Original Article

Digestive Diseases and Sciences

, Volume 58, Issue 6, pp 1653-1662

First online:

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

  • Sonia Hernández-DíazAffiliated withDepartment of Epidemiology, Harvard School of Public Health Email author 
  • , Elisa Martín-MerinoAffiliated withSpanish Center for Pharmacoepidemiological Research
  • , Luis A. García RodríguezAffiliated withSpanish Center for Pharmacoepidemiological Research

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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.


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.


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.


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


Peptic ulcer Gastrointestinal complications Proton pump inhibitors Non-steroidal anti-inflammatory drugs Gastroprotection