Acute ischemic stroke or TIA despite DOAC treatment: the contribution of DOAC plasma levels to understand pathophysiological mechanisms

Background: Ischemic stroke or transient ischemic attack (TIA) occurs in 1.4% of patients with atrial fibrillation (AF) per year despite treatment with direct oral anticoagulants (DOACs). This group of patients is poorly studied, and possible causes for this are not fully understood. Objectives: The aim of the study was to analyze DOAC plasma levels in patients who had ischemic stroke or TIA despite treatment with DOAC. Design: Monocentric retrospective study. Methods: We selected consecutive DOAC-treated patients with acute ischemic stroke or TIA, admitted during a 2-year period, with measurement of DOAC levels ⩽24 h after hospital admission. Patients with and without low DOAC levels (48 h before admission (72.5% vs 57.5%, p = 0.004), and had higher baseline NIHSS (8 vs 4, p = 0.001). Lower DOAC levels were associated with large or medium vessel occlusion (LVO/MeVO; odds ratio per 10 ng/mL-increase = 0.89, 95% confidence interval = 0.85–0.94, p < 0.001). Cardiac pathology as the only potentially causal mechanism was more frequent in low DOAC levels patients (76.8% vs 60.6%, p = 0.029). Thirty patients (18.4%) had ⩾2 potentially causal mechanisms, 18 (11.0%) had potentially causal mechanisms other than cardiac pathology, and 5 (3.1%) had no identifiable potentially causal mechanism. Conclusion: In DOAC-treated patients with ischemic stroke or TIA, low DOAC levels were found in 2/5 of patients. Lower DOAC levels are associated with increased stroke severity and the presence of LVO/MeVO. The profile of stroke etiology in DOAC-treated patients varies between groups with and without low DOAC levels.