warfarin and Peptic-Ulcer-Perforation

Traditional nonaspirin, nonsteroidal anti-inflammatory drugs (tNSAIDs) have been associated with a 3- to 5-fold increased risk in upper gastrointestinal complications (UGIC). Whether use of selective inhibitors of cyclooxygenase-2 (COXIBs) will translate into a clinically relevant reduced toxicity has not been widely investigated in the general population.. We conducted a nested case control study using The Health Improvement Network Database identifying 1561 cases of UGIC between January 2000 and 2005. A random sample of 10,000 controls was frequency matched to the cases by age, sex, and calendar year.. The adjusted relative risk (RR) of UGIC associated with current use was 3.7 (95% CI: 3.1-4.3) for tNSAIDs and 2.6 (95% CI: 1.9-3.6) for COXIBs. Daily dose was a predictor of increased risk for both tNSAIDs and COXIBs. Users of tNSAIDs with a prolonged plasma half-life or slow release formulations had an augmented risk of UGIC. Overall, the estimate of RR associated with COXIBs was 0.8 (95% CI: 0.6-1.1) compared with current use of tNSAIDs, and, among nonusers of aspirin, the corresponding estimate of RR associated with COXIBs was 0.6 (95% CI: 0.4-0.9).. COXIBs present a better upper gastrointestinal safety than tNSAIDs, although the risk of UGIC for an individual drug is determined by its daily dose and plasma drug exposure in addition to its selectivity for cyclooxygenase-2. Also, concomitant use of aspirin is a strong effect modifier of COXIBs that negates the superior gastrointestinal safety over tNSAIDs in the absence of aspirin use.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Anticoagulants; Aspirin; Case-Control Studies; Cohort Studies; Cyclooxygenase 2 Inhibitors; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Interactions; Duodenal Ulcer; Gastrointestinal Diseases; Half-Life; Humans; Peptic Ulcer Hemorrhage; Peptic Ulcer Perforation; Retrospective Studies; Risk Assessment; Risk Factors; Steroids; Stomach Ulcer; Time Factors; United Kingdom; Upper Gastrointestinal Tract; Warfarin