• Ann Acad Med Singap · Feb 2024

    Effect of drug interactions with non-vitamin-K oral anticoagulants on thromboembolic events in patients with nonvalvular atrial fibrillation.

    • Jin-Hua Chen, Ming-Chia Lee, Tzu-Hsin Yen, Pei-Yu Huang, De-En Lu, Chih-Hsin Lee, Hsien-Chen Chang, Jann-Yuan Wang, and Jen-Ai Lee.
    • Biostatistics Center, College of Management, Taipei Medical University, Taipei, Taiwan.
    • Ann Acad Med Singap. 2024 Feb 28; 53 (2): 697969-79.

    IntroductionFew real-world studies have investigated drug-drug interactions (DDIs) involving non-vitamin-K antagonist oral anticoagulants (NOACs) in patients with nonvalvular atrial fibrillation (NVAF). The interactions encompass drugs inducing or inhibiting cytochrome P450 3A4 and permeability glycoprotein. These agents potentially modulate the breakdown and elimination of NOACs. This study investigated the impact of DDIs on thromboembolism in this clinical scenario.MethodPatients who had NVAF and were treated with NOACs were selected as the study cohort from the National Health Insurance Research Database of Taiwan. Cases were defined as patients hospitalised for a thromboembolic event and who underwent a relevant imaging study within 7 days before hospitalisa-tion or during hospitalisation. Each case was matched with up to 4 controls by using the incidence density sampling method. The concurrent use of a cytochrome P450 3A4/permeability glycoprotein inducer or inhibitor or both with NOACs was identified. The effects of these interactions on the risk of thromboembolic events were examined with univariate and multivariate conditional logistic regressions.ResultsThe study cohort comprised 60,726 eligible patients. Among them, 1288 patients with a thromboembolic event and 5144 matched control patients were selected for analysis. The concurrent use of a cytochrome P450 3A4/permeability glycoprotein inducer resulted in a higher risk of thromboembolic events (adjusted odds ratio [AOR] 1.23, 95% confidence interval [CI] 1.004-1.51).ConclusionFor patients with NVAF receiving NOACs, the concurrent use of cytochrome P450 3A4/ permeability glycoprotein inducers increases the risk of thromboembolic events.

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