Acute Middle Gastrointestinal Bleeding Risk Associated with NSAIDs, Antithrombotic Drugs, and PPIs: A Multicenter Case-Control Study.

Naoyoshi Nagata,Yoshihiro Hirata,Kazuhiko Koike,Keiji Ogura,Yuka Kobayashi,Makoto Okamoto,Kazuma Fujimoto,Takuro Shimbo,Ryota Niikura,Junichi Akiyama,Toshiyuki Sakurai,Atsuo Yamada,Yuzo Mitsuno,Naomi Uemura,Vince Grolmusz

doi:10.1371/journal.pone.0151332

Abstract

BackgroundMiddle 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.MethodsIn 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.ResultsIn 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).ConclusionsOne-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.

Highlights

Gastrointestinal (GI) bleeding is classified into the three categories of upper GI bleeding (UGIB), middle GI bleeding (MGIB), and lower GI bleeding (LGIB)
Factors significantly associated with Middle gastrointestinal bleeding (MGIB) were chronic kidney disease (p
NSAIDs, thienopyridines, anticoagulants, and PPIs increased the risk of acute small intestinal bleeding

Summary

Introduction

Gastrointestinal (GI) bleeding is classified into the three categories of upper GI bleeding (UGIB), middle GI bleeding (MGIB), and lower GI bleeding (LGIB). Non-steroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin (LDA), thienopyridines, and anticoagulants are known to induce UGIB[3] and LGIB[4,5]. These drugs have the potential to cause mucosal injury in the small intestine[6,7,8,9,10,11], their effect has not been fully investigated on the serious adverse GI event of acute overt MGIB. 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

Results

Conclusion