- 著者
-
Yohei Kawano
Masashi Nagata
Saeko Nakamura
Yuuki Akagi
Tatsunori Suzuki
Emi Tsukada
Mai Hoshiko
Azusa Kujirai
Satoshi Nakamatsu
Tomoki Nishikawa
Aya Enomoto
Kenichi Negishi
Shuji Shimada
Takao Aoyama
Yasunari Mano
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Biological and Pharmaceutical Bulletin (ISSN:09186158)
- 巻号頁・発行日
- vol.44, no.5, pp.611-619, 2021-05-01 (Released:2021-05-01)
- 参考文献数
- 41
- 被引用文献数
-
2
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.