gastrointestinal toxicity induced by non - steroidal anti - inflammatory drugs ( nsaids ) is one of the major causes of peptic ulcers . due to its widespread use
, low - dose aspirin ( lda ) , which is used for prophylaxis of atherothrombotic diseases , plays an important role in the occurrence of peptic ulcers . in japan ,
previous studies have shown that upper gastrointestinal bleeding caused by lda can be decreased with acid suppressants , such as proton pump inhibitors ( ppi ) .
unfortunately , these protective effects are incomplete , and new therapeutic options have not been developed [ 14 ] .
many gastroduodenal mucoprotective drugs have not been evaluated in terms of efficacy for lda - related toxicity , although they are often used in clinical settings in japan .
in addition , there is little clinical information and the current condition of lda - related gastrointestinal mucosal injury remains uncertain in japanese subjects [ 5 , 6 ] .
we conducted this study to clarify the current condition of mucosal injury in japanese patients taking lda and to identify potential effective treatments against lda - induced mucosal injury .
this study involved a retrospective review of medical records . from january 2005 through december 2006 , 5555 patients underwent upper gastrointestinal endoscopy at the department of internal medicine of teikyo university hospital ( tokyo , japan ) . among these patients ,
548 had taken lda for 1 month or more and were selected for inclusion in this study .
patients with malignant diseases , hemorrhage from variceal lesions , and mallory - weiss syndrome were excluded because of difficulty in performing accurate endoscopic evaluations .
two well - trained examiners with more than 10 years experience retrospectively evaluated endoscopic records to determine whether gastroduodenal mucosal injury and bleeding from the lesion were present ; examiners were blinded to patient data .
if the two examiners differed in opinion , another examiner evaluated the record again to make a final diagnosis .
bleeding was diagnosed on the basis of endoscopic evidence of current or recent hemorrhage with drop of hemoglobin of 2  g / dl or more , which was judged to require hospitalization .
minor hemorrhages judged to be treatable on an outpatient basis , such as small clots attached to the gastric wall , were not classified as  bleeding  in the present study .
mucosal injury was defined as obvious findings of gastroduodenal mucosal defects including both erosion ( less than 5  mm in diameter ) and ulcer ( more than 5  mm ) .
background characteristics of the subjects ( age , gender , underlying disease , reason for undergoing examination , past history of gastroduodenal ulcer , and concomitant administration of warfarin , nsaids , ppi , histamine 2-receptor antagonists ( h2ra ) , or other gastric mucoprotective ( mp ) agents ) were ascertained from medical records .
the presence of serum anti - helicobacter pylori ( h. pylori ) antibody was tested using a commercially available kit ( e - plate , eiken chemical co. , tokyo , japan ) in participants who gave written informed consent .
chart review was performed to confirm the present status of the infection in subjects that underwent past eradication treatment .
unadjusted odds ratios ( or ) and 95% confidence intervals ( ci ) were calculated to clarify the significance of differences between two groups , if appropriate .
prior to the study , the protocol was approved by the institutional review board of teikyo university .
underlying diseases of subjects included ischemic heart disease ( 66% ) , cerebrovascular disease ( 30% ) , and systemic arteriosclerosis ( 8% ) .
the influence of background characteristics on gastroduodenal bleeding and mucosal injury are shown in tables  1 and 2 .
the only factor significantly associated with reduced bleeding was co - administration of a ppi . in terms of mucosal injury ,
use of a ppi decreased the prevalence of mucosal injury , whereas the presence of h. pylori increased the prevalence ( table  2 ) .
the impact of gastric protective medications on gastroduodenal toxicity is presented in table  3 . compared to patients not receiving any gastroprotective medication ,
any treatment was associated with significantly lower rates of bleeding and mucosal injury ( p<0.01 for both comparisons ) .
similarly , use of a ppi alone was significantly more protective against bleeding and mucosal injury than non - use of any medicine ( p<0.01 for both comparisons ) .
