1E-05 - Risk of Major Bleeding with Concomitant Use of Selective Serotonin Reuptake Inhibitors and Antithrombotics: a Nationwide Case-Case-Time-Control Study

Background: Selective serotonin reuptake inhibitors (SSRIs), a widely used antidepressants, are commonly co-administrated with antithrombotics (i.e., anticoagulants and antiplatelets) in older adults. Previous studies suggested that concomitant use of SSRIs and antithrombotics may increase the risk of major bleeding; however, this risk remains uncertain in Asian populations, who are more prone to bleeding.

Objectives: To evaluate the risk of major bleeding with the concomitant use of SSRIs and anticoagulants, SSRIs and antiplatelets, respectively

Methods: Using the nationwide healthcare data of South Korea between 2013 and 2023, we conducted a case-case-time-control (CCTC) study that included a case crossover design and a control crossover design consisting of future cases. Adults who were firstly hospitalized for major bleeding (including gastrointestinal, intracerebral, and other bleeding) and had at least one prescription of SSRIs and anticoagulants or antiplatelets were included. We selected future cases as patients whose cohort entry date (i.e., the earliest date on which an SSRI, anticoagulant, or antiplatelet was first prescribed) fell between 211 and 575 days from the date of outcome occurrence to improve comparability. We matched current cases to future cases by age and sex. For each participant, concomitant use of SSRIs and anticoagulants or antiplatelets during hazard periods (day −1 to −30 before first bleeding event) were compared with 5 reference periods (i.e., day −61 to −90, −91 to −120, −121 to −150, −151 to −180, and −181 to −210). Odds ratios (OR) with 95% confidence intervals (CI) were generated with conditional logistic regression models to evaluate the risk of major bleeding events with concomitant use of SSRIs and anticoagulants or antiplatelets.

Results: The analysis of SSRIs and anticoagulants included 110,540 current cases. Comparing the concomitant use vs. non-use, the adjusted OR for major bleeding was 1.63 (95% CI 1.39-1.91) in the case crossover and 1.52 (1.39-1.66) in control crossover, corresponding to CCTC adjusted OR of 1.07 (0.89-1.28). The analysis of SSRIs and antiplatelets included 105,464 current cases. Comparing the concomitant use vs. non-use, the adjusted OR was 1.21 (1.05-1.40) in the case crossover and 1.10 (0.93-1.30) in control crossover, corresponding to CCTC adjusted OR of 1.10 (0.88-1.38).

Conclusions: In this study of patients hospitalized for major bleeding, recent exposures to both SSRIs and antithrombotic agents were not associated with an increased risk of major bleeding after accounting for patient-level exposure time trends.