Nonsteroidal Anti-Inflammatory Drugs and Lower Gastrointestinal Complications

Service of Digestive Diseases, University Hospital, University of Zaragoza, Instituto Aragonés de Ciencias de la Salud, CIBERehd, C/San Juan Bosco 15, 50009 Zaragoza, Spain.
Gastroenterology clinics of North America (Impact Factor: 2.82). 07/2009; 38(2):333-52. DOI: 10.1016/j.gtc.2009.03.007
Source: PubMed


In addition to the upper GI tract, NSAIDs can damage the small bowel and the colon. NSAID enteropathy is frequent and may be present in more than 60% of patients taking these drugs long term. In most cases, damage is subclinical, including increased mucosal permeability, inflammation, erosions, ulceration, but other more serious clinical outcomes such as anemia, and overall bleeding, perforation, obstruction, diverticulitis and deaths have also been described. The magnitude of these serious outcomes from the lower GI tract is not well defined, but recent data suggest that they may be as frequent and severe as upper GI complications. Contrary to what happens in the upper GI tract, treatment and prevention of NSAID enteropathy is difficult, since the pathogenic mechanisms are different and not well understood. Among other options, misoprostol, antibiotics, and sulphasalazine have been proved to be effective in animal models, but they have not been properly tested in humans. Selective COX-2 inhibition is emerging as a potential alternative to tNSAIDs in the prevention of damage in the lower GI tract in rheumatologic patients. Preliminary studies in healthy volunteers have shown that these drugs are associated with no or less small bowel damage than tNSAIDs plus PPI, although their long-term effects in patients need to be properly tested. Post hoc analysis of previous outcome studies focused on complications of upper GI tract or cardiovascular events have shown contradictory results. Data from one ongoing trial comparing celecoxib versus diclofenac plus PPI and examining serious outcomes from the whole GI tract will probably provide new insights in this area.

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    • "Although the efficacy of nonselective NSAIDs in arthritis is well established, use of these agents is associated with numerous adverse events, including upper and lower gastrointestinal (GI) toxicity [4] [5] [6] [7] [8] [9]. All prescription NSAIDs have the same warning for serious GI events from the US Food and Drug Administration [10]. "
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    ABSTRACT: Compare effectiveness of celecoxib versus diclofenac plus omeprazole in improving arthritis signs and symptoms in patients at high gastrointestinal (GI) risk who were enrolled in the CONDOR (Celecoxib vs Omeprazole and Diclofenac in Patients With Osteoarthritis and Rheumatoid Arthritis) trial. CONDOR was a 6-month, prospective, double-blind, triple-dummy, parallel-group, randomized, multicenter trial comparing celecoxib 200 mg twice daily versus diclofenac slow release (SR) 75 mg twice daily plus omeprazole 20 mg daily. Patients were Helicobacter pylori negative, had osteoarthritis (OA) or rheumatoid arthritis (RA), were aged ≥60 years, were with or without a history of gastroduodenal ulceration, or were ≥18 years with previous gastroduodenal ulceration. Patients' Global Assessment of Arthritis was determined at each study visit. A total of 4484 patients were randomized to treatment (2238 celecoxib, 2246 diclofenac SR) and included in the intention-to-treat analyses. Least squares mean (LSM) (standard error [SE]) for Patients' Global Assessment of Arthritis was 3.219 (0.017) and 3.221 (0.017) at baseline for celecoxib and diclofenac SR (p=0.90). Improvement in both groups was similar in months 2, 4, and 6; at month 1 the LSM (SE) was 2.647 (0.017) and 2.586 (0.017) for celecoxib and diclofenac (p=0.0025). LSM difference (SE) from baseline to final visit demonstrated an improvement of 0.75 (0.02) in celecoxib-treated patients and 0.77 (0.02) in diclofenac SR-treated patients (p=0.42). Celecoxib and diclofenac plus omeprazole were shown to have similar efficacy in patients with OA and/or RA at increased GI risk who were enrolled in the CONDOR trial. Trial was registered under identifier NCT00141102.
    Full-text · Article · Nov 2013 · The Open Rheumatology Journal
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    • "Nonsteroidal anti-inflammatory drug-(NSAID-) induced lower gastrointestinal (GI) injury is more common than NSAID-associated gastropathy [1] [2] [3] [4] [5] [6] [7] [8]. Historically, this has been given little clinical attention since NSAID-induced enteropathy is usually asymptomatic and is not easily detected using most common diagnostic testing modalities [9] [10]. Recently, through the introduction of capsule endoscopy and device-assisted endoscopy, NSAID enteropathy has become a popular topic of study [11] particularly since NSAID enteropathy is one of the most common causes of obscure GI bleeding [11] [12]. "
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    ABSTRACT: The injurious effects of NSAIDs on the small intestine were not fully appreciated until the widespread use of capsule endoscopy. It is estimated that over two-thirds of regular NSAID users develop injury in the small intestinal injuries and that these injuries are more common than gastroduodenal mucosal injuries. Recently, chronic low-dose aspirin consumption was found to be associated with injury to the lower gut and to be a significant contributing factor in small bowel ulceration, hemorrhage, and strictures. The ability of aspirin and NSAIDs to inhibit the activities of cyclooxygenase (COX) contributes to the cytotoxicity of these drugs in the gastrointestinal tract. However, many studies found that, in the small intestine, COX-independent mechanisms are the main contributors to NSAID cytotoxicity. Bile and Gram-negative bacteria are important factors in the pathogenesis of NSAID enteropathy. Here, we focus on a promising strategy to prevent NSAID-induced small intestine injury. Selective COX-2 inhibitors, prostaglandin derivatives, mucoprotective drugs, phosphatidylcholine-NSAIDs, and probiotics have potential protective effects on NSAID enteropathy.
    Full-text · Article · Sep 2013 · Gastroenterology Research and Practice
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    • "Table constructed using data from [28]. NSAID, nonsteroidal anti-inflammatory drug. "
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    ABSTRACT: NSAIDs are among the most commonly used drugs worldwide and their beneficial therapeutic properties are thoroughly accepted. However, they are also associated with gastrointestinal (GI) adverse events. NSAIDs can damage the whole GI tract including a wide spectrum of lesions. About 1 to 2% of NSAID users experienced a serious GI complication during treatment. The relative risk of upper GI complications among NSAID users depends on the presence of different risk factors, including older age (>65 years), history of complicated peptic ulcer, and concomitant aspirin or anticoagulant use, in addition to the type and dose of NSAID. Some authors recently reported a decreasing trend in hospitalizations due to upper GI complications and a significant increase in those from the lower GI tract, causing the rates of these two types of GI complications to converge. NSAID-induced enteropathy has gained much attention in the last few years and an increasing number of reports have been published on this issue. Current evidence suggests that NSAIDs increase the risk of lower GI bleeding and perforation to a similar extent as that seen in the upper GI tract. Selective cyclooxygenase-2 inhibitors have the same beneficial effects as nonselective NSAIDs but with less GI toxicity in the upper GI tract and probably in the lower GI tract. Overall, mortality due to these complications has also decreased, but the in-hospital case fatality for upper and lower GI complication events has remained constant despite the new therapeutic and prevention strategies.
    Preview · Article · Jul 2013 · Arthritis Research & Therapy
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