Abstract
Background The U.S. Food and Drug Administration (FDA) Adverse Event (AE) Reporting System (FAERS)
is a global passive surveillance repository requiring mandatory updates by pharmaceutical
manufacturers. Oral antiplatelet agents (OAAs) including aspirin (acetylsalicylic
acid [ASA]) are broadly used to prevent thrombosis, at the expense of extra bleeding
risks. However, the OAA filing quality and their comparative patterns in FAERS are
unknown. We assessed completeness of original annual FAERS reports for OAA with special
attention on ASA.
Methods We extracted AE cases co-reported with OAA including ASA, clopidogrel, prasugrel,
ticagrelor, vorapaxar, or their combination. The 2015 FAERS cases were examined based
on OAA distribution, suspected causative role, missing gender or age, and most common
AEs after ASA.
Results A total of 1,187,729 reports qualified the inclusion criteria. The majority (n = 1,121,989) of the reports contain no reference of OAA, while 65,730 reports contain
reference of at least one OAA, including 47,900 ASA cases. Therapy with ASA was heavily
(>50%) underreported when used with prasugrel or ticagrelor, but still dominant (72.8%)
among OAAs, followed by clopidogrel (18.7%), prasugrel (4.1%), ticagrelor (3.6%),
and anecdotal vorapaxar (0.05%). Despite current recommendations, some (0.73%) reports
contain multi-OAAs. The primary role of ASA in AE reporting was seldom (<1%), followed
by clopidogrel (2.9%), prasugrel (3.7%), and highest for ticagrelor (9.3%). Missing
gender after OAA was not common (<10%), but age was missing in approximately 25% of
reports. Bleeding was the most frequent AE associated with ASA.
Conclusion The quality of reporting for OAA in general and ASA in particular can be improved
by stricter FDA rules, better surveillance, and enforcements. Heavy ASA underreporting
during dual antiplatelet therapy and missed demographic variables challenge outcome
research capacities for establishing drug interactions in FAERS.
Keywords
aspirin - antiplatelet agents - adverse events - safety - registry
