These interactions are even more important considering that the VKAs have narrow therapeutic window. Genetic polymorphisms, particularly in the CYP2C9 and VKORC1 genes, can also significantly affect the response of AF patients to warfarin therapy.
The manufacturer itself provides a list of over 200 drugs that can interfere with the anticoagulant effect of warfarin, and the list of food interactions is almost as generous. However, its complex pharmacokinetics makes warfarin the target of numerous interactions. Due to its wide availability, low cost, and easy-to-administer antidote, warfarin is widely used for stroke prevention in AF patients and is the preferred oral anticoagulant in patients with mitral stenosis, valve replacement, or advanced renal disease. With its ability to reduce the risk of stroke by more than two-thirds and mortality by one-quarter compared with control (aspirin or no therapy), warfarin is one of the most efficient prophylactic strategies that medicine has ever known. In this paper, we aim to provide a comprehensive review of the bleeding risk associated with oral anticoagulant therapy in AF patients, with a highlight on the latest insights into GIB associated with oral anticoagulation we emphasize questions that remain to be answered and we identify hotspots for future research. Until then, the assessment of bleeding risk factors remains the only available tool, although the extent to which each of these factors contributes to the risk of bleeding is unknown. Accurate bleeding (including GIB-specific) risk scores specific for DOACs remain to be developed. Although the overall bleeding risk appears to be lower, the use of DOACs has been associated with an increased risk of GIB compared to warfarin. Using dose-adjusted warfarin increases threefold the risk of gastrointestinal bleeding (GIB). However, assessing the bleeding risk in patients receiving oral anticoagulants remains-particularly in the case of DOACs-highly challenging. Current guidelines recommend direct oral anticoagulants (DOACs) over warfarin for stroke prevention in most AF patients, mainly due to the ease of their use. Stroke prevention is accompanied by non-negligible risks, making anticoagulant treatment an ongoing challenge for the clinician. The rising prevalence and the complexity of atrial fibrillation (AF) pose major clinical challenges.
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