Is Atrial Fibrillation Always a Culprit of Stroke in Patients with Atrial Fibrillation plus Stroke?

Abstract

Background: Some ischemic strokes in patients with atrial fibrillation (AF) are caused by noncardioembolic etiologies (AF-unrelated stroke), but not AF itself (AF-related stroke). However, most clinical trials on the risk of stroke in AF have not distinguished between these. We investigated the frequency and features of AF-unrelated versus AF-related strokes in patients with AF plus ischemic stroke. We hypothesized that certain clinical factors, including chronicity of AF, treatment at the time of stroke onset and echocardiographic findings, may help to discriminate between AF-related and AF-unrelated strokes. The mechanisms and antithrombotic medications at the time of stroke recurrence in the two groups were also examined. Methods: Consecutive patients with ischemic stroke within 7 days of symptom onset and with AF were included. Patients were classified according to the previously published criteria. Clinical factors including CHADS₂ and CHA₂DS₂-VASc scores and transthoracic echocardiographic (TTE) findings were evaluated. Results: Of 522 patients, 424 (81.2%) were grouped as AF-related stroke and the remaining 90 (17.2%) were classified as AF-unrelated stroke. Among the patients with AF-unrelated stroke, 51 (9.8%) were categorized as possible large artery atherosclerosis and 38 (7.3%) as possible small artery occlusion; 1 patient (0.2%) was assigned to miscellaneous cause. The AF-related and AF-unrelated strokes had similar CHADS₂ and CHA₂DS₂-VASc scores. However, compared to AF-unrelated stroke, AF-related stroke was independently associated with female sex (odds ratio, OR, 2.19; 95% confidence interval, CI, 1.18-4.05), sustained AF (OR, 2.09; 95% CI, 1.21-3.59), inadequate anticoagulation at stroke onset (OR, 3.21; 95% CI, 1.33-7.75) and left ventricular dysfunction on TTE (OR, 2.84; 95% CI, 1.40-5.74). We identified 26 patients who experienced 2 strokes during the study period. The initial stroke subtype was a strong predictor of the recurrent stroke mechanism (p < 0.001). Among 17 events of AF-related recurrent stroke in these subpopulation, only 2 strokes (11.8%) occurred in a setting of adequate anticoagulation, whereas 4 out of 9 patients (44.4%) who had AF-unrelated strokes at recurrence were sufficiently anticoagulated at the time of admission (p = 0.138). Conclusion: AF is not always a culprit of stroke in patients with AF plus ischemic stroke; approximately one sixth of these cases are unrelated to AF and have distinct characteristics compared to AF-related stroke. There are significant differences in terms of some clinical and TTE parameters between AF-related and AF-unrelated stroke. Future studies are warranted to optimize strategies for risk stratification, treatment and prevention of stroke in these patients.

Implications of CHA₂DS₂-VASc Score in Stroke Patients with Atrial Fibrillation: An Analysis of 938 Korean Patients

“…Most clinical trials investigating the risk of stroke in patients with AF did not distinguish these factors [27,28,29,30]. Some studies emphasized that stroke in patients with AF is not always AF-related stroke, and anticoagulants may have a limited effect in the prevention of AF-unrelated stroke [7,8,31]. For example, approximately 20-50% of patients with AF have carotid artery stenosis [32,33].…”

“…The patients were divided into AF-related and AF-unrelated stroke groups according to presumed stroke subtypes based on the criteria published by the Stroke Prevention in Atrial Fibrillation investigators with some modifications (Table 1) [7,8,9,10]. …”

Non-vitamin K oral antagonist failure and tailored treatment in patients with atrial fibrillation and stroke

“…The incidences of strokes that occur in one third of the patients are unrelated to Afib. The incidence of strokes in one in every seven patients had a non-Afib pathogenesis [17]. The infarct pattern revealed by the DWI was correlated with its underlying pathogenic mechanisms [18].…”

Asian Patients with Stroke plus Atrial Fibrillation and the Dose of Non-Vitamin K Oral Anticoagulants

“…Since macro- and microangiopathies are more prevalent in Asians than in non-Asians, AF-unrelated stroke/TIA is more likely to occur in Asian AF patients than in non-Asian AF patients. In a Korean study, among AF patients with recent ischemic stroke, 17.2% of ischemic strokes were classified as AF-unrelated strokes [ 38 ]. Moreover, compared to patients with AF-related stroke, patients with AF-unrelated stroke experienced more recurrent strokes even with adequate anticoagulation, and 87.5% of their recurrent strokes were AF-unrelated strokes [ 38 ].…”