Low-Dose Aspirin Use Associated With Risk for Intracranial Hemorrhage

older woman in inpatient bed
Low-dose aspirin use for primary prevention of cardiovascular events in people without symptomatic cardiovascular disease was associated with an increased risk for intracranial hemorrhage.

Low-dose aspirin usage in primary prevention of cardiovascular events without symptomatic cardiovascular disease is associated with increased risk for intracranial hemorrhage, particularly in Asian populations and in patients with lower body mass index (BMI), according to a study published in JAMA Neurology.

In this systematic review and meta-analysis, investigators searched for published results of studies involving humans and clinical trials through October 30, 2018, on PubMed, Embase, and the Cochrane Central Register of Controlled Trials. Investigators also searched the clinical trial registry online. Inclusion criteria were studies with randomized clinical trials, comparison between aspirin and placebo or aspirin and no aspirin, at least 1 end point related to hemorrhage reported, aspirin dosage ≤100 mg once daily, and treatment duration for ≥6 months.

Related Articles

A total of 13 randomized clinical trials were identified that compared aspirin and control in individuals enrolled in the studies (N=134,446). The mean age of patients ranged from 42.9 to 74.0 years. Low-dose aspirin use compared with control was associated with increased risk for any intracranial hemorrhage in 8 trials (0.63% vs 0.46%; relative risk [RR], 1.37; 95% CI, 1.13-1.66).

Compared with control, low-dose aspirin would be associated with an additional 2 intracranial hemorrhages in 1000 people. Pooling results from random-effects models, low-dose aspirin compared with control showed a strong but nonsignificant association with a higher risk for intracerebral hemorrhage in 10 trials (0.3% vs 0.24%; RR, 1.23; 95% CI, 0.98-1.54). Low-dose aspirin compared with control was associated with increased risk for subdural or extradural hemorrhage in 4 trials (0.31% vs 0.2%; RR 1.53; 95% CI, 1.08-2.18). Compared with control, low-dose aspirin had a similar risk for subarachnoid hemorrhage in 5 trials (0.14% vs 0.12%; RR, 1.13; 95% CI, 0.70-1.83; P =.83 for heterogeneity).

Subgroup analysis indicated that low-dose aspirin was associated with a greater level of increased risk for intracranial hemorrhage in Asian race/ethnicity with a mean BMI <25.

One limitation of this study is that literature searches for the meta-analysis may have been biased and failed to identify all relevant trials. Investigators performed thorough searches across multiple literature and clinical trial databases and to reduce these risks. Additionally, because of the participant-level meta-analysis design, only univariate associations of baseline features with outcomes were examined.

The researchers indicated that the greatest risk increase was for subdural and extradural hemorrhage and the lowest risk increase for subarachnoid hemorrhage. Based on these findings, the investigators also suggested that clinicians should exercise caution when prescribing low-dose aspirin to individuals who do not have symptomatic cardiovascular disease.


Huang WY, Saver JL, Wu YL, Lin CJ, Lee M, Ovbiagele B. Frequency of intracranial hemorrhage with low-dose aspirin in individuals without symptomatic cardiovascular disease: a systematic review and meta-analysis [published online May 13, 2019]. JAMA Neurol. doi:10.1001/jamaneurol.2019.1120