Drug-drug interactions with direct oral anticoagulants for the prevention of ischemic stroke and embolism in atrial fibrillation: a narrative review of adverse events

Link to article at PubMed

Expert Rev Clin Pharmacol. 2023 Mar 2. doi: 10.1080/17512433.2023.2187376. Online ahead of print.


INTRODUCTION: In randomized trials, direct oral anticoagulants (DOAC) were non-inferior to the vitamin-K-antagonist (VKA) warfarin in preventing stroke/embolism in patients with atrial fibrillation (AF). DOAC are substrates for P-glycoprotein (P-gp), CYP3A4 and CYP2C9. The activity of these enzymes is modulated by several drugs which might induce pharmacokinetic drug-drug interactions (DDI). Drugs affecting platelet function have the potential for pharmacodynamic DDI of DOAC.

AREAS COVERED: The literature was searched for: "dabigatran", "rivaroxaban", "edoxaban", or "apixaban" and drugs affecting platelet function, CYP3A4-, CYP2C9- or P-gp-activity. Reports about bleeding and embolic events attributed to DDI with DOAC in AF-patients were found for 43 of 171 drugs with interacting potential (25%), most frequently with antiplatelet and nonsteroidal anti-inflammatory drugs. Whereas a co-medication of platelet-affecting drugs is invariably reported to increase the bleeding risk, the findings regarding P-gp-, CYP3A4- and CYP2C9- activity-affecting drugs are ambiguous.

EXPERT OPINION: Tests for plasma DOAC-levels and information about DDI of DOAC should be widely available and user-friendly. If advantages and disadvantages of DOAC and VKA can be investigated exhaustively, individualized anticoagulant therapy can be offered to patients, considering co-medication, comorbidities, genetic and geographic factors and the health care system.

PMID:36861431 | DOI:10.1080/17512433.2023.2187376

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