Concomitant Drug Interactions With Non–Vitamin K Oral Anticoagulants Are Associated With Bleeding and Mortality Risk in Patients With Nonvalvular Atrial Fibrillation
Background Non–vitamin K oral anticoagulants prevent stroke and systemic embolism in patients with nonvalvular atrial fibrillation. However, potential drug interactions with concomitant medications may compromise their efficacy and escalate the risk of adverse effects. Methods and Results We conduct...
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Wiley
2025-05-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.038668 |
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| author | Chun‐Ka Wong Yuen‐Kwun Wong Yap‐Hang Chan Minqing Lin Jojo Siu‐Han Hai Kai‐Hang Yiu Gregory YH Lip Kui‐Kai Lau Hung‐Fat Tse |
| author_facet | Chun‐Ka Wong Yuen‐Kwun Wong Yap‐Hang Chan Minqing Lin Jojo Siu‐Han Hai Kai‐Hang Yiu Gregory YH Lip Kui‐Kai Lau Hung‐Fat Tse |
| author_sort | Chun‐Ka Wong |
| collection | DOAJ |
| description | Background Non–vitamin K oral anticoagulants prevent stroke and systemic embolism in patients with nonvalvular atrial fibrillation. However, potential drug interactions with concomitant medications may compromise their efficacy and escalate the risk of adverse effects. Methods and Results We conducted a territory‐wide retrospective cohort study in Hong Kong, focusing on nonvalvular atrial fibrillation prescribed non–vitamin K oral anticoagulants. The objective was to investigate the associated risk of gastrointestinal bleeding, intracranial hemorrhage, hospitalization for major bleeding, and all‐cause mortality in relation to various concomitant medications. Our analysis included 22 568 patients with nonvalvular atrial fibrillation (aged 75.7 ± 10.8 years; 51.2% men) taking non–vitamin K oral anticoagulants from January 1, 2017, to December 31, 2020, totaling 40 317 patient‐years. It was found that amiodarone (hazard ratio [HR], 1.53), digoxin (HR, 1.30), diltiazem (HR, 1.18), clarithromycin (HR, 4.98), and fluconazole (HR, 2.38) were associated with increased gastrointestinal bleeding, whereas amiodarone (HR, 2.20) and digoxin (HR, 1.61) were associated with increased intracranial hemorrhage. Furthermore, amiodarone (HR, 1.64), digoxin (HR, 1.35), clarithromycin (HR, 4.18), and fluconazole (HR, 2.40) were associated with increased hospitalization for major bleeding. Additionally, amiodarone (HR, 2.65), digoxin (HR, 1.85), diltiazem (HR, 1.44), verapamil (HR, 1.80), antidepressants (HR, 1.31), and fluconazole (HR, 3.27) were associated with increased all‐cause mortality. Conversely, dronedarone (HR, 0.56) and atorvastatin (HR, 0.86) were associated with a significant reduction in all‐cause mortality. Conclusions For patients with nonvalvular atrial fibrillation taking non–vitamin K oral anticoagulants, several concurrent medications were associated with increased risks of intracranial hemorrhage, major bleeding hospitalizations, and overall mortality. |
| format | Article |
| id | doaj-art-0a7b24d32d634d2a8bcaad22ba1454da |
| institution | OA Journals |
| issn | 2047-9980 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-0a7b24d32d634d2a8bcaad22ba1454da2025-08-20T02:26:30ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-05-0114910.1161/JAHA.124.038668Concomitant Drug Interactions With Non–Vitamin K Oral Anticoagulants Are Associated With Bleeding and Mortality Risk in Patients With Nonvalvular Atrial FibrillationChun‐Ka Wong0Yuen‐Kwun Wong1Yap‐Hang Chan2Minqing Lin3Jojo Siu‐Han Hai4Kai‐Hang Yiu5Gregory YH Lip6Kui‐Kai Lau7Hung‐Fat Tse8Department of Medicine, School of Clinical Medicine Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR ChinaDepartment of Medicine, School of Clinical Medicine Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR ChinaDepartment of Medicine, School of Clinical Medicine Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR ChinaDepartment of Medicine, School of Clinical Medicine Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR ChinaDepartment of Medicine, School of Clinical Medicine Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR ChinaDepartment of Medicine, School of Clinical Medicine Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR ChinaLiverpool Centre for