Incidence Of Upper Gastrointestinal Events Research Articles

What is the harm-benefit ratio of Cox-2 inhibitors?

Selective cyclooxygenase-2 (Cox-2) inhibitors, developed to reduce the risk of NSAID-related gastrointestinal (GI) complications, have been associated with an increased risk of cardiovascular events. Our objective was to determine the balance of potential harm and benefit related to Cox-2 inhibitors' exposure. The study population included patients aged 40+ years who received a prescription for Cox-2 inhibitors and were included in the General Practice Research Database. The incidence of upper GI events, myocardial infarction (MI) and stroke was estimated in this cohort. It was assumed that patients had experienced the upper GI and cardiovascular effects, as observed in clinical trials [relative rate (RR) of 0.49 for upper GI and 1.86 for MI]. Simulation methodology was used to estimate attributable risks, i.e. the difference between exposed and unexposed event probabilities. The study population included 155,439 Cox-2 users. The number of upper GI events prevented by Cox-2 inhibitors was 179, while the number of excess MI cases was 83 per 10,000 patients treated for 4 years. A strong association was found between extent of GI benefit and cardiovascular harm. There was a large difference in the frequency of benefit over harm in only 6% of the patients (difference of 1% or more); 23% of the patients had more harm than benefit, including those with a history of ischaemic heart disease. The benefit of Cox-2 inhibitors in reducing the frequency of upper GI events may be offset by their cardiovascular harm, particularly in patients with risk factors for cardiovascular disease.

Upper Gastrointestinal Adverse Events and Cyclical Etidronate

PURPOSE: Recently, there have been several published case reports of esophagitis associated with the use of aminobisphosphonates. The objective of this study was to evaluate the upper gastrointestinal (GI) safety of cyclical etidronate, an alkylbisphosphonate, in routine clinical practice.PATIENTS AND METHODS: Information was obtained from 550 general practices in the United Kingdom that provide the medical records to the General Practice Research Database. A group of 7977 cyclical etidronate takers and 2 age-, gender-, and practice-matched control groups (1 with osteoporosis and 1 without) were analyzed.RESULTS: For cyclical etidronate takers, the average age was 71.6 years and total follow-up was 10,328 person-years. The risk of upper GI events (inflammation or ulcer of esophagus, stomach, or duodenum) was comparable between patients taking etidronate and the two control groups. The adjusted relative risk of upper GI events was 0.92 (95% confidence interval [CI] 0.78 to 1.09) for etidronate takers compared with osteoporosis controls and 1.12 (CI 0.91 to 1.37) compared to nonosteoporosis controls. For esophagitis and esophageal ulcers, the relative risks were 0.83 (CI 0.64 to 1.08) and 0.97 (CI 0.71 to 1.31) respectively. The incidence of upper GI events during nonsteroidal anti-inflammatory drug (NSAID), aspirin, or corticosteroid use was similar across the three groups. The upper GI risks of etidronate NSAID users were 0.71 (CI 0.45 to 1.11) and 2.06 (CI 0.98 to 4.35) compared with NSAID users in the two control groups.CONCLUSIONS: These results support the GI tolerability and safety profile of cyclical etidronate in routine clinical practice. Concomitant use of cyclical etidronate with NSAIDs, aspirin, or corticosteroids did not increase the incidence of upper GI events.