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Cardiovascular and gastrointestinal events of three antiplatelet therapies: clopidogrel, clopidogrel plus proton-pump inhibitors, and aspirin plus proton-pump inhibitors in patients with previous gastrointestinal bleeding

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Abstract

Background

Concomitant use of antiplatelet agents and proton-pump inhibitors (PPIs) has been recommended in patients with a history of gastrointestinal (GI) hemorrhage. However, recent studies have reported that PPIs may alter clopidogrel’s pharmacokinetics and potentially lead to an increased risk of recurrent adverse cardiovascular (CV) events.

Methods

Using Taiwan’s 2000–2006 National Health Insurance database, this population-based retrospective cohort study assessed CV and GI events in patients who had a prior history of GI bleeding and had been prescribed ongoing antiplatelet therapy after acute coronary syndrome (ACS) discharge. We identified 3,580 ACS patients and categorized them into (1) those taking clopidogrel alone, (2) those taking clopidogrel plus PPIs, and (3) those taking aspirin plus PPIs. Cox proportional hazards models were used to assess the association between the use of antiplatelet therapies and CV/GI events.

Results

The clopidogrel only group and the clopidogrel plus PPI group were found to be at lower risk for GI events than the aspirin plus PPI group [adjusted hazard ratio (HR) 0.23 (95% confidence interval; CI 0.14–0.36) and HR 0.70 (0.52–0.96), respectively]. However, while the clopidogrel only group had a lower risk of CV events than the aspirin plus PPI group [HR 0.57 (0.38–0.84)], the clopidogrel plus PPI group had a significantly higher CV risk than the aspirin plus PPI group [HR 1.59 (1.18–2.13)].

Conclusions

Our findings suggest that although the use of clopidogrel plus PPIs provides GI benefits, with this treatment, there is an increased CV risk among patients with a history of GI bleeding.

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Acknowledgments

The authors thank the Taiwanese Bureau of National Health Insurance and the National Health Research Institutes for use of the NHI database. The content of this article does not represent the official position of either organization, and the authors bear all responsibility for the results and their interpretation. We thank Dr. C. Daniel Mullins of the University of Maryland for providing consultation and assistance with the revised manuscript. The authors also thank James Steed of National University of Kaohsiung, Taiwan, for editing assistance.

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Author notes

  1. Fei-Yuan Hsiao

    Present address: Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, 1 Jen-Ai Road, Section 1, Taipei, 10051, Taiwan

Authors and Affiliations

  1. Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan

    Yi-Wen Tsai & Ken N. Kuo

  2. Institute of Health and Welfare Policy, National Yang-Ming University, Taipei, Taiwan

    Yi-Wen Tsai & Weng-Foung Huang

  3. Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Tao-Yuan, Taiwan

    Yu-Wen Wen

  4. Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Miaoli, Taiwan

    Pei-Fen Chen

  5. Pharmaceutical Health Services Research Department, University of Maryland School of Pharmacy, 220 Arch Street, 12th Floor, Baltimore, MD, 21201, USA

    Fei-Yuan Hsiao

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  1. Yi-Wen Tsai
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Correspondence to Fei-Yuan Hsiao.

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Tsai, YW., Wen, YW., Huang, WF. et al. Cardiovascular and gastrointestinal events of three antiplatelet therapies: clopidogrel, clopidogrel plus proton-pump inhibitors, and aspirin plus proton-pump inhibitors in patients with previous gastrointestinal bleeding. J Gastroenterol 46, 39–45 (2011). https://doi.org/10.1007/s00535-010-0299-0

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  • DOI: https://doi.org/10.1007/s00535-010-0299-0

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