Upper gastrointestinal bleeding associated with NSAIDs, other drugs and interactions: a nested case–control study in a new general practice database
To test the ability a new Spanish primary care research database (BIFAP) to capture the association between upper gastrointestinal bleeding (UGIB) and NSAIDs and other drugs and compare the results with previous studies.
We performed a nested case–control study in persons aged 40–90 years old included in the period 2001–2005. Potential cases were selected through a computer search followed by an individual blinded review. Controls matched for age, sex and calendar year were randomly selected. The exposure window was defined as 0–30 days before the index date. Adjusted odds ratios were obtained through unconditional logistic regression models.
In a study cohort of 669,115 subjects (1,576,442 person-years) we retrieved 1,193 valid incident cases. Increased risks were found with current use of NSAIDs (RR = 1.72; 95 %CI: 1.41–2.09), metamizole (1.52; 1.09–2.13), low-dose aspirin (1.74; 1.37–2.21), other antiplatelet drugs (1.73; 1.27–2.36), and oral anticoagulants (2.00; 1.44–2.77). We did not find an increased risk with current use of oral corticosteroids (1.11; 0.66–1.86), SSRIs (1.05; 0.77–1.42), or paracetamol (1.00; 0.82–1.23). Acid-suppressing drugs reduced the risk among users of NSAIDs (0.58; 0.39–0.85), particularly in users with antecedents of peptic ulcer (0.16; 0.05–0.58). We detected a decreasing time-trend in the relative risk and the population attributable proportion associated with NSAIDs over the study period.
The increased risk of UGIB associated with NSAIDs was lower than previously reported, which could partly be explained by methodological differences, but a decreasing burden over time of this drug safety problem is suggested. BIFAP has shown to be a valuable tool for pharmacoepidemiological research.
KeywordsNSAIDs Upper gastrointestinal bleeding Adverse drug reactions Acid-suppressing drugs
- 4.Salvador A, Moreno JC, Sonego D, Garcia-Rodriguez LA, de Abajo FJ (2002) El proyecto BIFAP: Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria. Aten Primaria 30:655–661Google Scholar
- 5.BIFAP, Base de datos para la investigación farmacoeopidemiológica en atención primaria. Available at: http://www.bifap.org
- 6.World Health Organization. International Classification of Primary Care, second edition (ICPC-2). Available at: http://www.who.int/classifications/icd/adaptations/icpc2/en/index.html
- 7.WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD index. Available at: http://www.whocc.no/atc_ddd_index/
- 10.Walker A (1991) Observation and inference—An introduction to the methods of epidemiology. Epidemiology Resources Inc., Newton Lower FallsGoogle Scholar
- 11.Rothman K (1986) Interaction between causes. Modern epidemiology. Little, Brown and Company, Boston, pp 311–326Google Scholar
- 17.Lanas A, García-Rodríguez LA, Arroyo MT, Gomollón F, Feu F, González-Pérez A et al (2006) Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations. Gut 55:1731–1738PubMedCrossRefGoogle Scholar
- 27.Lanas A, García-Rodríguez LA, Arroyo MT, Bujanda L, Gomollón F, Forné M et al (2007) Effect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants. Am J Gastroenterol 102:507–515PubMedCrossRefGoogle Scholar
- 28.Vonkeman HE, Fernandes RW, van der Palen J, van Roon EN, van de Laar MAFJ (2007) Proton-pump inhibitors are associated with a reduced risk for bleeding and perforated gastrodudenal ulcers attributable to non-steroidal anti-inflammatory drugs: a nested case–control study. Arthritis Res Ther 9:R52. doi:10.1186/ar2207 PubMedCrossRefGoogle Scholar