Selective Serotonin Reuptake Inhibitor Use and Risk of Major Bleeding during Treatment with Vitamin K Antagonists: Results of A Cohort Study.
| Autor: | Bakker S; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands., Burggraaf JLI; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands., Kruip MJHA; Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.; Star-shl Thrombosis Service, Rotterdam, The Netherlands., van der Meer FJM; Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands., Lijfering WM; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands., van Rein N; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. |
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| Jazyk: | angličtina |
| Zdroj: | Thrombosis and haemostasis [Thromb Haemost] 2023 Feb; Vol. 123 (2), pp. 245-254. Date of Electronic Publication: 2022 Oct 08. |
| DOI: | 10.1055/a-1957-6305 |
| Abstrakt: | Background: Selective serotonin reuptake inhibitors (SSRIs) may increase the risk of major bleeding by decreasing platelet function or decreasing vitamin K antagonist (VKA) metabolism via cytochrome P450 (CYP) inhibition. Aims: To determine whether SSRIs are associated with major bleeding during VKA treatment and investigate the possible mechanisms. Methods: In this cohort study, information on SSRI use and bleeding complications was obtained from patient records of VKA initiators between 2006 and 2018 from two anticoagulation clinics. Conditional logistic regression and time-dependent Cox regression were used to estimate the effect of SSRIs on a high international normalized ratio (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. Results: A total of 58,918 patients were included, of whom 1,504 were SSRI users. SSRI initiation versus nonuse 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 SSRI users. The adjusted hazard ratio of major bleeding was 1.22 (95% CI: 0.99-1.50) in all SSRI users and 1.31 (95% CI: 0.62-2.72) in CYP2C9-inhibiting SSRI users compared with nonusers. Conclusion: SSRI use is associated with an increased risk of high INR and might be associated with major bleeding. The risk of a high INR was slightly more elevated for CYP2C9-inhibiting SSRI users, suggesting there might be a pharmacokinetic interaction (by CYP2C9 inhibition) next to a pharmacodynamic effect of SSRIs on platelet activation. Competing Interests: None declared. (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).) |
| Databáze: | MEDLINE |
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