Gastroduodenal toxicity of low-dose acetylsalicylic acid: a comparison with non-steroidal anti-inflammatory drugs

Abstract

Background:

Low-dose acetylsalicylic acid (ASA; aspirin; 75–325 mg/day) is effective for the prevention of cardiovascular events, and its use in this indication is rapidly increasing. However, the use of ASA and, indeed, other non-steroidal anti-inflammatory drugs (NSAIDs) is limited by the incidence of adverse gastroduodenal events.

Objectives and scope:

To review the clinical evidence for, and the pharmacodynamic basis of, ASA-induced gastroduodenal toxicity in comparison with NSAIDs, and address the question of whether low-dose ASA is ‘safe’ from a gastroduodenal perspective. This was a narrative, descriptive review, rather than a formal systematic review.

Findings:

Adverse gastroduodenal effects, which are well known to occur with NSAIDs, are also prevalent in patients receiving low-dose ASA for cardiovascular protection even at doses as low as 75 mg/day. The risk of gastroduodenal toxicity is particularly high among ‘at-risk’ low-dose ASA patients (aged >70 years, previous ulcer or upper gastrointestinal bleeding and users of antiplatelets or NSAIDs). There are important differences in the mechanism of ASA-induced gastroduodenal toxicity, relative to NSAIDs. These differences include the effects on the cyclooxygenase (COX)-1 isoenzyme, local effects on the gastroduodenal mucosa specific to ASA and a reduction in platelet aggregation.

Conclusion:

Data suggest that ASA causes significant gastroduodenal damage even at the low doses used for cardiovascular protection. These effects (both systemic and possibly local) may be pharmacodynamically distinct from the gastroduodenal toxicity seen with NSAIDs. Studies are required to establish strategies for improving the tolerability of low-dose ASA, allowing patients to continue to benefit from the cardiovascular protection associated with such therapy.

Key words: :

• Acetylsalicylic acid (ASA)
• Gastroduodenal toxicity
• Non-steroidal anti-inflammatory drugs

Transparency

Declaration of funding

This study was supported by AstraZeneca.

Declaration of financial/other relationships

N.D.Y. has disclosed that he is an advisor to AstraZeneca (and previously to Merck Sharp & Dohme and Pfizer). C.J.H. has disclosed that he has received research funding and/or honoraria from AstraZeneca, and other pharmaceutical companies. W.B. and J.N. have disclosed that they are employees of AstraZeneca.

Peer reviewers may receive honoraria from CMRO for their review work. Peer Reviewers 1 and 2 have disclosed no relevant financial relationships.

Acknowledgements

The authors thank Claire Byrne and Steve Winter, from Wolters Kluwer Health (Chester, UK) who provided medical writing support funded by AstraZeneca.