title: Suboptimal gastroprotective coverage of NSAID use and the risk of upper gastrointestinal bleeding and ulcers: an observational study using three European databases.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Eva M
authors.initials: EM
authors.lastname: van Soest
authors.forename: Vera E
authors.initials: VE
authors.lastname: Valkhoff
authors.forename: Giampiero
authors.initials: G
authors.lastname: Mazzaglia
authors.forename: René
authors.initials: R
authors.lastname: Schade
authors.forename: Mariam
authors.initials: M
authors.lastname: Molokhia
authors.forename: Jay L
authors.initials: JL
authors.lastname: Goldstein
authors.forename: Sonia
authors.initials: S
authors.lastname: Hernández-Díaz
authors.forename: Gianluca
authors.initials: G
authors.lastname: Trifirò
authors.forename: Jeanne P
authors.initials: JP
authors.lastname: Dieleman
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: Miriam C J M
authors.initials: MC
authors.lastname: Sturkenboom
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D015331:Cohort Studies; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control; D019983:Guideline Adherence / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016012:Poisson Distribution; D010818:Practice Patterns, Physicians' / Q000592:standards / Q000706:statistics & numerical data; D012307:Risk Factors; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents