The Benefit and Safety of Aspirin for Primary Prevention of Ischemic Stroke: A Meta-Analysis of Randomized Trials

Abstract

Background: Although aspirin is effective in the secondary prevention of stroke among men and women, its use in primary prevention remains controversial. We conducted a meta-analysis of randomized trials to evaluate the benefit and safety of aspirin for the primary prevention of ischemic stroke.Methods: We searched three electronic databases (Medline, the Cochrane Central Register of Controlled Trials, and Embase) for articles published before August 1st, 2016. Randomized trials reporting the effect of aspirin on the primary prevention of ischemic stroke and its side effects (hemorrhagic stroke and severe gastrointestinal bleeding) were included. We used a fixed-effect model to quantify the effect of aspirin on the primary prevention of stroke when the heterogeneity was low, or else applied the random-effect model.Results: Fourteen randomized trials were included. Overall, aspirin use was associated with a decreased risk of ischemic stroke compared with non-aspirin use (OR: 0.83, 95% CI: 0.74–0.93, P = 0.45). In subgroup analyses, the effect of aspirin on ischemic stroke in apparently healthy adults remained significant (OR: 0.83, 95% confidence interval: 0.74–0.94, I2 = 22%, P = 0.28); while in patients with cardiovascular diseases there was no difference in the risk of ischemic stroke between aspirin and non-aspirin groups (OR: 0.75, 95% confidence interval: 0.44–1.29, P = 0.46). As for adverse effects, the prophylactic use of aspirin potentially increased the risk of serious bleeding events in a population of apparently healthy individuals and in patients with previous cardiovascular diseases.Conclusion: This meta-analysis of randomized trials indicated that both the apparently healthy adults and patients with cardiovascular diseases will derive little protective benefit from aspirin considering the increased risk of severe bleeding events.

Harms and Benefits of Using Aspirin for Primary Prevention of Cardiovascular Disease: A Narrative Overview

“…11 Regarding cardiovascular disease, the most favorable impact could be noticed for MACE, with most meta-analyses 14,16,17,19 (but not the study of the ASPREE Investigator Group), 12 reporting a decreased risk in people receiving aspirin. However, this apparent benefit does not translate into tangible benefits on reducing the risk of cardiovascular mortality, 12,15,17,19 or ischemic stroke, 12,15,17,19 which appears constantly unaffected by the use of aspirin in all published studies, except in the meta-analysis of Lei et al 18 A modest favorable effect of aspirin in decreasing the risk of myocardial infarction was noted in two meta-analyses, 15,17 but not in other two meta-analyses, 14,19 nor in the randomized trial of the ASPREE Investigator Group. 12 The potential impact of aspirin on future cancer risk also appears largely heterogeneous, wherein one meta-analysis reported a lower risk, 25 other meta-analyses failed to report a significant effect, 16,22,23 while the randomized trial of the ASPREE Investigator Group even reported a 31% increased risk of developing malignancies, especially colorectal cancer (►Table 2).…”

“…16,22,23 Unlike these endpoints, the bleeding risk of patients receiving aspirin for primary prevention of cardiovascular disease was found to be consistently increased in all published studies. 12,14,17,22 In only one meta-analysis was aspirin treatment not associated with intracranial bleeding, 22 whereas such risk was found to be significantly increased in the remaining reports, 14,17,18 as well as in the randomized trial of the ASPREE Investigator Group. 12 Regarding aspirin dosages, no major benefits (or harms) could be observed in studies analyzing the effect of low-dose aspirin (►Table 3).…”

“…In the meta-analysis of Lei et al, 18 aspirin use was found to considerably enhance the risk of hemorrhagic stroke (OR, 1.32; 95% CI, 1.04-1.68), and this risk also appeared marginally higher when the analysis was limited to apparently healthy individuals (OR, 1.35; 95% CI, 1.05-1.75).…”

“…Unlike these findings, Lei et al performed a meta-analysis of 14 randomized trials exploring the effects of aspirin in primary prevention of ischemic stroke in people with or without cardiovascular risk factors. 18 Overall, aspirin was found to be effective for lowering the risk of ischemic stroke (odds ratio [OR], 0.83; 95% CI, 0.74-0.93), and this benefit remained virtually identical when the analysis was limited to apparently healthy individuals (OR, 0.83; 95% CI, 0.74-0.94).…”

Late-onset seizures: a subclinical cerebrovascular disorder?

“…To further complicate matters, one has to consider the risks associated with aspirin used as primary prevention of cerebrovascular disease, e.g. the increased risk of cerebral bleeding which may outweigh benefits of reduction in ischemic stroke [20].…”