Non-vitamin K Antagonist Oral Anticoagulants (NOACs) Versus Warfarin in Patients with Atrial Fibrillation Using P-gp and/or CYP450-Interacting Drugs: a Systematic Review and Meta-analysis

Maxim Grymonprez*, Kevin Vanspranghe, Stephane Steurbaut, Tine L. De Backer, Lies Lahousse

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

Purpose: Non-vitamin K antagonist oral anticoagulants (NOACs) are excreted by P-glycoprotein (P-gp) and some are metabolized by CYP450 enzymes such as CYP3A4. Although fewer drug interactions are present with NOACs, it is unclear whether NOACs should also be preferred over vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) using pharmacokinetically interacting drugs. Therefore, the benefit-risk profile of NOACs versus VKAs was investigated in AF patients treated with P-gp and/or CYP450-interacting drugs. Methods: Using PubMed and Embase, randomized controlled trials and observational studies on the effectiveness and safety of NOACs versus VKAs in AF patients using P-gp and/or CYP450-interacting drugs were included. A meta-analysis was performed, calculating relative risks (RR) and 95% confidence intervals (CI) with the Mantel–Haenszel method. Results: Twelve studies were included, investigating 10,793 NOAC and 10,096 VKA users treated with P-gp/CYP3A4 inhibitors, whereas no studies on P-gp and/or CYP450-inducing drugs were identified. Compared to VKAs, NOACs were associated with a borderline non-significantly lower stroke or systemic embolism (stroke/SE) risk (RR 0.85, 95%CI (0.72–1.01)), significantly lower intracranial bleeding (RR 0.47, 95%CI (0.34–0.65)) and all-cause mortality risks (RR 0.87, 95%CI (0.79–0.95), but significantly higher gastrointestinal bleeding risk (RR 1.74, 95%CI (1.06–2.86)). Among AF patients using amiodarone, NOACs were associated with significantly lower stroke/SE (RR 0.71, 95%CI (0.54–0.93)) and intracranial bleeding risks (RR 0.51, 95%CI (0.29–0.88)), but significantly higher gastrointestinal bleeding risk (RR 2.15, 95%CI (1.24–3.72)) than VKAs. Conclusion: The benefit-risk profile of NOACs compared to VKAs was preserved in AF patients using P-gp/CYP3A4 inhibitors, including amiodarone.

Original languageEnglish
JournalCardiovascular Drugs and Therapy
DOIs
Publication statusE-pub ahead of print - 12 Oct 2021

Bibliographical note

Funding Information:
This work was supported by grants from the Research Foundation Flanders (FWO) [Grant number 11C0820N to Maxim Grymonprez].

Publisher Copyright: © 2021, Springer Science+Business Media, LLC, part of Springer Nature.

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