Title:Effectiveness and Safety of Different Oral Anticoagulants with P-glycoprotein/
CYP3A4 Inhibitors: A Network Meta-analysis
Volume: 30
Issue: 15
Author(s): Siyu Yang, Ye Xu, Yang Zhang, Dandan Li*Xingang Li*
Affiliation:
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China
Keywords:
Oral anticoagulant, P-gp/CYP3A4 inhibitor, effectiveness and safety, bleeding risk, network meta-analysis, intracranial hemorrhage.
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.
