Abstract 11598: Is Therapeutic Drug Monitoring of Direct Anticoagulants Really Unnecessary?

Abstract

Introduction: no routine monitoring is deemed necessary with direct oral anticoagulants dabigatran (D) and rivaroxaban(R). Yet, their misuse may lead to inefficacy or increased risk of bleeding. Hypothesis: due to the prevalence of elderly patients in our medical center, the pharmacology department was asked to measure R and D plasma concentrations. Therefore we aimed not only to check their prescription adequacy but also to evaluate whether bleeding or thrombosis adverse events were associated with drug concentrations clearly outside of their expected “normal” range. Methods: Patients receiving R or D for either AFib, deep venous thrombosis or its prevention were included and had blood samples drawn for drug measurements, by HPLC-tandem mass spectrometry. Adequacy of the patient prescription was checked by pharmacists according D & R respective SmPCs. A robust and conservative method was applied to evaluate anticoagulant concentrations : D & R concentrations were blindly deemed “normal” when within the [IC] 95 limits (peak and trough, relative to the dose) observed in the respective RE-LY and Rocket-AF pivotal studies, as compared to “out of range” when outside of these limits. Results: 287 consecutive patients from our center had their concentration of R (n=219 : 76%) or D (n = 68 : 24%) measured. The inadequacy of the prescriptions was 31.4% alltogether. Seventy patients presented with bleeding (n = 48, 17%) or thrombosis (n = 22, 8%), that either led to their admission in emergency, or occurred in the hospital wards. Bleedings and thrombosis were significantly associated with out-of-range concentrations (p<0.01). Patients with hemorrhages had higher concentrations (R: 194 VS 83 μg.l -1 and D: 128 VS 80 μg.l -1 ) whereas thrombosis were associated with lower ones (R: 75 VS 106 μg.l -1 D: 29 VS 93 μg.l -1 ). HAS-BLED Score was 2.0 ± 0.9 for bleeding cases as compared to 1.5 ± 0.9 (p<0.01). Conclusions: therapeutic drug monitoring of direct oral anticoagulants might not be superfluous, at least for R & D, especially in patients with a higher score HAS-BLED.