Suboptimal gastroprotective coverage of NSAID use and the risk of upper gastrointestinal bleeding and ulcers: an observational study using three European databases

Gut. 2011 Dec;60(12):1650-9. doi: 10.1136/gut.2011.239848. Epub 2011 Jun 2.


Background: Gastro-protective agents (GPA) are co-prescribed with non-steroidal anti-inflammatory drugs (NSAID) to lower the risk of upper gastrointestinal (UGI) events. It is unknown to what extent the protective effect is influenced by therapy adherence.

Aim: To study the association between GPA adherence and UGI events among non-selective (ns) NSAID users.

Methods: The General Practice Research Database (UK 1998-2008), the Integrated Primary Care Information database (the Netherlands 1996-2007) and the Health Search/CSD Longitudinal Patient Database (Italy 2000-2007) were used. A nested case-control design was employed within a cohort of nsNSAID users aged ≥50 years, who also used a GPA. UGI event cases (UGI bleeding and/or symptomatic ulcer with/without obstruction/perforation) were matched to event-free members of the cohort for age, sex, database and calendar time. Adherence to GPA was calculated as the proportion of nsNSAID treatment days covered by a GPA prescription. Adjusted OR with 95% CI were calculated.

Results: The cohort consisted of 618 684 NSAID users, generating 1 107 266 nsNSAID episodes. Of these, 117 307 (10.6%) were (partly) covered by GPA, 4.9% of which with a GPA coverage <20% (non-adherence), and 68.1% with a GPA coverage >80% (full adherence). 339 patients experienced an event. Among non-adherers, the OR was 2.39 (95% CI 1.66 to 3.44) for all UGI events and 1.89 (95% CI 1.09 to 3.28) for UGI bleeding alone, compared to full adherers.

Conclusions: The risk of UGI events was significantly higher in nsNSAID users with GPA non-adherence. This underlines the importance of strategies to improve GPA adherence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Ulcer Agents / therapeutic use
  • Case-Control Studies
  • Cohort Studies
  • Databases, Factual* / statistics & numerical data
  • Female
  • Gastrointestinal Hemorrhage / chemically induced*
  • Gastrointestinal Hemorrhage / epidemiology
  • Gastrointestinal Hemorrhage / prevention & control
  • Guideline Adherence / statistics & numerical data
  • Humans
  • Incidence
  • Italy / epidemiology
  • Logistic Models
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Poisson Distribution
  • Practice Patterns, Physicians' / standards
  • Practice Patterns, Physicians' / statistics & numerical data
  • Risk Factors
  • Stomach Ulcer / chemically induced*
  • Stomach Ulcer / epidemiology
  • Stomach Ulcer / prevention & control
  • United Kingdom / epidemiology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Anti-Ulcer Agents