Comprehensive Exploration of Medications That Affect the Bleeding Risk of Oral Anticoagulant Users
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- Kawano Yohei
- Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
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- Nagata Masashi
- Department of Pharmacy, Medical Hospital, Tokyo Medical and Dental University (TMDU)
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- Nakamura Saeko
- Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
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- Akagi Yuuki
- Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS) Department of Pharmacy, National Hospital Organization Yokohama Medical Center
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- Suzuki Tatsunori
- Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
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- Tsukada Emi
- Center Hospital of the National Center for Global Health and Medicine (NCGM)
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- Hoshiko Mai
- Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
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- Kujirai Azusa
- Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
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- Nakamatsu Satoshi
- Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
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- Nishikawa Tomoki
- Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
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- Enomoto Aya
- Department of Pharmacy, Medical Hospital, Tokyo Medical and Dental University (TMDU)
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- Negishi Kenichi
- Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
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- Shimada Shuji
- Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
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- Aoyama Takao
- Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
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- Mano Yasunari
- Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
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Description
<p>Oral anticoagulants (OACs) pose a major bleeding risk, which may be increased or decreased by concomitant medications. To explore medications that affect the bleeding risk of OACs, we conducted a nested case-control study including 554 bleeding cases (warfarin, n = 327; direct OACs [DOACs], n = 227) and 1337 non-bleeding controls (warfarin, n = 814; DOACs, n = 523), using a Japanese health insurance database from January 2005 to June 2017. Major bleeding risk associated with exposure to concomitant medications within 30 d of the event/index date was evaluated, and adjusted odds ratios (aORs) were calculated using logistic regression analysis. Several antihypertensive drugs, such as amlodipine and bisoprolol, were associated with a decreased risk of bleeding (warfarin + amlodipine [aOR, 0.64; 95% confidence interval (CI): 0.41–0.98], DOACs + bisoprolol [aOR, 0.51; 95% CI, 0.33–0.80]). As hypertension is considered a significant risk factor for intracranial bleeding in antithrombotic therapy, antihypertensive drugs may suppress intracranial bleeding. In contrast, telmisartan, a widely used antihypertensive drug, was associated with an increased risk of bleeding [DOACs + telmisartan (aOR, 4.87; 95% CI, 1.84–12.91)]. Since telmisartan is an inhibitor of P-glycoprotein (P-gp), the elimination of rivaroxaban and apixaban, which are substrates of P-gp, is hindered, resulting in increased blood levels of both drugs, thereby increasing the risk of hemorrhage. In conclusion, antihypertensive drugs may improve the safety of OACs, and the pharmacokinetic-based drug interactions of DOACs must be considered.</p>
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 44 (5), 611-619, 2021-05-01
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390569382247928960
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- NII Article ID
- 130008033161
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- NII Book ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 031424799
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- PubMed
- 33952817
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed