Saturday, July 13, 2024

Study Reveals Impact of Antiseizure Medications on Anticoagulant Efficacy and Safety in Adults with Atrial Fibrillation and Epilepsy

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The concurrent prescription of direct-acting oral anticoagulants (DOACs) and antiseizure medications (ASMs) in adults with atrial fibrillation (AF) and epilepsy has raised concerns regarding potential pharmacokinetic interactions. These interactions can influence the absorption and metabolism of DOACs, possibly affecting their therapeutic efficacy and safety profiles. A recent cohort study delved into this issue, examining the rates of thromboembolic and major bleeding events in this patient population.

Design and Participants

Conducted using the Clinformatics Data Mart database, the study encompassed a decade’s worth of data (October 2010 to September 2021) from a nationally representative sample of U.S. adults diagnosed with both AF and epilepsy. Researchers focused on episodes where DOACs were coadministered with enzyme-inducing (EI) ASMs (exposed group) or non-EI ASMs (referent group). The objective was to compare the incidence of thromboembolic and major bleeding events between these two cohorts.

Findings and Implications

The analysis included 14,078 episodes for thromboembolic assessment and 14,158 episodes for bleeding assessment, with a median patient age of 74 years. The primary outcome showed an incidence rate of 88.5 per 1000 person-years for thromboembolic events, while major bleeding events had an incidence rate of 68.3 per 1000 person-years. Importantly, the use of EI ASMs with DOACs did not significantly alter the risk of thromboembolic events (AHR, 1.10; 95% CI, 0.82-1.46) compared to non-EI ASMs. However, EI ASMs were associated with a notable reduction in major bleeding risk (AHR, 0.63; 95% CI, 0.44-0.89).

From a market access perspective, these findings could influence prescription practices and drug formulary decisions. Health care providers may need to consider the type of ASM when prescribing DOACs to optimize patient outcomes and minimize adverse events.

Concrete Inferences

Based on the study’s results, several valuable insights emerge:

  • The absence of increased thromboembolic risk with EI ASMs suggests these medications do not compromise the efficacy of DOACs.
  • The reduced bleeding risk associated with EI ASMs indicates potential benefits in safety profiles, warranting further exploration of pharmacokinetic interactions.
  • These findings could shape clinical guidelines and influence drug formulary decisions in the management of patients with AF and epilepsy.

The study underscores the importance of understanding drug interactions in complex patient populations. As DOACs and ASMs are frequently co-prescribed, awareness of these interactions can guide clinicians in making informed decisions to enhance patient care. Further research is essential to elucidate the mechanisms behind these observations and to refine therapeutic strategies.

Original Article:

JAMA Neurol. 2024 Jul 8. doi: 10.1001/jamaneurol.2024.2057. Online ahead of print.


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IMPORTANCE: Direct-acting oral anticoagulants (DOACs) are commonly prescribed with antiseizure medications (ASMs) due to concurrency of and the association between atrial fibrillation (AF) and epilepsy. However, enzyme-inducing (EI) ASMs may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk.

OBJECTIVE: To assess the rates of thromboembolic and major bleeding events in adults with AF and epilepsy dispensed DOACs and EI ASMs vs DOACs with non-EI ASMs.

DESIGN, SETTING, AND PARTICIPANTS: This active-comparator, new-user cohort study included US health care data from the Clinformatics Data Mart database from October 2010 to September 2021 for a nationally representative population of adults with AF and epilepsy.

EXPOSURE: Evaluations included episodes of contiguous coadministration of DOACs for AF with EI ASMs (exposed) or non-EI ASMs (referent) for epilepsy.

MAIN OUTCOMES AND MEASURES: Thromboembolic events (primary outcome) and major bleeding events (secondary outcome) were identified based on a series of validated, diagnosis-based coding algorithms. Data-adaptive, high-dimensional propensity score matching was used to control for observed confounders and proxies for unobserved confounders. Adjusted hazard ratios (AHRs) were estimated using Cox proportional hazards regression models with robust variance estimators to account for clustering within matched pairs.

RESULTS: This study included 14 078 episodes (median age, 74 [IQR, 67-81]; 52.4% female) and 14 158 episodes (median age, 74 [IQR, 67-81]; 52.4% female) of incident DOAC and ASM use that met eligibility criteria for assessment of thromboembolic and major bleeding outcomes, respectively. Incidence was 88.5 per 1000 person-years for thromboembolic events and 68.3 per 1000 person-years for bleeding events. Compared with use of non-EI ASMs, use of EI ASMs with DOACs was not associated with a difference in risk of thromboembolic events (AHR, 1.10; 95% CI, 0.82-1.46) but was associated with a reduction in risk of major bleeding events (AHR, 0.63; 95% CI, 0.44-0.89).

CONCLUSIONS AND RELEVANCE: In this cohort study, EI ASMs were not associated with alteration in DOAC efficacy. Further research is needed on the reduction in bleeding risk associated with EI ASMs, as this may suggest that pharmacokinetic interactions are associated with lowering DOAC levels without negating therapeutic effects.

PMID:38976246 | DOI:10.1001/jamaneurol.2024.2057

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