Acute ischemic stroke despite NOAC therapy in atrial fibrillation: Clinical factors associated with AIS in a 2-center observational case-control study.

Acute ischemic stroke (AIS) can occur in patients with non-valvular atrial fibrillation (AF) despite treatment with non-vitamin K antagonist oral anticoagulants (NOACs). This study evaluated clinical, treatment-related, inflammatory, and echocardiographic factors associated with AIS in NOAC-treated patients with AF. This retrospective, 2-center case-control study included 322 patients with non-valvular AF who had received NOAC therapy for at least 3 months. Of these, 112 were hospitalized with AIS and 210 were outpatient controls without AIS at the study assessment. Group differences and factors associated with AIS were evaluated using multivariable logistic regression. ROC analyses were exploratory. Patients with AIS were older than controls and more often had hypertension, diabetes mellitus, coronary artery disease, chronic kidney disease, prior stroke, and prescribed reduced-dose NOAC use. In the adjusted analysis, prior stroke (OR = 32.79), coronary artery disease (OR = 3.47), prescribed reduced-dose NOAC use (OR = 2.55), female sex (OR = 2.26), diabetes mellitus (OR = 1.99), and C-reactive protein (OR per mg/L = 1.10) were associated with AIS. HAS-BLED (area under the curve = 0.881, 95% CI = 0.844-0.918) and CHA2DS2-VASc (area under the curve = 0.840, 95% CI = 0.795-0.885) distinguished AIS cases from controls in exploratory ROC analyses. Among NOAC-treated patients with AF, prior stroke and cardiovascular comorbidities were strongly associated with AIS. Prescribed reduced-dose NOAC use was also associated with AIS. Inflammatory markers measured during acute stroke had limited additional value. Because this was a case-control study, the findings do not estimate stroke incidence or future stroke risk and require prospective validation.