Editorial: lower gastrointestinal bleeding and low‐dose aspirin—authors’ reply

Abstract

We deeply appreciate the comments from Dr. Taha concerning our recent work.1,2 The risk of lower gastrointestinal bleeding (LGIB) in aspirin users is usually investigated in case-control studies. 3 However, little is known about the incidence and prevalence rates of LGIB among aspirin users. Therefore, we collected a cohort of new aspirin users and matched controls to estimate the actual risk of LGIB. We agree that, ideally, patients using drugs with bleeding potential should be excluded to avoid the confounding effects upon LGIB. However, the proportion of pro-bleeding drug use in clopidogrel users was higher than that in clopidogrel non-users in a nationwide study. 4 It is possible that users of antiplatelet agents might seek medical help for comorbidities, thus increasing the probability of pro-bleeding drug use. Finally, we chose to control the confounding factors via statistical methods because we believed that these samples were more close to patients in practice. Aspirin use remained an independent risk factor for LGIB after adjustments for age, gender, comorbidities, nonsteroidal anti-inflammatory drugs (NSAIDs), clopidogrel, ticlopidine, warfarin, steroids and selective serotonin reuptake inhibitors. 2 This indicates that aspirin is significantly associated withLGIB although the risk might be overestimated when patients using drugs with bleeding potential were not excluded. More studies excluding patients with bleeding diathesis and using pro-bleeding drugs are needed to clarify the actual risk of aspirin-induced LGIB. The second comment raised is the impact of antisecretory agents on LGIB in aspirin users.There is growing evidence on the association between proton pump inhibitors (PPIs) and LGIB. 5 Nevertheless, the association does not necessarily suggest that PPIs directly cause LGIB because PPI use usually indicates a poor comorbidity status, which increases the probability ofLGIB. However, more small intestinal injury has been observed in patients using PPIs plus NSAIDs than patients using NSAIDs alone. 6 PPIs might also exacerbate NSAID and low-dose aspirin-associated small bowel injury by inducing changes in the intestinal microbiota. 7,8 Moreover, probiotic use significantly decreases the incidence of small intestine mucosal injury in patients using PPIs and aspirin. 8 These studies indicate that PPIs might indirectly induce injury of the lower GI tract and predispose the mucosa towards bleeding in aspirin users. Another important issue is to decrease the risk of LGIB in aspirin users in whom PPI therapy may be considered. Prostaglandin analogue use is an alternative strategy to prevent aspirin-induced peptic ulcers and was effective in the treatment of aspirin-induced enteropathy in a pilot study. 9 Dr. Taha has conducted an interesting randomised controlled trial on healing of small bowel mucosal ulcers in response to misoprostol in aspirin or NSAIDs users 10 and we look forward to the results. Finally, identifying low-dose aspirin users at low risk for upper GI bleeding to avoid inappropri...