Direct oral anticoagulant concentrations and adherence in stroke patients.

No therapeutic ranges linking drug concentrations of apixaban and rivaroxaban to clinical outcomes have been defined. We investigated whether direct oral anticoagulant (DOAC) concentrations among patients admitted to hospital with symptoms of stroke differed between those later verified to suffer an ischemic cerebrovascular event (stroke or transient ischemic attack) and those having other diagnoses (control group). Serum concentrations in 102 patients on DOAC for atrial fibrillation (84%) and thromboembolic disease (16%) were measured within 24 hours of the acute event, employing ultra-high performance liquid chromatography with tandem mass spectrometry. We converted all concentrations to standardized trough levels. DOAC concentrations were lower in the 64 patients with verified ischemic cerebrovascular event than in the 30 controls, 255 ± 155 vs. 329 ± 144 nmol/L (p=0.029), despite no statistically significant difference in self-reported adherence and daily dosages. Calculated concentrations were 5.4-596 nmol/L (median=229 nmol/L) in the ischemic stroke group and 41-602 nmol/L (median=316 nmol/L) in controls. CHA 2 DS 2 -VASc score was significantly higher in the ischemic stroke group than in controls (4.9 ± 1.6 vs. 4.1 ± 1.7; p=0.007). These results may suggest that patients with high cerebrovascular risk might benefit from higher DOAC levels than those with a lower risk.