Original ResearchFull Report: Clinical—Alimentary TractRisk of Upper Gastrointestinal Bleeding From Different Drug Combinations
Section snippets
Data Sources
Data were obtained from a network of 7 electronic health record (EHR) databases from 3 countries. The EU-ADR Project (Exploring and Understanding Adverse Drug Reactions by integrative mining of clinical records and biomedical knowledge) has successfully established a platform that integrates data from various repositories of European EHRs for evaluation of drug safety.11
We analyzed data from 3 primary care databases (Integrated Primary Care Information [IPCI, The Netherlands]; Health Search/CSD
Risk of UGIB With Drug Monotherapy
In total, 114,835 patients with UGIB (cases) with corresponding follow-up of 930,888 person-years were included in the analysis (Table 1). For all drugs of interest, monotherapy showed a significantly increased relative risk compared with no use of any of the drugs of interest. Monotherapy with nsNSAIDs was associated with an IRRp of 4.3 (95% CI, 4.1–4.4), which is higher than monotherapy with either COX-2 inhibitors (IRRp, 2.9; 95% CI, 2.7–3.2) or low-dose aspirin (IRRp, 3.1; 95% CI, 2.9–3.2) (
Discussion
We determined the magnitude of increased risk of diagnosed UGIB when nsNSAIDs, COX-2 inhibitors, and low-dose aspirin were combined with specific drug classes that may be independently associated with diagnosed UGIB. Although it may seem reasonable to assume synergistic effects with concurrent use of drugs that independently increase risk, these effects have rarely been investigated. To study the risk of diagnosed UGIB during use of specific drug combinations, it is essential to have a large
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This article has an accompanying continuing medical education activity on page e13. Learning Objective: Upon completion of these exercises, successful learners will be able to recognize, differentiate and apply the risk and excess risk of upper gastrointestinal bleeding associated with use of non-steroidal anti-inflammatory drugs and low-dose aspirin combined with other drugs.
Conflicts of interest The authors disclose the following: V.E.V., as an employee of Erasmus University Medical Center, has conducted research for AstraZeneca. M.J.S. has accepted a full-time position at Janssen R&D since completion of this research. R.H. is scientific director of PHARMO Institute, which performs studies for various pharmaceutical companies. G.M. has started working for the European Medicines Agency since completion of this research. M.C.J.M.S is coordinating a research group that has unconditional research grants from Pfizer, Novartis, and Lilly, none of which are related to this research. The remaining authors disclose no conflicts.
Funding EU-ADR is a research and development project funded by the European Commission Seventh Framework Programme (FP7/2007–2013) under grant no. 215847–The EU-ADR Project. The funding agency had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.