Increased Risk of Intracranial Hemorrhage when Aspirin Is Combined with Warfarin: A Meta-Analysis and Hypothesis

Background: Oral anticoagulation with vitamin K antagonists increases the risk of intracranial hemorrhage; whether addition of aspirin to oral anticoagulation augments this risk is unclear. Methods: Meta-analysis of randomized clinical trials in which aspirin was added to oral anticoagulants. Results: Six randomized clinical trials were identified, including a total of 3,874 participants. Use of aspirin with oral anticoagulants was associated with more than double the frequency of intracranial hemorrhage (relative risk = 2.4, 95% CI = 1.2–4.8, p = 0.02). Conclusion: We hypothesize that aspirin when added to oral vitamin K antagonists may increase the risk of intracranial hemorrhage, but this observation requires confirmation. The magnitude of this effect is uncertain, and the clinical importance is likely different for different patient populations.

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