Study Finds Low Incidence of Intracranial Bleeding With Preventive Low-Dose Aspirin

The protective effect of low-dose aspirin against ischemic cardiovascular (CV) events and colorectal cancer (CRC) appears to outweigh the risks of major bleeding, including intracranial bleeding (ICB), according to results from a population-based study published in the Journal of Thrombosis and Haemostasis. However, factors such as age, sex, and indication for low-dose aspirin prescription were associated with different ICB incidence rates.

Using data from The Health Improvement Network (THIN), the United Kingdom’s primary-care database, Lucía Cea Soriano, from the Department of Preventive Medicine and Public Health at the Complutense University of Madrid in Spain, and co-authors estimated an ICB incidence of 0.8 per 100 person-years among new users of low-dose aspirin.

“There is increasing interest in the balance of overall benefits and risks of low-dose aspirin as a preventive agent, for both CV [disease (CVD)] and CRC prevention,” the authors wrote. “[Our] results provide valuable measures for incorporation into benefit-risk assessments of low-dose aspirin use in [both settings].”

To estimate the incidence of ICB, the researchers selected adult patients enrolled in THIN who had a registered primary-care physician for at least two years and had at least one clinical visit within three years of enrollment. Included patients had never been prescribed low-dose aspirin (75 or 300 mg) for primary or secondary prevention of CV events or CRC. Patients with a diagnosis of cancer, alcohol abuse, coagulopathies, esophageal varices, or chronic liver disease at any time prior to study entry were excluded.

The researchers identified 199,079 patients (mean age = 63.9 years). Beginning with the first date of low-dose aspirin prescription, patients were followed for as long as 14 years (median = 5.58 years).

During follow-up, 881 patients had confirmed ICB events: 407 intracerebral hemorrhages (ICHs), 283 subdural hematomas (SDHs), and 191 subarachnoid hemorrhages (SAHs).

The overall ICB incidence rate was 0.8 per 100 person-years (95% CI 0.07-0.08), and incidence rates for each bleeding type were:

  • 0.04 for ICH (95% CI 0.03-0.04)
  • 0.03 for SDH (95% CI 0.02-0.03)
  • 0.02 for SAH (95% CI 0.01-0.02)

When the investigators restricted their cohort to the 58,551 patients with continuous low-dose aspirin use throughout follow-up, the ICB incidence rate appeared to be higher (0.13 per 100 person-years; 95% CI 0.11-0.14), but p values were not reported.

In the entire cohort, 21 percent of all ICB events were fatal (n=185/881), meaning a patient died within 30 days of recorded ICB diagnosis. The median age at the time of ICB-related death was 74 years, and ICB-related mortality rates according to ICB location were:

  • 27.3% (n=111/407) for ICH
  • 9.9% (n=28/283) for SDH
  • 24.1% (n=46/191) for SAH

The rates were lower than reported in previous population-based studies, in which ICB-related fatality rates ranged from 28.7 to 42.0 percent.

Trauma accounted for 28.4 percent (n=250) of all ICB events, including 11.8 percent (n=48) of ICH, 59.7 percent (n=169) of SDH, and 17.3 percent (n=33) of SAH occurrences. The overall incidence rates of non-trauma- and trauma-related ICBs were 0.05 (95% CI 0.05-0.06) and 0.02 (95% CI 0.02-0.02) per 100 person-years, respectively.

The overall incidence rate was similar between men and women, but women had higher rates of ICH and SAH events (0.038 vs. 0.033 and 0.019 vs. 0.014 per 100 person-years, respectively; p values not provided). The incidence rates of ICH and SDH increased notably with age, whereas SAH rates remained “broadly similar, increasing only slightly with age,” the authors wrote.

The ICB incidence was also higher among those receiving low-dose aspirin for secondary CVD prevention (0.09 per 100 person-years; 95% CI 0.08-0.01) than among those receiving it for primary CVD prevention (0.07 per 100 person-years; 95% CI 0.06-0.07; p values not provided).

“The decision to prescribe low-dose aspirin for CVD prevention is dependent on several, largely age-dependent factors, including whether the patient has previously experienced, or is at high risk of experiencing, an ischemic CV event, and the risk of major bleeding events,” the authors concluded. “Even taking into account the risk of major bleeding associated with the long-term use of low-dose aspirin, the net clinical benefit is clearly in favor of low-dose aspirin use in the secondary-prevention setting.”

The possibility that patients discontinued low-dose aspirin during follow-up was a potential limitation of the study, as was its retrospective design and use of population-level data. The study was funded by Bayer AG, a manufacturer of aspirin.

Contributing authors report research funding from Bayer AG.


Cea Soriano L, Gaist D, Soriano-Gabarró M, et al. Incidence of intracranial bleeds in new users of low-dose aspirin: a cohort study using The Health Improvement Network. J Thromb Haemost. 2017;15:1055-64.