Aim: To investigate prescribing pattern in low-dose aspirin users and physician awareness of preventing aspirin-induced gastrointestinal (GI) injury with combined protective medications.
Methods: A retrospective drug utilization study was conducted in the 2nd Affiliated Hospital, School of Medicine, Zhejiang University. The hospital has 2300 beds and 2.5 million outpatient visits annually. Data mining was performed on all aspirin prescriptions for outpatients and emergency patients admitted in 2011. Concomitant use of proton-pump inhibitors (PPIs), histamine 2-receptor antagonists (H2RA) and mucoprotective drugs (MPs) were analyzed. A defined daily dose (DDD) methodology was applied to each MP. A further investigation was performed in aspirin users on combination use of GI injurious medicines [non-steoid anti-inflammatory drugs (NSAIDs), corticosteroids and clopidogrel and warfarin] or intestinal protective drugs (misoprostol, rebamipide, teprenone and gefarnate). Data of major bleeding episodes were derived from medical records and adverse drug reaction monitoring records. The annual incidence of major GI bleeding due to low-dose aspirin was estimated for outpatients.
Results: Prescriptions for aspirin users receiving PPIs, H2RA and MPs (n = 1039) accounted for only 3.46% of total aspirin prescriptions (n = 30 015). The ratios of coadministration of aspirin/PPI, aspirin/H2RA, aspirin/MP and aspirin/PPI/MP to the total aspirin prescriptions were 2.82%, 0.12%, 0.40% and 0.12%, respectively. No statistically significant difference was observed in age between patients not receiving any GI protective medications and patients receiving PPIs, H2RA or MPs. The combined medication of aspirin and PPI was used more frequently than that of aspirin and MPs (2.82% vs 0.40%, P < 0.05) and aspirin/H2RA (2.82% vs 0.12%, P < 0.05). The values of DDDs of MPs in descending order were as follows: gefarnate, hydrotalcite > teprenone > sucralfate oral suspension > L-glutamine and sodium gualenate granules > rebamipide > sucralfate chewable tablets. The ratio of MP plus aspirin prescriptions to the total MP prescriptions was as follows: rebamipide (0.47%), teprenone (0.91%), L-glutamine and sodium gualenate granules (0.92%), gefarnate (0.31%), hydrotalcite (1.00%) and sucralfate oral suspension (0.13%). Percentages of prescriptions containing aspirin and intestinal protective drugs among the total aspirin prescriptions were: rebamipide (0.010%), PPI/rebamipide (0.027%), teprenone (0.11%), PPI/teprenone (0.037%), gefarnate (0.017%), and PPI/gefarnate (0.013%). No prescriptions were found containing coadministration of aspirin and other NSAIDs. Among the 3196 prescriptions containing aspirin/clopidogrel, 3088 (96.6%) prescriptions did not contain any GI protective medicines. Of the 389 prescriptions containing aspirin/corticosteroids, 236 (60.7%) contained no GI protective medicines. None of the prescriptions using aspirin/warfarin (n = 22) contained GI protective medicines. Thirty-five patients were admitted to this hospital in 2011 because of acute hemorrhage of upper digestive tract induced by low-dose aspirin. The annual incidence rates of major GI bleeding were estimated at 0.25% for outpatients taking aspirin and 0.5% for outpatients taking aspirin/warfarin, respectively.
Conclusion: The prescribing pattern of low-dose aspirin revealed a poor awareness of preventing GI injury with combined protective medications. Actions should be taken to address this issue.
Keywords: Combined medications; Defined daily dose; Drug utilization; Gastrointestinal injury; Histamine 2-receptor antagonists; Low-dose aspirin; Mucoprotective drugs; Prescribing patterns; Proton-pump inhibitors; Small bowel injury.