Practical issues on DOAC treatment

Currently the four direct oral anticoagulants (DOAC) Apixaban, Dabigatran, Edoxaban and Rivaroxaban are approved in Switzerland for the following indications: prevention of stroke or systemic embolism in non-valvular atrial fibrillation and treatment of venous thromboembolism. Moreover, Apixaban and Rivaroxaban are approved for thromboprophylaxis after orthopedic hip-and knee surgery. The dosage is once or twice daily, depending on the indication and type of DOAC. With exeption of Rivaroxaban in therapeutic dose, they can be taken irrespective of food ingestion. In some situations the dosage has to be adjusted in case of age >80 years, low body weight and/or renal impairment. The DOAC are metabolized by the enzymes CYP3A4 and/or p-glycoprotein. Strong inhibitors (e.g. azoles, protease-inhibitors) and inductors (e.g. rifampicin, phenytoin, carbamazepine) of these enzymes can prolong respectively reduce the anticoagulatory effect. Therefore an interaction check is warranted before prescription. DOAC are contraindicated during pregnancy and lactation. Women with childbearing potential have to use an effective contraception. Sporting activity without high bleeding risk can be feasible under some precautions. Physicians must be aware that DOAC influence many of the frequently used coagulation tests. In particular the prothrombin time will be prolonged according to the elimination half-life. Diagnostic and therapeutic algorithms can be applied to manage bleeding complications. Currently, idarucizumab is available in a compassionate use programm to reverse the anticoagulant effect of dabigatran. Andexanet is a specific antidote of factor-Xa-inhibitors which is currently investigated in phase-III-trials and for which the approval is expected.