Managing the Adverse Effects of Nonsteroidal Anti-inflammatory Drugs

Paola Patrignani; Stefania Tacconelli; Annalisa Bruno; Carlos Sostres; Angel Lanas


Expert Rev Clin Pharmacol. 2011;4(5):605-621. 

In This Article

Management of GI Risk With Asprin

Aspirin use is being recognized as one of the main reason for hospitalizations due to GI bleeding.[129] It is well known that low-dose aspirin increases the risk of UGIB. A meta-analysis of 14 randomized clinical trials, recently published,[130] has shown an absolute rate increase of major UGIB with aspirin above placebo of 0.12% per year (95% CI: 0.07–0.19%). Risk factors for GI bleeding with asprin include age ≥70, ulcer history, co-therapy with NSAIDs, coxibs, anticoagulants or other antiplatelet agents.[35] Those at risk should be on GI prevention therapy.[131] Some key strategies have been proposed for minimizing the upper GI side effects of low-dose aspirin. These are the use of an alternative platelet inhibitor, such as clopidogrel, the use of co-therapy with a gastroprotective agent and eradicating H. pylori.

Cardiology guidelines recommend the antithrombotic agent clopidogrel for patients who are unable to take aspirin due to previous GI intolerance. However, in clinical practice two case–control studies, have found that clopidogrel is associated with a similar RR of ulcer bleeding to low-dose aspirin.[132,133] Two clinical trials have also found that high-risk patients on clopidogrel alone have an unacceptable rate of bleeding ulcers.[132,133]

Co-therapy with gastroprotective agents such as PPI, H2-receptor antagonists (H2-RAs) are currently the most widely used strategy to reduce this GI risk with aspirin.[99,100,134] A recent study showed that high-dose famotidine was effective in the prevention of gastric and duodenal ulcers in patients taking low-dose aspirin.[135] However, another study by Ng et al. concluded that in patients with aspirin-related peptic ulcers/erosions, high-dose famotidine therapy was inferior to pantoprazole standard doses in preventing recurrent dyspeptic symptoms or ulcer bleeding.[136] One study reported that the risk of recurrent ulcer bleeding in low-dose aspirin users treated with a PPI was similar to that of patients receiving eradication therapy composed of bismuth subcitrate, tetracycline and metronidazole (0.9 vs 1.9%; p = nonsignificant).[98] However, in another study with high-risk patients who underwent H. pylori eradication, lansoprazole was more effective than placebo in the prevention of ulcer bleeding recurrence in patients who receive low-dose aspirin for 12 months.[137] Esomeprazole associated with low-dose aspirin was also associated with a very low recurrence rate of ulcer rebleeding when compared with clopidogrel alone.[138] In a recent case–control study by Lanas et al., PPIs reduced the risk of upper GI complications. PPI use was associated with risk reduction among both tNSAID and low-dose aspirin users and among patients taking NSAIDs and clopidogrel.[99]

Based on all these studies, the American College of Cardiology Foundation/American College of Gastroenterology/American Heart Association 2008 Expert Consensus Document[131] supports the use of PPIs instead of double-dose H2RAs in preventing recurrent low-dose aspirin-related injury.


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