Low-dose aspirin use was associated with an overall increased risk of intracranial hemorrhage in individuals without symptomatic cardiovascular disease (CVD), and was also linked to an increased risk of intracerebral hemorrhage in individuals of Asian race/ethnicity or those with a low body mass index (BMI), in a recent study published in JAMA Neurology. “Because the benefits of low-dose aspirin for primary prevention of cardiovascular events are not well established, and the outcomes of intracranial hemorrhage are often catastrophic, these findings suggest caution regarding using low-dose aspirin in individuals without symptomatic cardiovascular disease,” the authors wrote. Risks of aspirin Daily low-dose aspirin has long been prescribed for the prevention of ischemic stroke and myocardial infarction (MI). But how safe is it really? Although aspirin is a cost-effective and readily available drug that can minimize the risk of blood clotting, it can also prolong bleeding time and increase the risk of hemorrhage. Of all potential bleeding events, intracranial hemorrhage represents a special concern due to its association with poor life-long health outcomes and risk of mortality. While this risk is outweighed by the drug’s potential to curb stroke and MI in most patients, researchers have questioned whether it should be used in people without history or symptoms of heart disease. For this study, researchers from Taiwan and the University of California sought to determine whether the risk of intracranial hemorrhage outweighs the benefit of low-dose (≤ 100 mg) aspirin therapy in asymptomatic individuals. They conducted a systematic review and meta-analysis of 13 randomized controlled trials representing nearly 135,000 patients. Eligible studies included those in which participants who received low-dose aspirin therapy were compared with healthy volunteers (control group). Increased bleeding Overall, the investigators noted an increased risk of general intracranial hemorrhage in individuals without symptomatic CVD compared with control participants (RR 1.37; 95% CI 1.13-1.66), with the greatest risk increase for subdural and extradural hemorrhages (RR 1.53; 95% CI 1.08-2.18), and the lowest risk increase for subarachnoid hemorrhage (RR 1.13; 95% CI 0.70-1.83). While the reasons for these differences remain unknown, this study is one of the first to address the specific subtypes of intracranial hemorrhage associated with aspirin use. “Given that the many individuals in the general population have a very low risk of atherosclerotic cardiovascular events, if low-dose aspirin is given universally, adverse outcomes from intracranial hemorrhage may outweigh the beneficial effects of low-dose aspirin,” the authors concluded. In population subgroup analyses, the researchers also identified a significantly magnified risk of intracerebral hemorrhage in Asian populations and in people with mean BMI of less than 25. Interestingly, the former is in line with findings from other epidemiological studies, in which the ratio of hemorrhagic stroke to ischemic stroke is higher in Asian vs non-Asian populations. According to the researchers, this may be due to the higher incidence of uncontrolled blood pressure and smoking in the Asian population as well as increased consumption of fish in the Asian diet—which is associated with increased ingestion of omega-3 fatty acids and antithrombotic effects. The correlation of BMI is also consistent with studies, suggesting that low weight and low BMI are predisposing factors to a higher ratio of hemorrhagic to ischemic stroke. Ultimately, low-dose aspirin therapy should not be administered universally to patients without CVD symptoms, according to these study findings. Because hemorrhaging episodes are associated with greater risks of mortality and life-long disability vs ischemic events (ie, stroke or MI), the threat of hemorrhage overshadows the possible benefits of avoiding ischemic events, the researchers concluded. In previous research, investigators estimated that for each intracerebral hemorrhaging event, there is an equivalent loss of 6.2 quality-adjusted-life years. So, in the game of risk-reward analysis, low-dose aspirin therapy is not a win-win for all patient populations. Source
