Association of direct oral anticoagulant-anticonvulsant coprescription with clinical outcomes in older adults: a population-based cohort study.

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.