Pharmacokinetic robustness of direct oral anticoagulants vs. phenprocoumon in the emergency setting: impact of renal and hepatic impairment.

Abstract

Direct oral anticoagulants (DOACs) are increasingly used, but their pharmacokinetic stability compared to vitamin K antagonists during acute illness remains poorly characterized. We aimed to evaluate the impact of renal and hepatic dysfunction on anticoagulant levels in patients presenting to the emergency department. This multi-center cohort study included 608 patients on established treatment with rivaroxaban, apixaban, dabigatran, edoxaban, or phenprocoumon. Above-threshold anticoagulant levels were determined via drug-specific plasma concentrations, anti-Xa activity, Hemoclot assays, or INR. Multivariable regression was used to assess the impact of renal function and the Model for End-Stage Liver Disease (MELD) score on supratherapeutic levels. Of 608 patients, 457 (75%) received DOACs and 151 (25%) phenprocoumon. Supratherapeutic levels were significantly less frequent with apixaban (14.4%; OR 0.41, 95% CI 0.25-0.69) and edoxaban (10.8%; OR 0.30, 95% CI 0.10-0.90) compared to phenprocoumon (28.5%). Impaired renal function was independently associated with above-threshold levels for DOACs (OR 1.55, 95% CI 1.17-2.05)-particularly apixaban (OR 2.23, 95% CI 1.33-3.75)-but not for phenprocoumon (OR 1.18, 95% CI 0.79-1.76). Conversely, hepatic dysfunction (MELD score) significantly increased the probability of above-threshold levels (OR 3.80, 95% CI 2.78-5.21), with a more pronounced effect on phenprocoumon (OR 5.26, 95% CI 2.86-9.68) than DOACs (OR 3.46, 95% CI 2.44-4.92). DOACs demonstrate superior pharmacokinetic robustness compared to phenprocoumon in the emergency setting. However, DOAC levels are highly sensitive to renal fluctuations, whereas phenprocoumon is more susceptible to hepatic impairment. These findings suggest that individualized monitoring may be necessary for DOAC patients with acute renal decline.