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Suboptimal gastroprotective coverage of NSAID use and the risk of upper gastrointestinal bleeding and ulcers: an observational study using three European databases
  1. Eva M van Soest1,
  2. Vera E Valkhoff1,2,
  3. Giampiero Mazzaglia3,
  4. René Schade1,
  5. Mariam Molokhia4,
  6. Jay L Goldstein5,
  7. Sonia Hernández-Díaz6,
  8. Gianluca Trifirò1,
  9. Jeanne P Dieleman1,
  10. Ernst J Kuipers2,7,
  11. Miriam C J M Sturkenboom1,8
  1. 1Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands
  2. 2Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
  3. 3Health Search, Italian College of General Practitioners, Florence, Italy
  4. 4Department of Primary Care and Population Health Sciences, Kings College, London, UK
  5. 5Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA
  6. 6Department of Epidemiology, Harvard School of Public Health, Boston, USA
  7. 7Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
  8. 8Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands
  1. Correspondence to Professor Miriam Sturkenboom, Department of Medical Informatics, Erasmus University Medical Center, Postbus 2040, Rotterdam 3000 CA, The Netherlands; m.sturkenboom{at}


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.

  • Anti-ulcer agents
  • bleeding peptic ulcer
  • gastric and duodenal ulcers
  • multi-database study
  • non-steroidal anti-inflammatory agents
  • peptic ulcer
  • peptic ulcer haemorrhage
  • proton pump inhibitors

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  • Funding This study has been funded by AstraZeneca Plc under contractual conditions with Erasmus University that ensure freedom of publication. The study was designed and conducted independently of AstraZeneca.

  • Correction notice This article has been corrected since it was published Online First. In figure 1, ‘360430’ has been corrected to ‘36 430’ and in table 3, ‘4522’ has been corrected to '46 522'.

  • Competing interests MCJMS is head of a unit that occasionally conducts research for pharmaceutical companies. She has been consultant for Pfizer and Lundbeck in the recent past on issues not related to this study. MM has received grants from the SAEC consortium (collaboration of academia and industry), and from AstraZeneca and Pfizer. SHD works at the Pharmacoepidemiology Program at the Harvard School of Public Health which is partly supported by training grants from Pfizer, Novartis and Wyeth. She has consulted for pharmaceutical companies, some of which manufacture drugs discussed in this paper. JLG has received research and/or educational funding, consulting fees, contract payments and speaker's honoraria from AstraZeneca, Given, Horizon, Logical Therapeutics, Novartis, Pfizer, POZEN, Takeda and TAP. He has received consulting fees from Amgen, Astellas, GlaxoSmithKline, Merck, Novartis, PLX, Procter & Gamble and Wyeth. Grants have been awarded from Amgen, Novartis and GlaxoSmithKline and contract payments from Amgen and GlaxoSmithKline. EJK has served as a speaker and advisory board member for AstraZeneca. EMvS, VEV, GM, RS, GT and JPD declare no conflicts of interest.

  • Ethics approval This study was conducted with the approval of the scientific and ethical advisory board of each database.

  • Provenance and peer review Not commissioned; externally peer reviewed.