Aspirin use and risk of bleeding complications

There is a small increase in the incidence of haemorrhagic stroke in patients taking regular aspirin. This effect is larger in patients taking aspirin as a primary prevention of stroke rather than secondary prevention. In neither case is the increased incidence of stroke statistically significant.

There is a significant increase in the rate of extracranial haemorrhage in patients taking aspirin.

Gastrointestinal haemorrhage is a dose-dependent problem:

• 3% of patients taking 300 mg/day bleed
• 5% of patients taking 1200 mg/day bleed
• doses below 100 mg/day are still associated with an increased rate of bleeding - a meta-analysis of 31 trials (n=192,036) identified an approximate three-fold-lower rate of bleeding complications for patients taking aspirin doses of <100mg daily compared with those taking 100–200mg or >200mg doses (1)

Risk of bleeding with particular reference to low dose aspirin (2):

• relative risk of major gastrointestinal bleeding with low-dose aspirin in a meta-analysis of placebo-controlled trials of vascular protection was 2.07 (95% CI: 1.61-2.66)
  • absolute rate increase with aspirin above placebo was 0.12% per year (95% CI: 0.07-0.19%) with a number-needed-to-harm of 833 patients (95% CI: 526-1429)
  • meta-analysis of aspirin 50-1500 mg daily reported an odds ratio for any gastrointestinal bleeding of 1.68 (95% CI: 1.51-1.88) with an number-needed-to-harm at 1 year of 247
  • relative risk of hospitalization for upper gastrointestinal bleeding with low-dose aspirin in a large Danish cohort study was 2.6 (95% CI: 2.2-2.9) with an absolute annual incidence of 0.6%
  • factors that may increase the risk of gastrointestinal bleeding include prior history of ulcers or gastrointestinal bleeding, corticosteroid use, anticoagulant therapy and addition of a non-aspirin non-steroidal anti-inflammatory drug
  • the author concluded that when determining whether low-dose aspirin is appropriate for an individual patient, the cardiovascular benefit must be weighed against the potential for clinical events such as gastrointestinal bleeding

Reference:

1. Serebruany VL, Steinbuhl SR, Berger PB, et al. Analysis of risk of bleeding complications after different doses of asprin in 192,036 patients enrolled in 31 randomised controlled trials. Am J Cardiol 2005;95:1218–22
2. Laine L. Review article: gastrointestinal bleeding with low-dose aspirin - what's the risk? Aliment Pharmacol Ther. 2006 Sep 15;24(6):897-908