The Assessment of Risk for Gastrointestinal Injury with Anticoagulant and Antiplatelet Drugs: The Possible Beneficial Effect of Eicosapentaenoic Acid for the Risk of Gastrointestinal Injury

Abstract

Antithrombotic drugs have been increasingly used for treating ischemic cardiovascular diseases among the elderly in Japan. However, antithrombotic drugs are known to be risk factors for gastrointestinal injury. Therefore, we conducted a pharmacoepidemiologic study on patients receiving antithrombotic drugs to identify the risk factors for gastrointestinal injury. This retrospective case-control study included patients who were prescribed antithrombotic drugs at the Ehime University Hospital between April and September 2010. Of the 3271 patients who received antithrombotic drug therapy, 172 (5.3%) developed gastrointestinal injuries, including gastric ulcers, duodenal ulcers, and hemorrhagic gastrointestinal injuries. Further, the incidence of gastrointestinal injury was higher in patients with hypertension than in those without (p<0.0001). Multivariate adjusted odds ratios and 95% confidence intervals were calculated using stepwise logistic regression. The adjusted odds ratios for gastrointestinal injury were 1.56 (95% confidence interval 1.07-2.36) for hypertension, 1.70 (1.17-2.50) for low-dose aspirin, 2.77 (1.70-4.49) for clopidogrel, 1.95 (1.23-3.08) for warfarin, and 4.13 (2.88-5.95) for nonsteroidal anti-inflammatory drugs. On the other hand, the nonadjusted odds ratio for drug-associated gastrointestinal injury was 0.43 (0.20-0.84) for eicosapentaenoic acid (EPA). In addition, we found that patients aged 70 years or older were at increased risk of drug-associated gastrointestinal injury. These findings suggest that while many antithrombotic drugs are risk factors for gastrointestinal injury, EPA may be a safe option for suppressing or preventing gastrointestinal injury.Key words antithrombotic drug; gastrointestinal injury; eicosapentaenoic acid; nonsteroidal anti-inflammatory drug; elderly patient At present, people older than 65 years account for more than 22% of the entire population in Japan, satisfying the United Nations definition of "ultra-ageing society" (percentage of elderly people, over 21%). Elderly people tend to have multiple comorbidities. Myocardial infarction and cerebral infarction are representative geriatric diseases whose incidence increases with age. In Japan, these ischemic cardiovascular diseases are major causes of death. Cerebral infarction is a disease causing serious problems related to the welfare of people since they are likely to develop sequelae (hemiplegia), making them dependent on the assistance from others during daily life.When the "Guidelines on Anticoagulant and Antiplatelet Drug Therapy for Cardiovascular Diseases" were revised in 2009, the management of gastrointestinal ulcers caused by antiplatelet drugs in clinical practice was added as another important topic.1) This revision was based on the fact that while the onset of peptic ulcers had decreased as a result of Helicobacter pylori eradication therapy, there had been an elevation in the risk of gastrointestinal complications (gastrointestinal ulcers or hemorrhagic gastrointestinal lesions) associated with nons...

Concurrent Use of Low‐Dose Aspirin and Omega‐3 Fatty Acids and Risk of Upper Gastrointestinal Complications: A Cohort Study with Nested Case–Control Analysis

“…Only two prior observational studies investigated the gastrointestinal safety of LDA and OM3 , but differences in outcome and/or exposure definition do not allow direct comparisons with our results. The first study was a retrospective cohort analysis that compared the frequency of bleeding complications in 182 patients exposed to aspirin plus clopidogrel plus OM3 with that observed in the same number of patients taking aspirin plus clopidogrel.…”

“…Moreover, none of the observed events concerned the upper gastrointestinal tract. The second study adopted a retrospective case–control design to investigate the risk of gastrointestinal injuries among patients who were prescribed antithrombotic drugs in a Japanese university hospital. A total of 172 events were observed, of which over 90% concerned the upper gastrointestinal tract.…”

Aspirin Administration Affects Neurochemical Characterization of Substance P-Like Immunoreactive (SP-LI) Nodose Ganglia Neurons Supplying the Porcine Stomach

“…ASA (also known as aspirin) is widely used as antiinflammatory, antipyretic, and analgesic medicine, which causes the inactivation of the cyclooxygenase (COX) enzyme [27]. Apart from therapeutic activity, aspirin also shows side effects which are particularly evident within the stomach, where taking this drug may result in the gastric mucosal injury [28]. It should be underlined that although the mechanisms of aspirin activity have been the subject of many studies [29], knowledge concerning its influence on extrinsic gastrointestinal innervation is extremely scarce [30].…”