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

Prior stroke was the strongest independent factor associated with acute ischemic stroke in NOAC-treated atrial fibrillation patients.

• Adjusted odds ratio for prior stroke was 32.79, the highest of all factors examined
• This association was identified through multivariable logistic regression analysis
• The study included 112 AIS cases and 210 outpatient controls without AIS
• Patients with AIS more often had a history of prior stroke compared to controls in unadjusted comparisons as well

Prescribed reduced-dose NOAC use was independently associated with acute ischemic stroke in adjusted analysis.

• Adjusted odds ratio for prescribed reduced-dose NOAC use was 2.55
• Patients with AIS were more often prescribed reduced-dose NOACs than controls in unadjusted group comparisons
• All patients had received NOAC therapy for at least 3 months prior to the study assessment
• The study did not assess adherence, only prescribed dose

Coronary artery disease was independently associated with acute ischemic stroke with an odds ratio of 3.47.

• Adjusted OR = 3.47 for coronary artery disease
• Patients with AIS more often had coronary artery disease than controls in unadjusted comparisons
• Other cardiovascular comorbidities including hypertension, diabetes mellitus, and chronic kidney disease were also more prevalent in AIS patients
• Coronary artery disease ranked as the second strongest independent factor after prior stroke

Female sex, diabetes mellitus, and C-reactive protein were each independently associated with acute ischemic stroke.

• Adjusted OR for female sex was 2.26
• Adjusted OR for diabetes mellitus was 1.99
• Adjusted OR for C-reactive protein was 1.10 per mg/L increase
• CRP was measured during the acute stroke hospitalization, which the authors note limits interpretation of its role as a predisposing factor

Both HAS-BLED and CHA2DS2-VASc scores distinguished AIS cases from controls with high discriminative ability in exploratory ROC analyses.

• HAS-BLED AUC = 0.881 (95% CI: 0.844–0.918)
• CHA2DS2-VASc AUC = 0.840 (95% CI: 0.795–0.885)
• These analyses were described as exploratory
• The authors noted these findings do not estimate stroke incidence or future stroke risk due to the case-control design

AIS patients were older and had higher prevalence of multiple comorbidities compared to NOAC-treated AF controls without AIS.

• AIS patients were older than controls at the time of study assessment
• AIS group had higher rates of hypertension, diabetes mellitus, coronary artery disease, chronic kidney disease, and prior stroke
• The study was a retrospective 2-center case-control design with 322 total patients (112 AIS cases, 210 controls)
• All participants had non-valvular AF and had received NOAC therapy for at least 3 months

Inflammatory markers measured during the acute stroke period provided limited additional discriminative value beyond established clinical factors.

• C-reactive protein was statistically associated with AIS in adjusted analysis (OR = 1.10 per mg/L), but authors concluded inflammatory markers had 'limited additional value'
• CRP was measured during acute hospitalization, making it difficult to distinguish pre-existing inflammation from acute stroke-related inflammation
• The authors highlighted this as a limitation in interpreting the role of inflammatory markers
• Prospective validation was recommended before applying these findings clinically