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6.2 Oral anticoagulants Vitamin K antagonists (VKA), predominantly warfarin but also other coumarin and indandione derivatives, have been the principal drugs to prevent thromboembolic events in the context of AF. As with any anticoagulant, a balance must be reached between preventing thromboembolism and preserving physiological haemostasis, with VKA-associated intracranial and other major haemorrhage the most critical limitation for acceptance of OAC. The global switch to DOACs as first-line therapy has changed this risk–benefit balance, allowing more widespread prescription with no need for routine monitoring (see Supplementary data online, Additional Evidence Tables S5–S7). This component of AF management may see substantive changes in the coming years, with a number of factor XI inhibitors in various stages of clinical evaluation. A phase 2 trial of abelacimab in patients with AF has shown lower rates of bleeding compared with rivaroxaban286; however, a phase 3 trial of asundexian was terminated early due to lack of efficacy against apixaban (NCT05643573), despite favourable phase 2 results.287 Regardless of the type of OAC prescribed, healthcare teams should be aware of the potential for interactions with other drugs, foods, and supplements, and incorporate this information into the education provided to patients and their carers. The list of potential interactions with VKA is broad,288,289 but there are also some common cardiovascular and non-cardiovascular drugs that interact with DOACs.290,291 Figure 9 highlights common and major interactions to consider for VKAs and DOACs. Caution if renal function impaired Vitamin K antagonist oral anticoagulants Avoid where possible NSAIDs Fluconazole Voriconazole Fluoxetine Avoid where possible Carbamazepine Phenytoin Phenobarbital Rifampicin Ritonavir Itraconazole Ketoconazole Avoid where possible Dronedarone Carbamazepine Phenytoin Rifampicin Ritonavir Itraconazole Ketoconazole Cyclosporin Glecaprevir/pibrentasvir Tacrolimus Avoid where possible Carbamazepine Phenytoin Phenobarbital Rifampicin Ritonavir Avoid where possible Dronedarone Carbamazepine Phenytoin Phenobarbital Itraconazole Ketoconazole Posaconazole Voriconazole Rifampicin Ritonavir Limit consumption Avoid or reduce apixaban dose if another interacting drug therapy Avoid if another interacting drug therapy Avoid or reduce edoxaban dose if another interacting drug therapy Avoid or reduce edoxaban dose Reduce warfarin dose Apixaban Dabigatran Edoxaban Delay timing of drugs and/or adjust dose Amiodarone Metronidazole Sulphonamides Allopurinol Fluvastatin Gemfibrozil Fluorouracil Increase warfarin dose Carbamazepine Monitor INR carefully Dronedarone Statins Penicillin antibiotics Macrolide antibiotics Quinolone antibiotics Rifampicin Methotrexate Ritonavir Phenytoin Sodium valproate Tamoxifen Chemotherapies Posaconazole Voriconazole Protease inhibitors Apalutamide Enzalutamide Tyrosine kinase inhibitors Limit consumption Grapefruit juice St John’s wort Limit consumption Grapefruit juice St John’s wort Limit consumption Grapefruit juice St John’s wort Limit consumption Grapefruit juice St John’s wort Amiodarone Ticagrelor Verapamil Quinidine Clarithromycin Posaconazole Dronedarone Protease inhibitors Tyrosine kinase inhibitors Verapamil Cyclosporin Clarithromycin Erythromycin Fluconazole Cyclosporin Itraconazole Ketoconazole Erythromycin Alcohol Grapefruit/cranberry juice St John’s wort Rivaroxaban Direct oral anticoagulants Figure 9 Common drug interactions with oral anticoagulants. INR, international normalized ratio of prothrombin time; NSAID, non-steroidal antiinflammatory drug. This figure depicts only common or major interactions and is not an exhaustive list of all potential interactions. Please see the European Medicines Agency website or your local formulary for more information. ESC Guidelines 3343 Downloaded from academic.oup.com/eurheartj/article/45/36/3314/7738779 by guest on 07 October 2026