Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis

doi:10.1136/bmj.321.7270.1183

BMJ 2000;321:1183-1187 ( 11 November )

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Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis

Editorial by Tramèr

Sheena Derry, research assistant, Yoon Kong Loke, clinical lecturer in clinical pharmacology.

Department of Clinical Pharmacology, University of Oxford, Radcliffe Infirmary, Oxford OX2 6HE

Correspondence to: Y K Loke yoon.loke{at}clinpharm.ox.ac.uk

Objectives: To assess the incidence of gastrointestinalhaemorrhage associated with long term aspirin therapy and to determinethe effect of dose reduction and formulation on the incidenceof suchhaemorrhage.
Design: Meta-analysis of 24 randomised controlledtrials (almost 66 000participants).
Intervention: Aspirin compared with placebo or no treatment,for a minimum of oneyear.
Main outcome measures: Incidence of gastrointestinalhaemorrhage.
Results: Gastrointestinal haemorrhage occurred in 2.47%of patients taking aspirin compared with 1.42% taking placebo(odds ratio 1.68; 95% confidence interval 1.51 to 1.88); the numberneeded to harm was 106 (82 to 140) based on an average of 28 months'therapy. At doses below 163 mg/day, gastrointestinal haemorrhageoccurred in 2.30% of patients taking aspirin compared with 1.45%taking placebo (1.59; 1.40 to 1.81). Meta-regression showed norelation between gastrointestinal haemorrhage and dose. For modifiedrelease formulations of aspirin the odds ratio was 1.93 (1.15to 3.23).
Conclusions: Long term therapy with aspirin is associatedwith a significant increase in the incidence of gastrointestinalhaemorrhage. No evidence exists that reducing the dose or usingmodified release formulations would reduce the incidence of gastrointestinalhaemorrhage.

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Hawkey, C J, Langman, M J S (2003). Non-steroidal anti-inflammatory drugs: overall risks and management. Complementary roles for COX-2 inhibitors and proton pump inhibitors. Gut 52: 600-608 [Abstract] [Full text]
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Lauer, M. S. (2002). Aspirin for Primary Prevention of Coronary Events. NEJM 346: 1468-1474 [Full text]
Hayden, M., Pignone, M., Phillips, C., Mulrow, C. (2002). Aspirin for the Primary Prevention of Cardiovascular Events: A Summary of the Evidence for the U.S. Preventive Services Task Force. ANN INTERN MED 136: 161-172 [Abstract] [Full text]
Drummond, A., Kwok, S., Morgan, J., Durrington, P.N. (2002). Costs of aspirin and statins in general practice. QJM 95: 23-26 [Abstract] [Full text]
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LOWE, G. D O (2001). Who should take aspirin for primary prophylaxis of coronary heart disease?. Heart 85: 245-246 [Full text]
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