The association between direct oral anticoagulant concentration upon acute stroke and stroke outcome

Abstract

Background: This study aimed to investigate the association between direct oral anticoagulant (DOAC) concentration upon acute ischemic stroke (IS) or intracranial hemorrhage (ICH) and stroke outcomes.

Methods: Patients aged ≥20 years treated with DOACs, including dabigatran, rivaroxaban, apixaban, or edoxaban, and developed acute IS or ICH were enrolled to measure DOAC concentration at the time of hospital presentation by using ultrahigh-performance liquid chromatography with tandem mass spectrometry. Ischemic stroke patients was categorized into low (<50 ng/mL) and effective (≥50 ng/mL) groups. The primary outcome was poor functional outcomes at 3 months (modified Rankin Scale scores of 4-6).

Results: A total of 138 patients were enrolled, including 105 IS (76.1%) and 33 ICH patients. In the IS cohort, the average DOAC concentration was 85.7 ± 88.6 ng/mL (low DOAC concentration: 42.9%). Low level group had numerically higher NIHSS (14 versus 9, p = 0.37), significantly poorer functional outcomes at 3 months (odds ratio [OR], 5.08 [1.32, 19.63]), and higher chance of stroke-in-evolution (OR, 6.83 [1.64, 28.41]). In the ICH cohort, the average DOAC concentration was 128.9 ± 111.9 ng/mL. Reversal therapy was administered in 60.6% of patients. Hematoma growth occurred in 35.7% patients. The DOAC concentration was similar across patients with or without reversal therapy, and with or without hematoma growth.

Conclusion: Among DOAC users who developed IS, low drug concentrations at hospital presentation predicted poor outcomes.

Keywords: Direct oral anticoagulants; Drug monitoring; Intracranial hemorrhage; Ischemic stroke.