What is the risk of intracranial hemorrhage in patients on aspirin (acetylsalicylic acid)?

Risk of Intracranial Hemorrhage in Patients on Aspirin

The risk of intracranial hemorrhage (ICH) in patients taking aspirin is low but measurable: approximately 1 additional ICH per 1,000 patients per year in high-risk cardiovascular populations, with the absolute excess risk being less than 0.1% annually. 1

Quantified Risk by Population

Primary Prevention (Low-Risk Patients)

• Low-dose aspirin increases ICH risk by approximately 2 additional cases per 1,000 patients over 5 years (0.4 per 1,000 per year) in low-risk individuals 1
• A 2019 meta-analysis of 134,446 patients found a 37% relative risk increase (RR 1.37,95% CI 1.13-1.66), translating to 2 additional ICH events per 1,000 people 2
• The absolute risk remains very low at 0.2% over several years of follow-up 2

Secondary Prevention (High-Risk Cardiovascular Patients)

• In patients at high risk for cardiovascular events, aspirin causes less than 1 additional ICH per 1,000 patients per year 1
• Among moderate-risk participants (1% annual coronary event risk), aspirin was associated with 5 additional hemorrhagic strokes per 1,000 over 5 years (1 per 1,000 per year) 1
• Patients with cerebrovascular disease have a somewhat higher risk than other high-risk cardiovascular populations 1

Acute Stroke Setting

• In the International Stroke Trial, aspirin 300 mg daily caused a small 0.1% absolute increase in ICH incidence during the 14-day treatment period 1
• The Chinese Acute Stroke Trial showed a modest but non-significant increase in ICH risk with aspirin 160 mg daily 1

Risk Factors for Higher ICH Rates

Patient Demographics

• Asian race/ethnicity: Significantly heightened risk of intracerebral hemorrhage with aspirin 2
• Low body mass index: Associated with increased ICH risk on aspirin 2
• Age ≥60 years or older: Higher bleeding risk, particularly in hypertensive women 1
• Hypertensive women: Increased risk of subarachnoid hemorrhage, especially with high-frequency aspirin use (≥15 tablets per week) 1

Concurrent Medications

• Aspirin plus other anticoagulants/antiplatelets: Risk of delayed hemorrhage is 3.8 times higher when aspirin is combined with other AC/AP agents compared to AC/AP alone 3
• Dual antiplatelet therapy: Increased ICH risk in several clinical trials, particularly in patients with prior stroke 1

Dose-Related Considerations

• High-frequency use (≥15 tablets per week) increases subarachnoid hemorrhage risk 1
• Low-dose aspirin (75-100 mg daily) in UK observational data showed no increased risk of any ICB type (RR 0.98,95% CI 0.84-1.13) 4

Type-Specific ICH Risks

Subdural/Extradural Hemorrhage

• Greatest relative risk increase with aspirin (RR 1.53,95% CI 1.08-2.18) 2
• In trauma patients >60 years on low-dose aspirin, no statistically significant increase in traumatic ICH (24.5% vs 25.6% in controls) 5

Intracerebral Hemorrhage

• Moderate relative risk increase in primary prevention populations 2
• No increased risk in UK observational data (RR 0.98,95% CI 0.80-1.20) 4

Subarachnoid Hemorrhage

• Decreased risk with ≥1 year of low-dose aspirin use (RR 0.69,95% CI 0.50-0.94) 4
• High-frequency aspirin use increases risk in older or hypertensive women 1

Clinical Context: Trauma Patients

Minor Head Trauma

• In patients >60 years with mild-to-moderate head injury (GCS 13-15), low-dose aspirin does not increase surgically relevant bleeding (4.5% required surgery in aspirin group vs 4.1% in controls) 5
• Patients on low-dose aspirin with BIG 1-grade injuries had 2.2% rate of neurosurgery/mortality, significantly lower than BIG 3 patients at 27% 6

Delayed Hemorrhage Risk

• Mean time to delayed hemorrhage is 20 hours in trauma patients on antiplatelet agents 3
• Overall incidence of delayed hemorrhage is 1.91% with 0.3% mortality 3
• Risk is significantly higher with concurrent aspirin plus other AC/AP agents 3

Important Caveats

• The FDA warns that aspirin may cause severe stomach bleeding, with higher risk in patients ≥60 years old 7
• Hemorrhagic transformation of ischemic infarction shows a small but significant increase with early aspirin administration 1
• In patients with prior stroke or TIA, the risk-benefit calculation shifts, and caution is warranted when adding aspirin to other antithrombotic agents 1
• Warfarin or traditional antiplatelet agents show significantly higher delayed hemorrhage rates (3.2%) compared to DOACs (0.9%) when combined with aspirin 3