Occurrence of Ischemic Stroke in Patients With Atrial Fibrillation Receiving Non-Vitamin K Oral Anticoagulants: Causes and Prevention Strategies

Abstract

Atrial fibrillation (AF) is a leading cause of cardioembolic stroke, which is often fatal or disabling. Prevention of stroke is crucial in AF management, and anticoagulation with non-vitamin K oral anticoagulants (NOACs) is the mainstay of AF management for stroke prevention. Because NOAC prescriptions have been surging worldwide, the development of acute ischemic stroke in patients with AF who receive NOAC treatment is an increasingly important issue in clinical practice. Moreover, these patients show a high risk of recurrence, with more than a 50% higher risk, than do patients with AF and no prior anticoagulation therapy. Careful evaluation is mandatory to determine possible causes of ischemic stroke during NOAC therapy. Differentiation of AF-unrelated stroke and demonstration of combined cardiac disease/systemic coagulopathy are important in these patients and may provide improved results in their treatment. In addition, ensuring appropriate dosing and good adherence to NOAC treatment is important. Cardioembolism, despite sufficient anticoagulation and no other causes, is the most common and challenging complication because switching to anticoagulants or adding antiplatelets to the treatment regimen does not reduce the risk of recurrent stroke, and there are no guidelines for this specific situation. This review article aimed to present the most updated data on the prevalence, causes, and secondary prevention strategies, specifically focusing on non-pharmacological approaches, together with relevant cases of AF in patients who developed ischemic stroke on NOAC therapy.

Acute Ischaemic Stroke in Patients Treated with Direct Oral Anticoagulants: Potential Causes, Clinical Characteristics, and Short-Term Outcomes

“…During the last decade, our knowledge on AIS in patients with preceding DOAC treatment has vastly expanded [ 19 ]. Although AIS can occur even despite sufficient anticoagulation, a number of causes for DOAC treatment failure have been identified and researched [ 4 , 5 ]. Our study shows that a potential cause of AIS occurring in DOAC-treated patients can be identified in most cases and in many of them prevented.…”

“…With growing numbers of patients receiving DOAC in primary and secondary stroke prevention, the number of cases of AIS occurring in DOAC-treated patients is also increasing [ 4 , 8 ], making it important to continuously analyse their incidence, potential causes, clinical course, and outcomes.…”

“…Although significantly reduced, the risk of acute ischaemic stroke (AIS) in NVAF patients undergoing DOAC treatment is still present and is estimated to be 0.7%-2.3% per year, with higher risk values in secondary prevention [ 3 ]. Studies show that 20-36% of AIS in AF patients occur despite treatment with oral anticoagulants [ 4 ]. The potential causes of AIS occurring in DOAC-treated patients include noncompliance to treatment, inappropriate drug dosage, interactions with other medications, aetiology of stroke other than cardioembolic, residual risk, and treatment failure [ 5 ].…”

“…The use of DOAC in secondary stroke prevention also seems to be more beneficial than VKA, because if a recurrent infarct occurs, it also tends to be smaller in size [ 12 ]. At the same time, the number of DOAC users increases and so does the absolute number of patients with AIS occurring during DOAC treatment [ 4 ]. Some retrospective studies even suggest that the real-life incidence of AIS in anticoagulated patients may be higher on DOAC than on VKA, thus contradicting the results of clinical trials [ 13 ].…”

A cross-sectional study of appropriateness evaluation of anticoagulation therapy for inpatients with nonvalvular atrial fibrillation

“…Moreover, Asian patients are considered at high risk of hemorrhage and off-label dosage, especially under-dose of NOACs, is regularly prescribed by domestic physicians to patients with AF ( Cheng et al, 2019 ). Poor compliance with guidelines and off-label use of NOACs could cause adverse outcomes ( Bang et al, 2023 ). It is important to highlight compliance with anticoagulation therapy in alignment with guidelines and medication labels in practical clinical settings.…”