in terms of combination therapy , patients taking a ppi or h2ra plus an mp agent showed significantly better outcomes in terms of mucosal injury compared to patients taking no medication .
use of a ppi / h2ra plus rebamipide was associated with a better overall outcome ( bleeding , mucosal injury ) than acid suppressants plus other mps , although the rate of h. pylori infection , a significant confounding factor , did not differ between two groups ( table  4 ) .
aspirin , even in low doses , induces gastrointestinal mucosal injury and hemorrhage , which limits its clinical use .
lda - induced gastrointestinal toxicity has become a big problem in japan as well as other countries .
a case - control study of hemorrhagic peptic ulcer patients indicated that the risk of lda for bleeding from ulcers is similar to other nsaids .
other reports also support the high prevalence of gastroduodenal mucosal injury in lda users [ 5 , 6 ] .
although information is limited in japanese patients , data indicate that effective treatments are needed for lda - related gastrointestinal toxicity in japanese patients as well .
however , in cases in which lda use is required , such as after placement of a drug - eluted coronary stent , protection of gastrointestinal mucosa against lda - injury is important .
proven treatment for lda - related mucosal injury includes co - administration of a ppi and eradication of h. pylori . because these treatments are comparable in efficacy , but do not provide complete protection , other therapeutic options are needed .
co - administration of acid suppressants and other gastroprotective medicines is one possible treatment , although we can find only one report regarding this treatment .
the present data clearly showed the effectiveness of acid suppressants , especially ppi , for suppressing lda - induced mucosal damage , which is consistent with previous data .
patients receiving any gastroprotective medicine suffered from mucosal injury significantly less frequently than those who did not receive any medication .
rebamipide provides it gastric mucoprotective effect via different mechanisms from acid suppressants , which affect not only the upper gastrointestinal tract but also other intestinal organs [ 1015 ] .
rebamipide stimulates the production of prostaglandins and epidermal growth factor , preventing h. pylori - elicited neutrophil - induced mucosal injury and decreasing free radical levels [ 16 , 17 ] .
clinically , the efficacy against nsaid - induced gastric injury is reported as comparable to that of low - dose famotidine , one of h2ra .
the present results suggest the new potential for use of rebamipide with a ppi and h2ra to protect against lda - related intestinal damage .
the limitations of the present study include the retrospective study design , the small sample number , and the fact that all patients were drawn from a single institute . because selection bias may have affected the present results , data should be interpreted carefully .
a prospective trial is needed to clarify the effect of rebamipide added to ppis and h2ra therapy on the prevention of aspirin - induced gi injury .
 the present study was conducted to investigate the prevalence of mucosal injury in patients taking low - dose aspirin in japan and examine the effect of gastric mucoprotective drugs on aspirin - related gastroduodenal toxicity . 
 we selected 530 patients who had taken low - dose aspirin for 1 month or more after undergoing esophagogastroduodenoscopy from 2005 through 2006 at teikyo university hospital , tokyo , japan . 
 endoscopic records were retrospectively reviewed to determine the presence of massive bleeding and mucosal injury ( ulcer or erosion ) . 
 the influence of clinical factors , including co - administration of gastroprotective drugs , was also examined . 
 hemorrhage was observed in 25 patients ( 3.7% ) and mucosal injury ( 36.2% ) in 192 patients . 
 the presence of helicobacter pylori antibody was a significant risk factor associated with mucosal injury . 
 patients taking any gastroprotective drug showed a significantly lower rate of mucosal injury than those not taking these drugs . 
 patients taking rebamipide concomitantly with proton pump inhibitors or histamine 2 receptor antagonists had mucosal injury less frequently than those taking acid suppressants plus other mucoprotective drugs . in conclusion , 
 these results show the possible gastroprotective effects of rebamipide , suggesting that it may be a good choice in aspirin users with gastroduodenal toxicity that is not suppressed by acid suppressants alone . 
Introduction
Materials and Methods
Results
Discussion