Can low-dose aspirin (acetylsalicylic acid) cause gastrointestinal (GI) bleeding?

Can Low-Dose Aspirin Cause Gastrointestinal Bleeding?

Yes, low-dose aspirin can definitely cause gastrointestinal bleeding, with studies showing it increases the risk of major GI bleeding by approximately 2 times compared to non-users. 1

Risk of GI Bleeding with Low-Dose Aspirin

Low-dose aspirin (75-325 mg daily) significantly increases the risk of gastrointestinal bleeding through its antiplatelet effects:

• A meta-analysis of 35 randomized controlled trials found that aspirin at doses of 75-325 mg daily increased the hazard ratio for major gastrointestinal bleeding to 1.31 (95% CI 1.21-1.42) 1
• For average-risk individuals without bleeding history or concurrent anticoagulants, this translates to one or two GI bleeding events per 1,000 person-years 1
• The relative risk of upper GI bleeding with low-dose aspirin in a large cohort study was 2.6 (95% CI 2.2-2.9) 2
• Even at the lowest doses (81 mg/day), aspirin can cause endoscopic ulcers in approximately 7% of users within 12 weeks 1

Dose-Response Relationship

The risk of GI bleeding with aspirin demonstrates a clear dose-response relationship:

• Higher doses of aspirin (300-325 mg) carry greater bleeding risk than lower doses (75-162.5 mg) 1
• A prospective cohort study of nearly 33,000 men showed that compared to non-users, the risk of upper GI bleeding increased progressively: 3
  • 1.05 for 0.5-1.5 tablets/week
  • 1.31 for 2-5 tablets/week
  • 1.63 for 6-14 tablets/week
  • 2.40 for >14 tablets/week

Risk Factors That Increase Bleeding Risk

Several factors substantially increase the risk of GI bleeding in aspirin users:

• Advanced age (risk increases approximately 4% per year) 1
• History of previous peptic ulcer or GI bleeding (most significant risk factor, with odds ratio up to 13.5) 1
• Concurrent use of:
  • Other NSAIDs (increases risk approximately 4 times) 1
  • Anticoagulants 1
  • Corticosteroids 1
  • Selective serotonin reuptake inhibitors 4
• Helicobacter pylori infection 5
• Uncontrolled hypertension 1

Timing of Bleeding Risk

The risk of GI bleeding with aspirin is not uniform over time:

• A meta-analysis by Rothwell found that major extracranial bleeding (mainly gastrointestinal) occurred primarily in the short term (<3 years) following initiation of aspirin 1
• After 3 years, low-dose aspirin (<300 mg) was not significantly associated with continued risk of such events 1

Protective Strategies

For patients who require aspirin therapy but are at increased risk for GI bleeding:

• Use the lowest effective dose of aspirin (75-100 mg/day) 4
• Consider co-therapy with a proton pump inhibitor (PPI) for high-risk patients 1
  • Omeprazole has been shown to be more effective than ranitidine in healing and preventing ulcers in NSAID users 1
  • For patients with prior ulcer bleeding, the combination of aspirin plus PPI is superior to switching to clopidogrel alone 1
• H. pylori eradication may be beneficial in patients with history of ulcers 5

Important Caveats

• Enteric-coated or buffered aspirin preparations do not reduce the risk of major upper GI bleeding 1
• Discontinuing aspirin after a GI bleeding event may increase mortality - a study showed doubling of all-cause mortality in patients who discontinued aspirin after GI bleeding 6
• The decision to use aspirin should balance cardiovascular benefits against bleeding risks, especially in older adults 1

For patients experiencing GI bleeding while on aspirin, immediate medical attention is required, as indicated by symptoms such as black stools, vomiting blood, or persistent abdominal pain 7.