Physicians' Academy for Cardiovascular Education

Increased risk of intracranial hemorrhage with aspirine use in those without symptomatic CVD

Frequency of Intracranial Hemorrhage With Low-Dose Aspirin in Individuals Without Symptomatic Cardiovascular Disease - A Systematic Review and Meta-analysis

Literature - Huang W-Y, Saver JL, Wu Y-L, et al. - JAMA Neurol 2019; doi:10.1001/jamaneurol.2019.1120

Introduction and methods

Benefits of low-dose aspirin in prevention of myocardial infarction and ischemic stroke outweigh the harm of increased bleeding risk in a population with CVD. However, this benefit-risk balance is less clear for primary prevention of CVD, because in individuals without previous CVD the risk of CV events is lower and increased risk of bleeding may offset the benefit of aspirin [1-3].

A systematic review and meta-analysis were conducted to examine the association between aspirin use and risk of bleeding in those without symptomatic CVD for the following reasons. Intracranial hemorrhage is strongly associated with high mortality risk and poor outcomes [4,5]. Meta-analyses have shown conflicting results for risk of intracranial hemorrhage with use of aspirin for primary prevention of CVD [2,3,6-9]. In addition, specific subtypes of intracranial hemorrhage have not been investigated in previously published meta-analyses. And finally, there are new data from 3 recently published large trials showing controversial results [10-12].

PubMed, Embase, the Cochrane Central Register of Controlled Trials, and were searched from January 1966 to October 30, 2018. Inclusion criteria were: randomized clinical trial, comparison of aspirin with placebo or no aspirin, report of all intracranial hemorrhages, all hemorrhagic strokes, intracerebral hemorrhages, subdural or extradural hemorrhages, or subarachnoid hemorrhages, total participants and those with an endpoint were reported separately, aspirin dose ≤100 mg once daily, and treatment duration >6 months.

Main results


Results of a meta-analysis of 13 trials comprising 134,446 individuals showed that in people without symptomatic CVD, use of low-dose aspirin was associated with increased risk for any intracranial hemorrhage compared to control. More specific, risk of subdural or extradural hemorrhage was increased in those who took aspirin compared to control. Subgroup analyses showed that those of Asian race or BMI <25 had a higher risk of intracerebral hemorrhage when taking aspirin compared to control. The authors of this study suggest to be cautious when considering use of low-dose aspirin for primary prevention of CVD.


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