Objective  To mine and analyze signals of ischemic stroke (IS) related to drugs, comprehensively summarize the potential risk drugs, and to provide a reference for safe clinical medication.

Methods  IS reports from January 2004 to June 2024 in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database were retrieved. The relationship between specific drugs and IS was assessed using the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) methodologies. In addition, time to onset and patient outcomes were also analyzed.

Results  A total of 21,497,699 ADE reports were retrieved, among which 74,046 cases were identified as IS reports based on the preferred terms search. A total of 77 IS signaling drugs were screened, of which there were 32 drugs with ≥30 reports, and Andexanet alfa was the drug with the strongest IS signal (ROR=52.58). The median time of drug-associated IS occurrence was 166 days, with ranibizumab-associated IS occurring the earliest (median time of 0 day) and rosiglitazone-associated IS occurring the latest (median time of 1,282 days). Andexanet alfa (31.33%) and three other drugs had higher proportions of mortality.

Conclusion  Drugs with potentially high signals of IS, rapid onset of IS, and elevated mortality risk can serve as a warning to help clinicians in managing drug-related IS and selecting more appropriate alternative drugs for populations at high risk of stroke, thereby reducing stroke morbidity and mortality.

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