Cohort Study: Do Anticonvulsants Interfere with DOAC Therapy?

Background: Anticonvulsants vary in their theoretical propensity to interact with direct oral anticoagulants (DOACs). Coprescription may reduce DOAC efficacy and increase risk of thromboembolism.

Objectives: To evaluate the risk of clinical outcomes – thromboembolism, major bleeding, and death – among patients who were receiving a DOAC and newly treated with an interacting anticonvulsant relative to those newly treated with a non-interacting anticonvulsant.

Methods: We undertook 3 cohort studies using administrative health care data for Ontarians aged ≥66 years who were using a DOAC and newly prescribed 1 of 3 groups of anticonvulsants with declining theoretic propensity for interaction: group 1 (strongly interacting); group 2 (mildly interacting); and group 3 (potentially interacting). Each cohort was compared with a reference group of patients who were newly coprescribed a DOAC with a presumed noninteracting anticonvulsant. The primary outcome was hospitalization for thromboembolism. Secondary outcomes were major bleeding, death, and a composite of thromboembolism or death. Analysis was by propensity score inverse probability of treatment weighted competing risk Fine-Gray regression models.

Results: We studied 17 325 patients: 878 in group 1; 313 in group 2; 943 in group 3; and 15 191 in the reference group. After inverse probability of treatment weighted, we did not observe an association with thromboembolism or major bleeding in groups 1 to 3. The Cox proportional hazards ratio for death in those prescribed group 1 anticonvulsants was 2.21 (95% CI, 1.77-2.75).

Conclusion: In patients using a DOAC and newly prescribed a group 1, 2, or 3 anticonvulsant, we did not observe an increased risk of thromboembolism. In patients newly coprescribed a DOAC with a group 1 anticonvulsant, the observed increased risk of death is likely due to residual confounding.