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Prevention of damage induced by aspirin in the GI tract

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Low-dose aspirin (325 mg or less) alone and in combination with other antiplatelet agents is widely used for the management of cardiovascular disease. Although the risk with low-dose aspirin alone is less than Nonsteroidal anti-inflammatory drugs (NSAIDs), given widespread use, aspirin related toxicity has become a substantial health care problem due to acute and chronic GI bleeding. A variety of strategies are currently available to minimize the risk of developing upper GI side effects of aspirin. Agents that have efficacy include oral prostaglandin analogues, H2 receptor antagonists and proton pump inhibitors. PPIs appear to be the most effective strategy, with the least side effects and the convenience of once daily dosing. The substitution of another antiplatelet agent such as clopidogrel for aspirin alone does not appear to provide a safer alternative to low-dose aspirin for patients at GI risk. Small bowel injury can occur with aspirin and can be assessed with capsule endoscopy; however, no strategy is known to reduce this potential toxicity in clinical practice.

Introduction

The mechanism of aspirin related GI toxicity as well as its epidemiology has been well described in previous chapters in this book. At low-dose (325 mg or less) aspirin predominantly inhibits the cyclooxygenase (COX)-1 isoform in the GI mucosa leading to ulcerogenic effects. Aspirin can also promote bleeding from pre-existing lesions in the GI tract, such as tumours or diverticulae due to impaired platelet function. Higher doses of aspirin have considerable dose related toxicity along despite potent analgesic properties, and have been largely abandoned in clinical practice due to the development of less toxic NSAIDs with more favourable risk benefit profiles. This chapter will focus on the data on strategies to reduce low-dose aspirin risk to the GI tract. The major focus will be on upper GI ulceration and bleeding. Injury to the small bowel and what little we know about strategies to reduce it will be touched upon as well.

There are no known strategies to reduce the risk of aspirin related haemorrhage due to its antiplatelet effect leading to bleeding from an effect on a pre-existing lesion. Anecdotally, this can be of potential benefit as well as harm, for example early detection of an early colon cancer due to presentation with overt bleeding when aspirin is initiated for cardiovascular therapy. Restricting aspirin use to only those patients in whom the benefits exceed its risk, such as secondary prevention of CV events and those with elevated CV risk for primary prevention is a key strategy to limit aspirin’s GI adverse events [1]. Although debated, the lowest effective aspirin dose (75–81 mg) can minimize GI side effects compared to higher doses; these and other strategies such as Helicobacter Pylori eradication are discussed in detail by other authors in this monograph.

Section snippets

Gastroprotective agents

Although somewhat less well studied than full dose NSAID therapy, strategies to reduce ulcers and bleeding from low-dose aspirin have been evaluated in endoscopic as well as outcome studies, both observational as well as randomized controlled trials. Key studies in each category will be reviewed to support existing evidence based recommendations for therapy.

As prostaglandin depletion is the central mechanism for ulcer development due to COX inhibitors, replacement therapy with the synthetic

Conflict of interest statement

Dr Scheiman is a consultant to Astra-Zeneca, Novartis and Pozen, Inc.

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