(C27) Concomitant use of selective serotonin reuptake inhibitors with oral anticoagulants and the risk of major bleeding in patients with atrial fibrillation

Publication Number: 971

Background: Selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed antidepressants and are associated with a moderate increased risk of major bleeding. However, high-risk patients, such as those treated with oral anticoagulants (OACs), may be more susceptible.

Objectives: To assess whether concomitant use of SSRIs with OACs is associated with an increased risk of major bleeding compared with OACs alone.

Methods: We conducted a population-based cohort study with nested case-control sampling. We used the Clinical Practice Research Datalink, a large UK primary care database, to define a cohort of all adult patients with incident atrial fibrillation (AF) between 1998 and 2021 and a first prescription for an OAC (cohort entry). From this cohort, we identified cases as patients with a first hospitalization with a primary diagnosis for bleeding (index date). For each case, we used risk-set sampling to randomly select up to 30 controls, matched on age, sex, cohort entry date, and duration of follow-up. The index date for controls was the date resulting in the same duration of follow-up for cases and controls. Patients were considered exposed to SSRIs or OACs if a prescription covered or ended within 30 days of the index date. We used conditional logistic regression to estimate ORs for major bleeding associated with concomitant use of SSRIs and OACs, compared with OAC use alone. Finally, we assessed additive interaction between SSRIs and OACs by computing the relative excess risk due to interaction (RERI).

Results: The cohort included 331,105 patients with incident AF initiating OACs, from which 42,190 cases and 1,156,641 matched controls were identified. Concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding, compared with OAC use alone (OR 1.33, 95% CI 1.24-1.42). The association was similar for concomitant use of OACs and SSRIs with more (OR 1.34, 95% CI 1.22-1.47) and less (OR 1.31, 95% CI 1.19-1.43) potent serotonin reuptake inhibition, while being numerically higher for concomitant use of SSRIs with VKAs (OR 1.36, 95% CI 1.25-1.47) than with DOACs (OR 1.25, 95% CI 1.12-1.40). The association of concomitant SSRI and OAC use with intracranial hemorrhage (OR 1.56, 95% CI 1.32-1.85) was also numerically higher than with gastrointestinal (OR 1.38, 95% CI 1.24-1.53) or other bleeding (OR 1.23, 95% CI 1.12-1.36). Lastly, there may be limited additive interaction between SSRIs and OACs (RERI 0.10, 95% CI -0.07-0.27).

Conclusions: In patients with AF, concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding, compared with OAC use alone, both overall and in key patient subgroups. Thus, concomitant users should be closely monitored and may require adjustments to their treatment regimen.