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 gastrointestinal haemorrhage associated with long term aspirin therapy and to determine the effect of dose reduction and formulation on the incidence of such haemorrhage.
Design: Meta-analysis of 24 randomised controlled trials (almost 66 000 participants).
Intervention: Aspirin compared with placebo or no treatment, for a minimum of one year.
Main outcome measures: Incidence of gastrointestinal haemorrhage.
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 number needed to harm was 106 (82 to 140) based on an average of 28 months' therapy. At doses below 163 mg/day, gastrointestinal haemorrhage occurred in 2.30% of patients taking aspirin compared with 1.45% taking placebo (1.59; 1.40 to 1.81). Meta-regression showed no relation between gastrointestinal haemorrhage and dose. For modified release formulations of aspirin the odds ratio was 1.93 (1.15 to 3.23).
Conclusions: Long term therapy with aspirin is associated with a significant increase in the incidence of gastrointestinal haemorrhage. No evidence exists that reducing the dose or using modified release formulations would reduce the incidence of gastrointestinal haemorrhage.


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  • Rahme, E., Bardou, M., Dasgupta, K., Toubouti, Y., Ghosn, J., Barkun, A. N. (2007). Hospitalization for gastrointestinal bleeding associated with non-steroidal anti-inflammatory drugs among elderly patients using low-dose aspirin: a retrospective cohort study. Rheumatology (Oxford) 46: 265-272 [Abstract] [Full text]  
  • Sung, J. J Y (2006). Combining aspirin with antithrombotic agents.. BMJ 333: 712-713 [Full text]  
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  • Vallurupalli, N. G., Goldhaber, S. Z. (2006). Gastrointestinal Complications of Dual Antiplatelet Therapy. Circulation 113: e655-e658 [Full text]  
  • Goel, A., Gasche, C., Boland, C. R. (2005). Chemoprevention Goes Gourmet: Different Flavors of NO-Aspirin. Mol. Interv. 5: 207-210 [Abstract] [Full text]  
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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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  • Weisman, S. M., Graham, D. Y. (2002). Evaluation of the Benefits and Risks of Low-Dose Aspirin in the Secondary Prevention of Cardiovascular and Cerebrovascular Events. Arch Intern Med 162: 2197-2202 [Abstract] [Full text]  
  • Lauer, M. S. (2002). Aspirin for Primary Prevention of Coronary Events. NEJM 346: 1468-1474 [Full text]  
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  • 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]  
  • (2001). Other Articles Noted. Evid. Based Nurs. 4: E1-11 [Full text]  
  • LOWE, G. D O (2001). Who should take aspirin for primary prophylaxis of coronary heart disease?. Heart 85: 245-246 [Full text]  
  • (2001). Aspirin and GI Hemorrhage: A Consistent Association. Journal Watch Cardiology 2001: 13-13 [Full text]  
  • (2001). Risk for GI Hemorrhage Associated with Long-Term Aspirin Use. JWatch Neurology 2001: 6-6 [Full text]  
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