Antithrombotics' Therapeutic Optimization in Hospitalized Patients Using Physiologically- and Population-based Pharmacokinetic Modeling

Patients treated with antithrombotics are at risk of both severe ischemic and bleeding events. However, current clinical scores are insufficiently discriminant to predict the most favorable drug and dosing for an improved net clinical benefit. Physiologically and population-based pharmacokinetic models (PBPK and POPPK respectively) incorporate substrate specific properties obtained from experimental in-vitro experiments as well as patients' demographic, genetic and physiological in vivo data in order to characterize the dose-concentration relationships. As such, they can be used to simulate and predict PK profiles accounting for specific patients' characteristics and are the basis of dosing optimization. These models could be a valuable tool to predict antithrombotic blood concentration in a given patient. Our main goal is to elaborate predictive models characterizing the dose-concentration relationship with influencing variables of three direct oral anticoagulants (DOAC) (rivaroxaban, apixaban, dabigatran) and three P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) in hospitalized patients, which will serve as basis for drug selection and dosage optimization.

Inclusion criteria

• Hospitalized patients at any of the Geneva University Hospitals 18 yo and older
• Treated with DOAC (dabigatran, rivaroxaban, apixaban) or/and P2Y12 (clopidogrel, ticragrelor et prasugel) at the time of study blood sampling
• Understanding of French language and able to give an inform consent.

Exclusion criteria

• Patients with a reduced life span (<6 mois)
• Exclusion criteria during follow up
• Change in dosage or cessation of the DOAC or P2Y12 taken by the participant follow up data will be censored at the time of change.