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Acute Middle Gastrointestinal Bleeding Risk Associated with NSAIDs, Antithrombotic Drugs, and PPIs: A Multicenter
Naoyoshi Nagata1, Ryota Niikura2, Atsuo Yamada2
1Departments of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Tokyo, Japan.
Background:
Middle gastrointestinal bleeding (MGIB) risk has not been fully investigated due to its extremely rare occurrence and the need for multiple endoscopies to exclude upper and lower gastrointestinal bleeding. This study investigated whether MGIB is associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin (LDA), thienopyridines, anticoagulants, and proton-pump inhibitors (PPIs), and whether PPI use affects the interactions between MGIB and antithrombotic drugs.
Methods:
In this multicenter, hospital-based, case-control study, 400 patients underwent upper and lower endoscopy, 80 had acute overt MGIB and 320 had no bleeding and were matched for age and sex as controls (1:4). MGIB was additionally evaluated by capsule and/or double-balloon endoscopy, after excluding upper and lower GI bleeding. Adjusted odds ratios (AOR) for MGIB risk were calculated using conditional logistic regression. To estimate the propensity score, we employed a logistic regression model for PPI use.
Results:
In patients with MGIB, mean hemoglobin level was 9.4 g/dL, and 28 patients (35%) received blood transfusions. Factors significantly associated with MGIB were chronic kidney disease (p<0.001), liver cirrhosis (p = 0.034), NSAIDs (p<0.001), thienopyridines (p<0.001), anticoagulants (p = 0.002), and PPIs (p<0.001). After adjusting for these factors, NSAIDs (AOR, 2.5; p = 0.018), thienopyridines (AOR, 3.2; p = 0.015), anticoagulants (AOR, 4.3; p = 0.028), and PPIs (AOR; 2.0; p = 0.021) were independently associated with MGIB. After adjusting for propensity score, the use of PPIs remained an independent risk factors for MGIB (AOR, 1.94; p = 0.034). No significant interactions were observed between PPIs and NSAIDs (AOR, 0.7; p = 0.637), LDA (AOR, 0.3; p = 0.112), thienopyridine (AOR, 0.7, p = 0.671), or anticoagulants (AOR, 0.5; p = 0.545).
Conclusions:
One-third of patients with acute small intestinal bleeding required blood transfusion. NSAIDs, thienopyridines, anticoagulants, and PPIs increased the risk of acute small intestinal bleeding. However, there were no significant interactions found between antithrombotic drugs and PPI use for bleeding risk.
Insights
Non-steroidal anti-inflammatory drugs (NSAIDs), thienopyridines, anticoagulants, and proton-pump inhibitors (PPIs) are linked to middle gastrointestinal bleeding (MGIB). However, PPIs do not significantly alter the bleeding risk associated with antithrombotic drugs.
Area of Science:
- Gastroenterology
- Pharmacology
- Clinical Medicine
Background:
- Middle gastrointestinal bleeding (MGIB) is rare and challenging to diagnose.
- Investigating MGIB risk factors, including medication use, is crucial.
Purpose of the Study:
- To determine the association between MGIB and specific drug classes: NSAIDs, low-dose aspirin (LDA), thienopyridines, anticoagulants, and PPIs.
- To examine if PPI use modifies the interaction between MGIB and antithrombotic drugs.
Main Methods:
- A multicenter, hospital-based case-control study involving 400 patients (80 MGIB cases, 320 controls).
- Diagnosis of MGIB confirmed by endoscopy, capsule endoscopy, and/or double-balloon endoscopy after excluding upper and lower GI bleeding.
- Conditional logistic regression and propensity score analysis were used to calculate adjusted odds ratios (AOR).
Main Results:
- NSAIDs, thienopyridines, anticoagulants, and PPIs were independently associated with increased MGIB risk (AORs ranging from 1.94 to 4.3).
- Proton-pump inhibitor (PPI) use remained an independent risk factor for MGIB after propensity score adjustment (AOR, 1.94).
- No significant interactions were found between PPIs and NSAIDs, LDA, thienopyridines, or anticoagulants regarding bleeding risk.
Conclusions:
- NSAIDs, thienopyridines, anticoagulants, and PPIs are significant risk factors for acute small intestinal bleeding.
- Proton-pump inhibitors do not appear to potentiate the bleeding risk when used concurrently with antithrombotic agents.
