Nonsteroidal Anti-inflammatory Drugs and Upper Gastrointestinal Bleeding, Identifying High-Risk Groups by Excess Risk Estimates

Abstract

Background: The relationship between use of nonsteroidal anti-inflammatory drugs (NSAID) and severe upper gastrointestinal bleeding (UGB) has been established beyond reasonable doubt. The literature on risk factors has almost exclusively focused on comparisons of relative risks in subgroups of patients: men versus women, old versus young and so forth. However, from a pragmatic, clinical viewpoint, only the excess risk provides a meaningful, robust measure of the magnitude of risk factors. The purpose of the study was to determine the excess risks in subgroups of patients and to characterize the utilization pattern of NSAIDs. Methods: A registry-based cohort study was conducted in a prescription and diagnosis registry in Odense, which covered a population of 207,000 persons for a period of 19 months. Results: In total, 183 (113 men and 70 women) UGB patients were identified, of whom 37 were current users of NSAIDs. The standardized incidence rate of UGB was 46 per 100,000 person-years for nonexposed and 253 per 100,000 person-years for exposed person-time, yielding an excess risk of 207 per 100,000 person-years (confidence interval (CI), 132-319) and a standardized incidence ratio (SIR) of 5.5 (CI, 3.9-7.9). Men had a higher excess risk than women (277 versus 150 per 100,000 person-years). The SIR decreased with increasing duration of exposure. The excess risk was particularly high in persons aged 75 years or more (1258 per 100,000 person-years) and in patients with a history of peptic ulcer (879 per 100,000 person-years), being about 10- and 5-fold higher than in the complementary groups. NSAID utilization was remarkably sporadic. We found 31,503 users and a median purchase of 20 defined daily doses. Short-term use was highly prevalent in all age groups. Women, the elderly, and persons with a history of ulcer had a higher prevalence of NSAID use than others. Conclusions: A history of peptic ulcer is associated with adverse outcome of NSAID therapy and should be regarded as a relative contraindication. A similarly strong effect of high age was shown. Male sex and short-term use are minor risk factors. The incidence of NSAID-related UGB can probably be reduced without affecting the overall utilization of NSAIDs.

Key Words:

• Cohort study
• excess risk
• nonsteroidal anti-inflammatory drugs
• peptic ulcer
• risk factor
• upper gastrointestinal bleeding
• utilization