstract

Purpose

Concomitant use of vitamin K antagonists (VKA) and statins is frequent in cardiovascular patients. However, clinical guidelines on this drug combination are divergent. Therefore, we performed a systematic review to evaluate the effect of statin initiation on coagulation among VKA users.

Methods

Following the PRISMA guidelines, we applied two broad search strategies for the drug interaction between VKA and statins in both Embase and Pubmed; 8623 unique hits were obtained. In the final sample, eight studies were included.

Results

The most frequently used VKA in the studies was warfarin, while simvastatin was the most commonly initiated statin. All included studies showed a minor increase in the anticoagulant effect of VKA following statin initiation during VKA treatment. The reported increases in mean international normalized ratio (INR) ranged from 0.15–0.65.

Conclusion

The anticoagulant effect of statin initiation in patients treated with VKA is likely to be of limited clinical relevance but should be evaluated individually.

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Data availability

All data generated or analyzed during this study are available from the corresponding author on reasonable request.

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Acknowledgments

The authors acknowledge Alaa Burghle for the help with guidance to Covidence.

Funding

TBS reports personal fees from Pfizer, Eisai, and Astellas Pharma, outside the submitted work. TBS has done consulting and paid lectures for Pfizer and paid lectures for Eisai and Astellas Pharma with no relation to the submitted work. AP reports participation in research projects funded by Alcon, Almirall, Astellas, Astra-Zeneca, Boehringer-Ingelheim, Novo Nordisk, Servier, and LEO Pharma, all with funds paid to the institution where he was employed (no personal fees) and with no relation to the work.

Author information

Authors and Affiliations

  1. Department of Clinical Biochemistry, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, 2650, Hvidovre, Denmark

    Anna E. Engell & Bent S. Lind

  2. Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark

    Andreas L. O. Svendsen

  3. Copenhagen Primary Care Laboratory (CopLab) Database, Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark

    Bent S. Lind

  4. Clinical Pharmacology and Pharmacy, Department of Public health, University of Southern Denmark, Odense, Denmark

    Tore Bjerregaard Stage, Maja Hellfritzsch & Anton Pottegård

  5. Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark

    Maja Hellfritzsch

Authors
  1. Anna E. Engell
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  3. Bent S. Lind
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  5. Maja Hellfritzsch
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  6. Anton Pottegård
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Contributions

All authors contributed to the study and design. The literature search was performed by Andreas L. O. Svendsen. Data was selected and extracted by Andreas L. O. Svendsen and Anna E. Engell. The first draft of the manuscript was written by Anna E. Engell and Anton Pottegård supervised the work. All authors commented on previous versions of the manuscript and read and approved the final manuscript.

Corresponding author

Correspondence to Anna E. Engell.

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Engell, A.E., Svendsen, A.L.O., Lind, B.S. et al. Drug-drug interactions between vitamin K antagonists and statins: a systematic review. Eur J Clin Pharmacol 77, 1435–1441 (2021). https://doi.org/10.1007/s00228-020-03074-w

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