Adherence to gastroprotection during cyclooxygenase 2 inhibitor treatment and the risk of upper gastrointestinal tract events: A population-based study

Authors

  • Vera E. Valkhoff,

    Corresponding author
    1. Erasmus University Medical Centre, Rotterdam, The Netherlands
    • Department of Medical Informatics, Erasmus University Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands
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  • Eva M. van Soest,

    1. Erasmus University Medical Centre, Rotterdam, The Netherlands
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  • Giampiero Mazzaglia,

    1. Health Search, Research Institute of the Italian College of General Practitioners, Florence, Italy
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  • Mariam Molokhia,

    1. Kings College London, London, UK
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    • Dr. Molokhia has received consulting fees from the International Serious Adverse Event Consortium (a collaboration of academia and industry) and from AstraZeneca and Pfizer (less than $10,000 each).

  • René Schade,

    1. Erasmus University Medical Centre, Rotterdam, The Netherlands
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  • Gianluca Trifiro,

    1. Erasmus University Medical Centre, Rotterdam, The Netherlands
    2. University of Mesina, Mesina, Italy
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  • Jay L. Goldstein,

    1. University of Illinois at Chicago
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    • Dr. Goldstein has received consulting fees, speaking fees, and/or honoraria from Procter & Gamble, Horizon, TAP/Takeda, Amgen, Astellas, Given, GlaxoSmithKline, Merck, Novartis, PLx, and Wyeth (less than $10,000 each) and from AstraZeneca, Logical Therapeutics, Pfizer, and POZEN (more than $10,000 each).

  • Sonia Hernandez-Diaz,

    1. Harvard School of Public Health, Boston, Massachusetts
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    • Dr. Hernandez-Diaz has received consulting fees from AstraZeneca, Novartis, and GlaxoSmithKline (less than $10,000 each).

  • Ernst J. Kuipers,

    1. Erasmus University Medical Centre, Rotterdam, The Netherlands
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    • Dr. Kuipers has received speaking fees and honoraria for advisory board service from AstraZeneca (less than $10,000 each).

  • Miriam C. J. M. Sturkenboom

    1. Erasmus University Medical Centre, Rotterdam, The Netherlands
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  • Study results were presented in part by Drs. Valkhoff and Sturkenboom at the 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management of the International Society of Pharmacoepidemiology, Brighton, UK, August 2010, and at Digestive Disease Week, Chicago, IL, May 2011.

Abstract

Objective

Guidelines recommend coprescription of gastroprotective agents (GPAs) in patients receiving cyclooxygenase 2 inhibitors (coxibs) who are at high risk of upper gastrointestinal (UGI) tract complications (i.e., patients with a previous complicated ulcer or with multiple risk factors). Suboptimal GPA adherence has been shown to diminish the gastroprotective effect during use of nonselective nonsteroidal antiinflammatory drugs, but little is known about the effect of GPA adherence during coxib treatment. We undertook this study to determine the association between GPA adherence and UGI tract events among patients receiving coxibs.

Methods

Using primary care data from 3 databases, we conducted a case–control study in a cohort of patients age ≥50 years who were newly starting treatment with coxibs and concomitantly taking GPAs. Patients who had a UGI tract event (bleeding or symptomatic ulcer) were matched to event-free controls for age, sex, database, and calendar date. Coxib treatment intervals were defined as consecutive coxib prescriptions with intervening gaps not exceeding the duration of the previous coxib prescription. Adherence to GPAs was calculated as the proportion of days of coxib treatment covered by a GPA prescription. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated using conditional logistic regression analysis.

Results

The coxib plus GPA–treated cohort consisted of 14,416 coxib-treated patients who received GPAs for at least 1 day, yielding 16,442 coxib treatment intervals in which a GPA was coprescribed. Most patients were treated with coxibs for <30 days. Seventy-four patients had a UGI tract event during or shortly after a coxib treatment interval in which a GPA was coprescribed, with an incidence rate of 11.9 (95% CI 9.4–14.8) per 1,000 years of coxib treatment. The risk of UGI tract events was 1.97 (95% CI 0.84–4.60) for patients with <20% adherence to GPAs compared to patients with >80% adherence to GPAs. For every 10% decrease in GPA adherence, the risk of UGI tract events increased by 9% (OR 1.09 [95% CI 1.00–1.18]).

Conclusion

Decreasing GPA adherence among coxib-treated patients is associated with an increased risk of UGI tract events.

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