Association of direct oral anticoagulant-anticonvulsant co-prescription 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). Co-prescription may reduce DOAC efficacy and increase risk of thromboembolism.

Methods — We undertook three cohort studies using administrative healthcare data for Ontarians aged 66 years and older who were using a DOAC and newly prescribed one of three 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 co-prescribed a DOAC with a presumed non-interacting 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 (IPTW) 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 IPTW, we did not observe an association with thromboembolism or major bleeding in groups 1-3. The Cox proportional HR 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 co-prescribed a DOAC with a group 1 anticonvulsant, the observed increased risk of death is likely due to residual confounding.