Background: Selective serotonin reuptake inhibitors (SSRIs) may increase the risk of major bleeding during vitamin K antagonist (VKA) (and other anticoagulant) treatment by decreasing platelet activation, increasing gastric acid secretion and decreasing VKA metabolism through cytochrome P450 2C9 (CYP2C9) inhibition.
Aims: To determine whether SSRIs cause major bleeding during VKA treatment and investigate the mechanisms behind this interaction.
Methods: Information on SSRI use and bleeding complications was obtained from patient records at the Anticoagulation Clinics of Leiden and Rotterdam of VKA initiators between 2006 and 2018. Conditional logistic regression and time-dependent Cox regression were used to estimate the effect of SSRIs on a high INR (≥ 5) within 2 months after SSRI initiation and on major bleeding during the entire period of SSRI use, respectively. SSRI use was stratified for (non)-CYP2C9 inhibitors. Participant consent was waived because the analysis used pre-existing, coded data.
Results: 58,918 patients were included, of whom 1504 were SSRI users. SSRI initiation versus non-use was associated with a 2.41-fold (95% confidence interval [CI] 2.01-2.89) increased risk for a high INR, which was 3.14-fold (95%CI 1.33-7.43) among CYP2C9 inhibiting SSRIs (table 1). SSRI use versus non-use was associated with a 1.22-fold (95% CI 0.99-1.50) increased risk for major bleeding in all SSRI users, which was 1.31-fold (95%CI 0.62-2.72) in CYP2C9 inhibiting SSRIs compared to non-users (table 2).
Conclusion(s): SSRIs are associated with an increased risk of high INR (≥ 5) and major bleeding. These risks were slightly more elevated for CYP2C9 inhibiting SSRI users, suggesting that this was due to a pharmacokinetic interaction (by CYP2C9 inhibition) as well as the effect of SSRIs on platelet activation. Therefore, we would suggest to prefer non-CYP2C9 inhibiting SSRIs for patients already using a VKA, and intensify monitoring of INR shortly after initiation of SSRI.
To cite this abstract in AMA style:
Burggraaf L, Bakker S, Kruip M, van der Meer F, Lijfering W, van Rein N. Selective serotonin reuptake inhibitor use is associated with major bleeding during treatment with vitamin K antagonists: results of a cohort study [abstract]. https://abstracts.isth.org/abstract/selective-serotonin-reuptake-inhibitor-use-is-associated-with-major-bleeding-during-treatment-with-vitamin-k-antagonists-results-of-a-cohort-study/. Accessed October 1, 2023.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/selective-serotonin-reuptake-inhibitor-use-is-associated-with-major-bleeding-during-treatment-with-vitamin-k-antagonists-results-of-a-cohort-study/