Cardiovascular Science University of Liverpool and Liverpool Heart and Chest Hospital Liverpool UKDepartment of Medicine, School of Clinical Medicine Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR ChinaDepartment of Medicine, School of Clinical Medicine Li Ka Shing Faculty of Medicine, The University of Hong Kong Hong Kong SAR ChinaBackground Non–vitamin K oral anticoagulants prevent stroke and systemic embolism in patients with nonvalvular atrial fibrillation. However, potential drug interactions with concomitant medications may compromise their efficacy and escalate the risk of adverse effects. Methods and Results We conducted a territory‐wide retrospective cohort study in Hong Kong, focusing on nonvalvular atrial fibrillation prescribed non–vitamin K oral anticoagulants. The objective was to investigate the associated risk of gastrointestinal bleeding, intracranial hemorrhage, hospitalization for major bleeding, and all‐cause mortality in relation to various concomitant medications. Our analysis included 22 568 patients with nonvalvular atrial fibrillation (aged 75.7 ± 10.8 years; 51.2% men) taking non–vitamin K oral anticoagulants from January 1, 2017, to December 31, 2020, totaling 40 317 patient‐years. It was found that amiodarone (hazard ratio [HR], 1.53), digoxin (HR, 1.30), diltiazem (HR, 1.18), clarithromycin (HR, 4.98), and fluconazole (HR, 2.38) were associated with increased gastrointestinal bleeding, whereas amiodarone (HR, 2.20) and digoxin (HR, 1.61) were associated with increased intracranial hemorrhage. Furthermore, amiodarone (HR, 1.64), digoxin (HR, 1.35), clarithromycin (HR, 4.18), and fluconazole (HR, 2.40) were associated with increased hospitalization for major bleeding. Additionally, amiodarone (HR, 2.65), digoxin (HR, 1.85), diltiazem (HR, 1.44), verapamil (HR, 1.80), antidepressants (HR, 1.31), and fluconazole (HR, 3.27) were associated with increased all‐cause mortality. Conversely, dronedarone (HR, 0.56) and atorvastatin (HR, 0.86) were associated with a significant reduction in all‐cause mortality. Conclusions For patients with nonvalvular atrial fibrillation taking non–vitamin K oral anticoagulants, several concurrent medications were associated with increased risks of intracranial hemorrhage, major bleeding hospitalizations, and overall mortality.https://www.ahajournals.org/doi/10.1161/JAHA.124.038668bleedingdrug interactionmortalitynonvalvular atrial fibrillationnon–vitamin K oral anticoagulant |
| spellingShingle | Chun‐Ka Wong Yuen‐Kwun Wong Yap‐Hang Chan Minqing Lin Jojo Siu‐Han Hai Kai‐Hang Yiu Gregory YH Lip Kui‐Kai Lau Hung‐Fat Tse Concomitant Drug Interactions With Non–Vitamin K Oral Anticoagulants Are Associated With Bleeding and Mortality Risk in Patients With Nonvalvular Atrial Fibrillation Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease bleeding drug interaction mortality nonvalvular atrial fibrillation non–vitamin K oral anticoagulant |
| title | Concomitant Drug Interactions With Non–Vitamin K Oral Anticoagulants Are Associated With Bleeding and Mortality Risk in Patients With Nonvalvular Atrial Fibrillation |
| title_full | Concomitant Drug Interactions With Non–Vitamin K Oral Anticoagulants Are Associated With Bleeding and Mortality Risk in Patients With Nonvalvular Atrial Fibrillation |
| title_fullStr | Concomitant Drug Interactions With Non–Vitamin K Oral Anticoagulants Are Associated With Bleeding and Mortality Risk in Patients With Nonvalvular Atrial Fibrillation |
| title_full_unstemmed | Concomitant Drug Interactions With Non–Vitamin K Oral Anticoagulants Are Associated With Bleeding and Mortality Risk in Patients With Nonvalvular Atrial Fibrillation |
| title_short | Concomitant Drug Interactions With Non–Vitamin K Oral Anticoagulants Are Associated With Bleeding and Mortality Risk in Patients With Nonvalvular Atrial Fibrillation |
| title_sort | concomitant drug interactions with non vitamin k oral anticoagulants are associated with bleeding and mortality risk in patients with nonvalvular atrial fibrillation |
| topic | bleeding drug interaction mortality nonvalvular atrial fibrillation non–vitamin K oral anticoagulant |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.038668 |
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