Abstracts

Rationale: Comorbidity and causative links between thrombogenic conditions and epilepsy yield frequent indications for co-prescription of oral anticoagulants (OACs) with antiepileptic drugs (AEDs). There are well-established interactions between enzyme-inducing AEDs (EI-AEDs) and the previous mainstay of oral anticoagulation, warfarin, as well as some preliminary evidence suggesting possible interactions with the newer direct OACs (DOACs). In order to contextualize the scale of co-prescriptions and corresponding impacts of these potential interactions, we sought to enumerate real-world clinical patterns of concurrent prescriptions for OACs with EI-AEDs among people with epilepsy (PWE). Methods: We used OptumInsight ClinformaticsTM Data Mart Claims Database, a multi-payer claims database with over 60 million individuals, to measure concurrent prescription claims for OACs and AEDs among PWE from January 1, 2010-Decemeber 31, 2016.  We identified prevalent epilepsy diagnoses by a validated ICD-9/10 code algorithm.  Drugs dispensed during the same 3-month period were regarded as concurrently prescribed.  We specifically assessed for PWE on 1 or more EI-AEDs (carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate), as well as those on only commonly-used AEDs, considered unlikely to interact with the OACs (lacosamide, lamotrigine, and levetiracetam).  The OACs included warfarin, as well as those DOACs that received regulatory approval during the study time frame (dabigatran, rivaroxaban, apixaban, and edoxaban). The chi-squared test was used to evaluate for differences in annual co-prescribing, with linearity of trends assessed using the Cochran-Armitage test.  Results: Among the 71,561 PWE dispensed the studied AEDs in 2016, 5,679 (7.94%) had concurrent prescriptions for OACs, representing a substantial increase from the 5.48% (2,090/38,167) of PWE with co-prescriptions in 2010 (p<0.0001).  An increasing yearly trend in OAC co-prescription was seen among PWE on 1 or more EI-AEDs (p<0.0001), as well as those on only non-interacting AEDs (p<0.0001).  Figure 1 demonstrates the rapid uptake of DOAC use in PWE, including those on EI-AEDs. Conversely, warfarin co-prescriptions were found to decrease following peak use in 2011 among those on EI-AEDs and 2013 among those on only non-interacting AEDs.  In 2016, rivaroxaban was the most commonly used DOAC in these populations, with prescriptions in 1.48% (514/34,704) of those on EI-AEDs and 1.82% (732/40,254) of those on only non-interacting AEDs. Conclusions: The prevalence of co-prescriptions for OACs with AEDs from 2010-2016 in PWE was substantial and increased yearly, including among those on EI-AEDs. These findings highlight the clinical significance of advancing understanding of interactions between EI-AEDs and OACs, given their potential impact on as much as 7.17% of PWE. In particular, further research into proposed interactions with DOACs appears warranted in light of rapid uptake of this form of anticoagulation within the population with epilepsy. Funding: No funding