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Thromboxane inhibition during concurrent therapy with low-dose aspirin and over-the-counter naproxen sodium

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Abstract

Aspirin is the dominant antiplatelet therapy for cardiovascular disease. Naproxen is frequently used in aspirin-treated patients and may influence the antiplatelet effect of aspirin. We evaluated the pharmacodynamic interaction (lower bound of the one-sided 95% CI for serum TxB2 inhibition < 95%) between 220 mg immediate-release naproxen sodium (once or twice daily) and 81 mg daily immediate release aspirin at various dosing intervals. There was no interaction during the first day of concurrent treatment. After 10 days, irrespective of the timing and dose of naproxen in relation to aspirin dosing, a pharmacodynamic interaction occurred which persisted after discontinuing naproxen. In the control group (aspirin alone), the lower bound for serum TxB2 inhibition was > 98% at all time points. The clinical relevance of these observations remains unknown and merits further investigation since over-the-counter naproxen is widely used to relieve pain by individuals taking low dose aspirin for cardioprotection.

Clinical Trial Registration: NCT02229461

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Acknowledgements

Thanks are given to Alberto Paredes-Diaz, Irene Laurora and Rosa Coppolecchia for their role in protocol development, and to Alberto Paredes-Diaz for overseeing the study and interpretation of the results. The draft manuscript was prepared by a professional medical writer (Deborah Nock, Medical WriteAway, Norwich, UK), with full critical review and approval by all authors.

Funding

This study was sponsored by Bayer HealthCare, Whippany, NJ, USA.

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Authors and Affiliations

  1. Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, 3300 Gallows Road, Falls Church, VA, 22042, USA

    Paul A. Gurbel, Kevin P. Bliden & Udaya S. Tantry

  2. Bayer Consumer HealthCare, Whippany, NJ, USA

    Junhong Zhu, Emanuel Troullos, Robert Centofanti, Sistine Jarvis & Palak Venkataraman

Authors
  1. Paul A. Gurbel
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  2. Kevin P. Bliden
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  3. Junhong Zhu
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  4. Emanuel Troullos
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  5. Robert Centofanti
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  6. Sistine Jarvis
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  7. Palak Venkataraman
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  8. Udaya S. Tantry
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Corresponding author

Correspondence to Paul A. Gurbel.

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Disclosures

Dr. Gurbel reports personal fees from AstraZeneca, Boehringer Ingelheim, Merck, Janssen Pharmaceuticals, Bayer, and Haemonetics; grants from Haemonetics, Merck, Bayer, Duke Clinical Research Institute, Harvard Clinical Research Institute, National Institutes of Health, and Coramed Technologies,; a patent for platelet function testing. Dr. Tantry reports personal fees from Medicure, and Astra Zeneca Dr. Zhu, Mr. Troullos, and Mr. Centofanti, Dr. Jarvis and Dr. Venkataraman are employees of Bayer Consumer HealthCare. Mr. Bliden reports no disclosures.

Ethical approval

The protocol was approved by IntegReview Institutional Review Board before the start of the study. All procedures were conducted in compliance with the ethical principles of the 1964 Declaration of Helsinki and the International Conference on Harmonisation GCP Guidelines and its later amendments or comparable ethical standards.

Informed consent

Healthy volunteers providing written informed consent were enrolled in the study.

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Gurbel, P.A., Bliden, K.P., Zhu, J. et al. Thromboxane inhibition during concurrent therapy with low-dose aspirin and over-the-counter naproxen sodium. J Thromb Thrombolysis 45, 18–26 (2018). https://doi.org/10.1007/s11239-017-1593-y

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  • DOI: https://doi.org/10.1007/s11239-017-1593-y

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