Low-Dose Aspirin and the Risk of Stroke and Intracerebral Bleeding in Healthy Older People

Abstract

ImportanceLow-dose aspirin has been widely used for primary and secondary prevention of stroke. The balance between potential reduction of ischemic stroke events and increased intracranial bleeding has not been established in older individuals.ObjectiveTo establish the risks of ischemic stroke and intracranial bleeding among healthy older people receiving daily low-dose aspirin.Design, Setting, and ParticipantsThis secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized, double-blind, placebo-controlled trial of daily low-dose aspirin was conducted among community-dwelling people living in Australia or the US. Participants were older adults free of symptomatic cardiovascular disease. Recruitment took place between 2010 and 2014, and participants were followed up for a median (IQR) of 4.7 (3.6-5.7) years. This analysis was completed from August 2021 to March 2023.InterventionsDaily 100-mg enteric-coated aspirin or matching placebo.Main Outcomes and MeasuresStroke and stroke etiology were predetermined secondary outcomes and are presented with a focus on prevention of initial stroke or intracranial bleeding event. Outcomes were assessed by review of medical records.ResultsAmong 19 114 older adults (10 782 females [56.4%]; median [IQR] age, 74 [71.6-77.7] years), 9525 individuals received aspirin and 9589 individuals received placebo. Aspirin did not produce a statistically significant reduction in the incidence of ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.71-1.11). However, a statistically significant increase in intracranial bleeding was observed among individuals assigned to aspirin (108 individuals [1.1%]) compared with those receiving placebo (79 individuals [0.8%]; HR, 1.38; 95% CI, 1.03-1.84). This occurred by an increase in a combination of subdural, extradural, and subarachnoid bleeding with aspirin compared with placebo (59 individuals [0.6%] vs 41 individuals [0.4%]; HR, 1.45; 95% CI, 0.98-2.16). Hemorrhagic stroke was recorded in 49 individuals (0.5%) assigned to aspirin compared with 37 individuals (0.4%) in the placebo group (HR, 1.33; 95% CI, 0.87-2.04).Conclusions and RelevanceThis study found a significant increase in intracranial bleeding with daily low-dose aspirin but no significant reduction of ischemic stroke. These findings may have particular relevance to older individuals prone to developing intracranial bleeding after head trauma.Trial RegistrationISRCTN.org Identifier: ISRCTN83772183

Increased Risk of Intracranial Hemorrhage in Older Patients Exposed to Multidrug Interactions Involving Warfarin

“…Cohort Inclusion Criteria provided the total number of patients with or without a prescription for two or more of the drugs (including Warfarin) of interest on the same day, regardless of ICH occurrence. The Inclusion Criteria also contained the total number of drugs a patient was prescribed in ranges of [1][2][3][4][5], [6][7][8][9][10], or [11][12][13][14][15]. Drugs were found through their respective RxNorm IDs.…”

“…To study the relationship between the prevalence of ICH and the number of drugs the patients were prescribed, the cohorts were divided into three groups based on the number of drugs prescribed: [1][2][3][4][5], [6][7][8][9][10], or [11][12][13][14][15] drugs.…”

“…Significant findings included that the Prevalence of ICH is significantly higher in patients exposed to three interacting drugs rather than just two (Figure 3). As the total number of drugs prescribed increases from [1][2][3][4][5] to [11][12][13][14][15], the prevalence of ICH across each combination subsequently increases as well. The results also depict an increase in prevalence when observing multidrug combinations (e.g.…”

“…To directly establish causation between a patient taking a certain combination of drugs and an increase in Intracranial Hemorrhage prevalence, a clinical study could be administered with a similar setup as that analyzed by Geoffrey C. Cloud [11] in which patients on certain drug combinations are observed and tracked for Intracranial Hemorrhage occurrences after drug administration.…”

Incorrect Data in Results and Figures

“…This article has been corrected. The corrections do not alter the results or conclusions of the study …”