Non-steroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, non-aspirin antiplatelet drugs and antithrombotic drugs are commonly used in the treatment of arthritis and cardiovascular diseases. As one of the anti-thrombotic drugs, it is well known that NSAIDs can cause upper gastrointestinal tract injury, but studies related to their toxic effects on the lower gastrointestinal tract, especially in causing bleeding, are scarce. However, dual antiplatelet therapy, such as combined low-dose aspirin and thienopyridine derivatives or combined low-dose aspirin and non-thiopyridine drugs, is currently in clinical trials due to therapeutic needs. Moreover, the use of combined NSAID and antiplatelet drug regimens will increase, especially in the elderly population. However, the risk of GI bleeding from such regimens is currently lacking corresponding research data, and the effect on the lower GI tract in particular is currently unknown. Unlike upper GI bleeding, which can be treated with acid suppressants, there are no effective treatment options to prevent lower GI bleeding. Therefore, it is particularly important to identify potential risk factors to infer the likely location of bleeding for treatment. Even in the absence of active bleeding, colonoscopy can be used to diagnose all sites of bleeding of colonic and rectal origin. However, there is still a significant lack of large-scale studies on the correlation between specific drugs and lower GI bleeding events diagnosed by colonoscopy. In Japan, due to the high incidence of colorectal and gastric cancer, upper gastrointestinal endoscopy as well as colonoscopy is performed as soon as a patient presents with GI bleeding to rule out the possibility of early tumor presence. Even in healthy people without any symptoms, upper gastrointestinal endoscopy and colonoscopy are performed as health screening. Therefore, a large number of cases and control cases can be provided for relevant studies. Based on this convenience, a prospective study was conducted by Naoyoshi Nagata’s team at the Department of Gastroenterology and Hepatology, Institute of Clinical Information, National Center for Global Health, Tokyo, Japan. In that study, the authors evaluated the correlation between the use of various antithrombotic drugs and the occurrence of lower gastrointestinal bleeding. Lower gastrointestinal bleeding was diagnosed using colonoscopy as the first-line examination modality, and upper gastrointestinal bleeding was excluded by upper gastrointestinal endoscopy. The aim of this study was to clarify the effect of nonselective or selective nonsteroidal anti-inflammatory drugs, low-dose aspirin, thienopyridine, and other antiplatelet drugs on lower gastrointestinal bleeding. And to compare whether the combined application of antithrombotic drugs has a greater effect on lower GI injury than one antithrombotic drug alone. The results were published in the June 2014 issue of Gastrointestinal Endoscopy. The authors included in the study 319 patients admitted to the hospital on an emergency basis for acute, persistent or recurrent lower GI bleeding and 3358 patients whose bleeding was not detected by colonoscopy. The primary study outcome was assessed as: risk ratios (ORs) for lower GI bleeding with exposure to antithrombotic drugs corrected for age, sex, whether or not they smoked, whether or not they drank alcohol, medication history, comorbidities, and GI symptom scores. Patients were divided into two groups for analysis based on medication use: one antithrombotic drug alone and the combination of antithrombotic drugs, with non-selective NSAIDs or cyclooxygenase 2 inhibitors alone being an independent factor affecting lower GI bleeding. The results showed that the combination of NSAIDs and low-dose aspirin (OR 4.3) or NSAIDs combined with other antiplatelet agents (OR 4.9) was more strongly associated with lower GI bleeding compared with NSAIDs alone (OR 2.3). However, low-dose aspirin, thienopyridine, or other antiplatelet agents alone were not significantly associated with the occurrence of lower gastrointestinal bleeding. However, combined application of low-dose aspirin and thienopyridine (OR 2.2) or low-dose aspirin combined with other antiplatelet agents (OR 3.6) was associated with lower gastrointestinal bleeding. Moreover, the combination of different NSAIDs (OR 4.9) was associated with a higher risk of causing lower GI bleeding compared with one NSAID alone (OR 2.3). The limitation of this study is that it was a single-center study. From this, it is concluded that the use of non-selective or selective NSAIDs alone is associated with the development of lower GI bleeding. Although antiplatelet agents alone were not significantly associated with the development of lower GI bleeding, the combination of NSAIDs and antiplatelet agents or low-dose aspirin in combination with thienopyridine or low-dose aspirin in combination with non-thiopyridine antiplatelet agents were independent risk factors for lower GI bleeding.