Time-Trends in Use of Gastroprotective Strategies With NSAID Treatment in the United Kingdom, Italy, and the Netherlands; A Comparative Study

Background: To reduce the risk of upper gastrointestinal (UGI) complications related to non-steroidal anti-inflammatory drugs (NSAIDs), gastroprotective strategies (GPS) are recommended in patients at risk. Aim: To compare GPS prescription behaviour by general practitioners (GP) in 3 European countries. Methods: We conducted a population-based cohort study in 3 GP databases: 1) United Kingdom's (UK) GP Research Database (1998-2008), 2) Italy's (IT) Health Search/Thales Database (2000-2007), and 3) the Dutch (NL) Integrated Primary Care Information database (1996-2006). Study cohorts comprised all incident NSAID users ≥50 yrs. As preventive strategies we considered: 1) co-prescription of proton pump inhibitors, double dose H2-receptor antagonists, or misoprostol, or 2) use of a cyclooxygenase- 2-specific inhibitor (coxib). Consistent with American College of Gastroenterology treatment guidelines, appropriate prescription was defined as the use of a GPS in NSAID users with ≥1 UGI risk factor (history of UGI bleeding/ulceration, age ≥ 65 yrs, concomitant use of anticoagulants, aspirin, or corticosteroids) and also no GPS in patients without UGI risk factors. Under-prescription was defined as no GPS in patients with ≥1 UGI risk factor. Over-prescription was the presence of a GPS in patients with no UGI risk factors. Results: The study populations comprised of 384,649 UK (mean age: 64.8 yrs, 41% male), 179,030 IT (mean age: 64.6 yrs, 41.7% male) and 55,005 NL NSAID users (mean age: 63.4 yrs, 42.6% male). In the UK, appropriate prescription increased from 51% in 1998 to 59% in 2008 (linear trend (lt) p<0.001) and over-prescription from 3% to 7% (lt p=0.04). Underprescription fell from 46% to 34% (lt p<0.001). In IT, appropriate prescription rose from 46% in 2000 to 60% in 2007 (lt p<0.001) and over-prescription from 3% to 8% (lt p= 0.74), while under-prescription fell from 51% to 32% (lt p=0.01). In the NL, appropriate prescription rose from 53% in 1996 to 63% in 2006 (lt p<0.001) and over-prescription from 4% to 14% (lt p<0.001). Under-prescription decreased from 43% to 23% (lt p<0.001). Between 2000 and 2006, appropriate prescription was significantly higher and underprescription significantly lower in NL compared to UK and IT (p<0.001). Conclusions: The appropriate prescription of GPS has increased over the past years in all three countries assessed. Although under-prescription of GPS use has decreased, it still occurred in 23-34% of NSAID users with upper GI risk factors. This still requires major improvement. The variability across countries was smaller than expected, considering the cultural and structural differences between national health care systems. However, differences across countries are likely to influence the incidence of NSAID-related UGI complications and health care costs.