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Risk of Complications After a Peptic Ulcer Diagnosis: Effectiveness of Proton Pump Inhibitors

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Abstract

Background

Few studies have evaluated the prevention of upper gastrointestinal complications (UGIC; bleeding or perforation) in patients with uncomplicated peptic ulcer (PU). We assessed the effect of proton pump inhibitors (PPI) in a non-randomized setting. To maximize exchangeability of exposed and unexposed groups we restricted the study to patients with a new diagnosis of PU, i.e., a clear indication. To minimize selection bias we mimicked an intention to treat approach by assessing the effect of PPI prescription after PU diagnosis.

Methods

Within a population of subjects aged 40–84 years from The Health Improvement Network database, 1997–2006, we identified 3,850 patients with incident PU. Among them, we confirmed 74 first UGIC episodes during a mean follow-up of 4 years. Exposure was prescription coverage during the month following PU diagnosis. We performed a nested case–control analysis and compared UGIC cases with 400 controls matched for age, sex, year and duration of follow-up. Relative risks (RR) and 95 % confidence intervals (CI) were estimated.

Results

The overall incidence of UGIC was 4.6 cases/1,000 person-years; it was highest during the months after PU diagnosis, increased with age, and it was higher in men and subjects with Helicobacter pylori infection, anemia, and alcohol use at PU diagnosis. The RR for UGIC associated with PPI prescriptions during the month after PU diagnosis was 0.56 (95 % CI 0.31–1.0). The RR for NSAIDs with and without a PPI was 1.72 (0.68–4.45) and 3.27 (0.85–12.67), respectively.

Conclusions

Findings suggest that prescription of PPIs after a PU diagnosis is associated with a reduced risk of UGIC.

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Acknowledgments

The Pharmacoepidemiology Program at the Harvard School of Public Health and CEIFE are partially supported by training and research grants from various pharmaceutical companies, some of which manufacture non-steroidal anti-inflammatory drugs and/or gastroprotective agents. This study was funded by an unrestricted research grant from AstraZeneca R&D Mölndal, Sweden.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA

    Sonia Hernández-Díaz

  2. Spanish Center for Pharmacoepidemiological Research, Calle Almirante 28, 2º, Madrid, Spain

    Elisa Martín-Merino & Luis A. García Rodríguez

Authors
  1. Sonia Hernández-Díaz
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  2. Elisa Martín-Merino
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  3. Luis A. García Rodríguez
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Corresponding author

Correspondence to Sonia Hernández-Díaz.

Appendices

Appendix 1

See Fig. 3.

Fig. 3
figure 3

Simplified causal diagram for an observational study with prescription of Z, use of treatment A, and outcome Y. U represents the unmeasured common causes of A and Y. An “intention to treat” analysis of the Z-Y association will be confounded unless prognostic factors L1 are adjusted for. An “as treated” analysis of the A-Y association will be confounded unless all prognostic factors L are adjusted for

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Appendix 2

See Figs. 4, and 5.

Fig. 4
figure 4

Identification of study population

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Fig. 5
figure 5

Summary of subjects included in the cohort of uncomplicated peptic ulcer (PU) and considered cases of upper gastrointestinal complications within this cohort. Estimated accuracy in parenthesis

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Hernández-Díaz, S., Martín-Merino, E. & García Rodríguez, L.A. Risk of Complications After a Peptic Ulcer Diagnosis: Effectiveness of Proton Pump Inhibitors. Dig Dis Sci 58, 1653–1662 (2013). https://doi.org/10.1007/s10620-013-2561-9

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  • DOI: https://doi.org/10.1007/s10620-013-2561-9

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