Occult vs. overt upper gastrointestinal bleeding – inverse relationship and the use of mucosal damaging and protective drugs

Abstract

SUMMARY BackgroundWhile efforts have focused on the prevention of overt upper gastrointestinal bleeding (UGIB), little is known about occult GIB, which might also originate from sites not protected by acid inhibition.

Misoprostol for small bowel ulcers in patients with obscure bleeding taking aspirin and non-steroidal anti-inflammatory drugs (MASTERS): a randomised, double-blind, placebo-controlled, phase 3 trial

“…As a result of effective acidinhibiting drugs, the incidence of upper gastrointestinal bleeding has decreased.1-3,6 By contrast, diagnosis of ulcers and erosions of the small bowel among individuals taking aspirin and NSAIDs has increased; these patients have few treatment options because prostaglandin production (rather than excess acid) is the primary driver of ulcer pathogenesis in the alkaline environment of the small bowel. [3][4][5][6][7][8][9][10][11]14,15 Since aspirin and NSAIDs are known to cause ulcers by suppressing mucosal prostaglandin synthesis,3-11 we chose to include patients taking these drugs in our study. These factors highlight the importance of identifying a drug that can be used to heal small bowel ulcers in patients who take aspirin and NSAIDs.…”

“…[3][4][5][6] We previously found that the annual incidence of occult or obscure gastrointestinal bleeding among individuals in southwest Scotland increased from 243·1 per 100 000 individuals in 2007, to 292·8 per 100 000 individuals in 2012, and the corresponding incidence of upper gastrointestinal bleeding decreased from 140·1 per 100 000 individuals in 2007, to 88·0 per 100 000 individuals in 2012. 6 These changes were associated with an increase in the number of prescriptions of non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, and proton-pump inhibitors between 2007 and 2012. 6 Obscure gastrointestinal bleeding mainly originates from the small bowel, and its incidence has been rising, which might be explained by the widespread use of low-dose aspirin and NSAIDs.3- 6 The diagnosis of small bowel ulcers in patients taking these drugs has been facilitated by the introduction of video capsule endoscopy.7-9 Small bowel ulcers develop as a result of the suppression of mucosal prostaglandin synthesis by aspirin or NSAIDs,7-9 and because of the alkaline environment of the small bowel, these ulcers do not respond to acid inhibitors.7 A pilot study10 found that small bowel mucosal lesions associated with aspirin use healed following treatment with misoprostol (a prostaglandin analogue) in four of seven patients.…”

“…Bleeding in the gastrointestinal tract is generally classified according to anatomical location-ie, upper gastrointestinal bleeding (ie, proximal to the ligament of Treitz) or lower gastrointestinal bleeding.1-3 The incidence of upper gastrointestinal bleeding has been declining since 2007, largely due to the use of proton-pump inhibitors and the eradication of Helicobacter pylori infection, and the diagnosis and management of obscure gastrointestinal bleeding, which is distinct from upper and lower gastrointestinal bleeding, has become a focus of research. [3][4][5][6] This condition is common in people with iron deficiency anaemia or overt or occult gastrointestinal bleeding, in whom no potential source of bleeding is found on oesophagogastroduodenoscopy or colonoscopy. [3][4][5][6] We previously found that the annual incidence of occult or obscure gastrointestinal bleeding among individuals in southwest Scotland increased from 243·1 per 100 000 individuals in 2007, to 292·8 per 100 000 individuals in 2012, and the corresponding incidence of upper gastrointestinal bleeding decreased from 140·1 per 100 000 individuals in 2007, to 88·0 per 100 000 individuals in 2012.…”

“…[3][4][5][6] This condition is common in people with iron deficiency anaemia or overt or occult gastrointestinal bleeding, in whom no potential source of bleeding is found on oesophagogastroduodenoscopy or colonoscopy. [3][4][5][6] We previously found that the annual incidence of occult or obscure gastrointestinal bleeding among individuals in southwest Scotland increased from 243·1 per 100 000 individuals in 2007, to 292·8 per 100 000 individuals in 2012, and the corresponding incidence of upper gastrointestinal bleeding decreased from 140·1 per 100 000 individuals in 2007, to 88·0 per 100 000 individuals in 2012. 6 These changes were associated with an increase in the number of prescriptions of non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, and proton-pump inhibitors between 2007 and 2012.…”

“…6 These changes were associated with an increase in the number of prescriptions of non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, and proton-pump inhibitors between 2007 and 2012. 6 Obscure gastrointestinal bleeding mainly originates from the small bowel, and its incidence has been rising, which might be explained by the widespread use of low-dose aspirin and NSAIDs.3- 6 The diagnosis of small bowel ulcers in patients taking these drugs has been facilitated by the introduction of video capsule endoscopy.7-9 Small bowel ulcers develop as a result of the suppression of mucosal prostaglandin synthesis by aspirin or NSAIDs,7-9 and because of the alkaline environment of the small bowel, these ulcers do not respond to acid inhibitors.7 A pilot study10 found that small bowel mucosal lesions associated with aspirin use healed following treatment with misoprostol (a prostaglandin analogue) in four of seven patients. Preliminary data11 have shown that misoprostol was more effective than placebo for the treatment of small bowel ulcers associated with aspirin use.…”