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.

Keywords: Anticoagulants; Atrial fibrillation; Ischemic stroke; Left atrial appendage; Non-vitamin K antagnoist oral anticoagulants.

Figure 1.

Competing mechanism: high-resonance magnetic resonance imaging (MRI) findings of a 69-year-old man with atrial fibrillation on anticoagulated with edoxaban. (A) He experienced transient right hemiparesis. He was taking edoxaban with good adherence. Magnetic resonance (MR) angiogram shows focal stenosis on the distal M1 segment. No acute infarct is observed on diffusion-weighted imaging and MR perfusion showed perfusion delay on the left middle cerebral artery hemisphere. High resonance MRI shows intraplaque hemorrhage on T1-weighted images (arrow) and eccentric wall thickening and enhancement on contrast-enhanced T1-weighted images (arrowhead) suggesting unstable intracranial plaque. The echocardiogram showed no cardiac thrombi and left atrial enlargement was not prominent. Clopidogrel and a high-dose statin were added to edoxaban. (B) A follow-up high-resolution MRI at 6 months of treatment. Plaque enhancement disappears (arrowhead). TOF-MRA, time-of-flight magnetic resonance angiography.

Figure 2.

Recurrent cardioembolism despite sufficient anticoagulation: a 76-year-old woman experienced recurrent stroke despite sufficient anticoagulation. (A) Warfarin was switched to rivaroxaban owing to poor international normalized ratio control. She was a CYP2C9 *1/1* and VKORC1 TT carrier suggesting extensive metabolizer and high warfarin sensitivity. Dabigatran was started after recurrent stroke despite good adherence to rivaroxaban. Finally, surgical LAA exclusion and Maze operation were performed. (B) Serial multidetector cardiac computed tomography shows an enlargement of LA and LAA volume and the development of a 2 cm-sized LAA thrombus. Echocardiography also showed increased LA volume index from 44 mL/m² to 57 mL/m². LAA, left atrial appendage; LA, left atrium.

Figure 3.

Percutaneous left atrial appendage (LAA) occluder devices: (A) PLAATO, (B) WATCHMAN, and (C) Amplatzer. Echocardiographic views of the devices: (D) WATCHMAN and (E) Amplatzer. LA, left atrium; white arrow, LAA; white triangle, LAA occluder device.

Figure 4.

Epicardial left atrial appendage (LAA) exclusion: resection and occlusion. (A) Epicardial resection using a stapler. LAA is resected using a stapling device. A suture line at the base of LAA demonstrates no residual stump. (B) Epicardial occlusion with clip devices. LAA is occluded using a white-color clip device at the base of LAA. LAA is left unresected.

Figure 5.

Relative reduction of ischemic stroke with surgical left atrial appendage occlusion, compared with the predicted rate. Relative ischemic stroke reduction compared with the predicted rate. (A) Overall patients. (B) Patients other than those with CHA₂DS₂-VASc score 0. Adapted from Kim et al. Front Cardiovasc Med 2022;9:853299, under the terms of the Creative Commons Attribution License (CC BY) [71].