BACKGROUND: Oral anticoagulants are superior to antiplatelet agents for preventing cardioembolic stroke but concerns about increased risk of intracranial hemorrhage limit their use. Although rivaroxaban demonstrably increases intracranial bleeding risk compared with aspirin, the comparative risk of intracranial hemorrhage with apixaban versus aspirin remains uncertain. We aimed to clarify this risk through a meta-analysis of randomized controlled trials.
METHODS: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for randomized controlled trials comparing apixaban with aspirin for ischemic stroke prevention. Studies were excluded if no intracranial hemorrhage events were reported in either arm. In the primary analysis, we used the Mantel-Haenszel method to meta-analyze the relative risk of intracranial hemorrhage with apixaban versus aspirin therapy. We conducted sensitivity analyses to examine the strength of these findings and to examine the secondary outcome of hemorrhagic stroke (which excludes epidural and subdural hematomas).
RESULTS: Three randomized controlled trials met our inclusion criteria, comprising a total of 10 626 patients and 74 incident intracranial hemorrhage events. In the pooled analysis, the relative risk of intracranial hemorrhage with apixaban versus aspirin therapy was 0.67 ([95% CI, 0.43-1.08]; P=0.10). These findings were consistent in sensitivity analyses utilizing alternative statistical estimators, in analyses limited to primary prevention trials, and in analyses utilizing the outcome of hemorrhagic stroke (relative risk, 0.72 [95% CI, 0.39-1.31]; P=0.28).
CONCLUSIONS: In randomized controlled trials evaluating ischemic stroke prevention, apixaban demonstrated a safety profile comparable-and potentially superior-to aspirin with respect to intracranial hemorrhage risk. These findings warrant a reconsideration of clinical practices that favor aspirin over apixaban, because of the concerns about intracranial hemorrhage risk.
| Specialty | Score |
|---|---|
| Hospital Doctor/Hospitalists | |
| Internal Medicine | |
| Hematology | |
| Hemostasis and Thrombosis | |
| Neurology | Coming Soon... |
Although focused on thrombosis providers, this article highlights (again) that there are significant misconceptions about the safety of aspirin compared with anticoagulants. Hopefully, this will act to dispel the perception that ASA is "harmless."
As both aspirin and apixaban are extremely common medications and the concerns identified here are common, this paper is critical knowledge for the practicing internist and hospitalist in modern medical care.
This meta-analysis is consistent with previous trial results and does not substantially change the perception of the safety of apixaban compared with aspirin. Factor Xa inhibitors like apixaban have a substantially lower risk for intracranial hemorrhage than warfarin. In AVERROES that was conducted in an AF population, no significant difference in the risk for ICH was noted between aspirin and apixaban. This study level meta-analysis combines AVERROES with ARTESIA and ARCADIA - including primary and secondary prevention populations. Correction for other factors that may determine risk such as age and hypertension isn't possible with study level data. The absolute number of events is small and, as a consequence, the confidence intervals are wide enough to include the possibility of a higher or lower risk for hemorrhage with apixaban than aspirin.
This meta-analysis provides compelling evidence that apixaban is at least as safe as aspirin regarding intracranial hemorrhage risk while offering superior stroke prevention in patients with AF. The findings challenge the common practice of favoring aspirin due to bleeding concerns.
, McMaster University