Effectiveness and Safety of Different Oral Anticoagulants with P-glycoprotein/ CYP3A4 Inhibitors: A Network Meta-analysis
- Authors: Yang S.1, Xu Y.2, Zhang Y.2, Li D.2, Li X.1
-
Affiliations:
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University,
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University
- Issue: Vol 30, No 15 (2024)
- Pages: 1167-1177
- Section: Immunology, Inflammation & Allergy
- URL: https://vestnikugrasu.org/1381-6128/article/view/645618
- DOI: https://doi.org/10.2174/0113816128293940240315073345
- ID: 645618
Cite item
Full Text
Abstract
Background:Metabolism of oral anticoagulants (OAC) is affected by P-glycoprotein (P-gp)/ CYP3A4 enzyme. However, the P-gp/CYP3A4 inhibitors are unavoidably used with OACs.
Methods:Medline, Cochrane, and Embase were systematically searched for randomized controlled trials and cohort studies from inception till 23rd November, 2022 to assess the safety and effectiveness of OACs when concomitantly used with P-gp/CYP3A4 inhibitors. The primary outcomes were major bleeding and gastrointestinal (GI) bleeding. Secondary outcomes were stroke/systemic embolism (SE), all-cause mortality, any bleeding as well as intracranial hemorrhage (ICH). We estimated summary odds ratios (OR) with 95% credible intervals (CI) using pairwise and network meta-analysis with random effects
Results:A total of 11 studies involving 37,973 patients were included. When concomitantly used with P-pg/ CYP3A4 inhibitors, network meta-analysis indicated that dabigatran, apixaban, and edoxaban were associated with significantly lower risk of major bleeding compared to rivaroxaban, with ORs of 0.56, 0.51 and 0.48, respectively. Rivaroxaban and dabigatran were associated with a significantly increased risk of GI bleeding than warfarin, apixaban and edoxaban. Dabigatran and apixaban were linked with significantly lower risk of any bleeding compared with warfarin (ORs were 0.75 and 0.68, respectively) or rivaroxaban (ORs were 0.67 and 0.60, respectively). Apixaban (OR 0.32) and edoxaban (OR 0.35) were associated with a lower risk of ICH compared with warfarin. There was no difference between any OACs in terms of stroke/SE or all-cause mortality.
Conclusion:When concomitantly used with P-gp/CYP3A4 inhibitors, apixaban and edoxaban were associated with a lower risk of bleeding, though no significant difference in effectiveness was observed among all OACs.
About the authors
Siyu Yang
Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University,
Email: info@benthamscience.net
Ye Xu
Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University
Email: info@benthamscience.net
Yang Zhang
Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University
Email: info@benthamscience.net
Dandan Li
Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University
Author for correspondence.
Email: info@benthamscience.net
Xingang Li
Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University,
Author for correspondence.
Email: info@benthamscience.net
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