biostudies-literatureUnknown19Rust M<h4>Background</h4>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.<h4>Objectives</h4>The aim of the study was to analyze DOAC plasma levels in patients who had ischemic stroke or TIA despite treatment with DOAC.<h4>Design</h4>Monocentric retrospective study.<h4>Methods</h4>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 (<50 ng/mL) were compared.<h4>Results</h4>We included 163 patients with median age of 80 years, 46.6% of female sex. AF was the most frequent indication for DOAC (83.4%). Low DOAC levels were found in 42.3% of patients. Patients with low DOAC levels more frequently were being treated with an inappropriate low DOAC dose (29.4% vs 16.0%, <i>p</i> = 0.004), more frequently had unknown last DOAC intake or intake >48 h before admission (72.5% vs 57.5%, <i>p</i> = 0.004), and had higher baseline NIHSS (8 vs 4, <i>p</i> = 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, <i>p</i> < 0.001). Cardiac pathology as the only potentially causal mechanism was more frequent in low DOAC levels patients (76.8% vs 60.6%, <i>p</i> = 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.<h4>Conclusion</h4>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.Therapeutic advances in neurological disorders17562864261415719https://www.ebi.ac.uk/biostudies/studies/S-EPMC12901951biostudies-literatureAcute ischemic stroke or TIA despite DOAC treatment: the contribution of DOAC plasma levels to understand pathophysiological mechanisms.PMC12901951Schulz JBReich AWiesmann MRust MImohl MPinho JGozalan MNikoubashman OfalseAcute ischemic stroke or TIA despite DOAC treatment: the contribution of DOAC plasma levels to understand pathophysiological mechanisms.<h4>Background</h4>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.<h4>Objectives</h4>The aim of the study was to analyze DOAC plasma levels in patients who had ischemic stroke or TIA despite treatment with DOAC.<h4>Design</h4>Monocentric retrospective study.<h4>Methods</h4>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 (<50 ng/mL) were compared.<h4>Results</h4>We included 163 patients with median age of 80 years, 46.6% of female sex. AF was the most frequent indication for DOAC (83.4%). Low DOAC levels were found in 42.3% of patients. Patients with low DOAC levels more frequently were being treated with an inappropriate low DOAC dose (29.4% vs 16.0%, <i>p</i> = 0.004), more frequently had unknown last DOAC intake or intake >48 h before admission (72.5% vs 57.5%, <i>p</i> = 0.004), and had higher baseline NIHSS (8 vs 4, <i>p</i> = 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, <i>p</i> < 0.001). Cardiac pathology as the only potentially causal mechanism was more frequent in low DOAC levels patients (76.8% vs 60.6%, <i>p</i> = 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.<h4>Conclusion</h4>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.2026-01-01T00:00:00Z20262026-07-07T03:15:21.305Z2026-07-07T03:09:53.321ZS-EPMC129019514169667510.1177/17562864261415719