Evaluating Major Bleeding Risks with Concomitant Use of Direct Oral Anticoagulants and Selective Serotonin Reuptake Inhibitors in Nonvalvular Atrial Fibrillation Patients
Background/Objectives: Direct oral anticoagulants (DOACs), when compared to the Vitamin K antagonist (VKA) warfarin, exhibit greater safety and effectiveness. However, DOACs may still have potential drug–drug interactions that result in major bleeding events. There is a paucity of studies on medicat...
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MDPI AG
2025-03-01
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| Series: | Pharmacoepidemiology |
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| Online Access: | https://www.mdpi.com/2813-0618/4/1/6 |
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| author | Shu-Yu Yao Paul T. Kocis Terrence E. Murphy Wenke Hwang |
| author_facet | Shu-Yu Yao Paul T. Kocis Terrence E. Murphy Wenke Hwang |
| author_sort | Shu-Yu Yao |
| collection | DOAJ |
| description | Background/Objectives: Direct oral anticoagulants (DOACs), when compared to the Vitamin K antagonist (VKA) warfarin, exhibit greater safety and effectiveness. However, DOACs may still have potential drug–drug interactions that result in major bleeding events. There is a paucity of studies on medications that have pharmacodynamic interactions with DOACs, such as selective serotonin reuptake inhibitors (SSRIs). This study evaluates the potential major bleeding risk associated with the concomitant use of SSRIs among nonvalvular atrial fibrillation (NVAF) patients who were receiving DOACs. Methods: Adult patients receiving DOACs with consecutive NVAF diagnoses were identified from the Penn State Health Electronic Health Records from 2013 to 2023. These patients were then checked for exposure (i.e., concomitant use of SSRIs). The outcome was time to the first occurrence of a major bleeding event, with a follow-up from the first DOAC prescription until a major bleeding event, death, or end of follow-up. This retrospective cohort study used a Cox cause-specific proportional hazard model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with inverse probability of treatment weighting to adjust for measurable confounding factors (e.g., demographics, comorbidities, comedications). Results: A total of 8657 NVAF patients who were receiving DOACs were identified. The mean age was 70.3 ± 11.95 years, and females comprised 39.8% of the study population. The baseline CHA2DS2-VASc score was 3.77 ± 1.76, and the HAS-BLED score was 2.98 ± 1.27. Among these patients, 2649 (30.6%) were co-prescribed with SSRIs. The unadjusted hazard ratio for SSRIs was 0.87 (95% CI: 0.76–0.99) and the adjusted hazard ratio was 0.68 (95% CI: 0.59–0.78). Conclusions: In patients with NVAF receiving DOACs, concomitant use of SSRIs was not associated with a higher risk of major bleeding. |
| format | Article |
| id | doaj-art-99ce94f64b1b48beb59a920b4cb2884a |
| institution | Kabale University |
| issn | 2813-0618 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmacoepidemiology |
| spelling | doaj-art-99ce94f64b1b48beb59a920b4cb2884a2025-08-20T03:43:40ZengMDPI AGPharmacoepidemiology2813-06182025-03-0141610.3390/pharma4010006Evaluating Major Bleeding Risks with Concomitant Use of Direct Oral Anticoagulants and Selective Serotonin Reuptake Inhibitors in Nonvalvular Atrial Fibrillation PatientsShu-Yu Yao0Paul T. Kocis1Terrence E. Murphy2Wenke Hwang3Department of Public Health Sciences, Penn State College of Medicine, 90 Hope Drive, Hershey, PA 17033, USADepartment of Pharmacology, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USADepartment of Public Health Sciences, Penn State College of Medicine, 90 Hope Drive, Hershey, PA 17033, USADepartment of Public Health Sciences, Penn State College of Medicine, 90 Hope Drive, Hershey, PA 17033, USABackground/Objectives: Direct oral anticoagulants (DOACs), when compared to the Vitamin K antagonist (VKA) warfarin, exhibit greater safety and effectiveness. However, DOACs may still have potential drug–drug interactions that result in major bleeding events. There is a paucity of studies on medications that have pharmacodynamic interactions with DOACs, such as selective serotonin reuptake inhibitors (SSRIs). This study evaluates the potential major bleeding risk associated with the concomitant use of SSRIs among nonvalvular atrial fibrillation (NVAF) patients who were receiving DOACs. Methods: Adult patients receiving DOACs with consecutive NVAF diagnoses were identified from the Penn State Health Electronic Health Records from 2013 to 2023. These patients were then checked for exposure (i.e., concomitant use of SSRIs). The outcome was time to the first occurrence of a major bleeding event, with a follow-up from the first DOAC prescription until a major bleeding event, death, or end of follow-up. This retrospective cohort study used a Cox cause-specific proportional hazard model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with inverse probability of treatment weighting to adjust for measurable confounding factors (e.g., demographics, comorbidities, comedications). Results: A total of 8657 NVAF patients who were receiving DOACs were identified. The mean age was 70.3 ± 11.95 years, and females comprised 39.8% of the study population. The baseline CHA2DS2-VASc score was 3.77 ± 1.76, and the HAS-BLED score was 2.98 ± 1.27. Among these patients, 2649 (30.6%) were co-prescribed with SSRIs. The unadjusted hazard ratio for SSRIs was 0.87 (95% CI: 0.76–0.99) and the adjusted hazard ratio was 0.68 (95% CI: 0.59–0.78). Conclusions: In patients with NVAF receiving DOACs, concomitant use of SSRIs was not associated with a higher risk of major bleeding.https://www.mdpi.com/2813-0618/4/1/6DOACsSSRIsNVAFdrug–drug interactionsmajor bleeding risk |
| spellingShingle | Shu-Yu Yao Paul T. Kocis Terrence E. Murphy Wenke Hwang Evaluating Major Bleeding Risks with Concomitant Use of Direct Oral Anticoagulants and Selective Serotonin Reuptake Inhibitors in Nonvalvular Atrial Fibrillation Patients Pharmacoepidemiology DOACs SSRIs NVAF drug–drug interactions major bleeding risk |
| title | Evaluating Major Bleeding Risks with Concomitant Use of Direct Oral Anticoagulants and Selective Serotonin Reuptake Inhibitors in Nonvalvular Atrial Fibrillation Patients |
| title_full | Evaluating Major Bleeding Risks with Concomitant Use of Direct Oral Anticoagulants and Selective Serotonin Reuptake Inhibitors in Nonvalvular Atrial Fibrillation Patients |
| title_fullStr | Evaluating Major Bleeding Risks with Concomitant Use of Direct Oral Anticoagulants and Selective Serotonin Reuptake Inhibitors in Nonvalvular Atrial Fibrillation Patients |
| title_full_unstemmed | Evaluating Major Bleeding Risks with Concomitant Use of Direct Oral Anticoagulants and Selective Serotonin Reuptake Inhibitors in Nonvalvular Atrial Fibrillation Patients |
| title_short | Evaluating Major Bleeding Risks with Concomitant Use of Direct Oral Anticoagulants and Selective Serotonin Reuptake Inhibitors in Nonvalvular Atrial Fibrillation Patients |
| title_sort | evaluating major bleeding risks with concomitant use of direct oral anticoagulants and selective serotonin reuptake inhibitors in nonvalvular atrial fibrillation patients |
| topic | DOACs SSRIs NVAF drug–drug interactions major bleeding risk |
| url | https://www.mdpi.com/2813-0618/4/1/6 |
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