Therapeutic monitoring of direct oral anticoagulants — an 8-year observational study

Introduction: For years, anticoagulants have been the basic group of drugs that slow down, inhibit or prevent blood clotting by inhibiting thrombin formation or reducing its activity. Treatment with DOACs does not require routine anticoagulation monitoring due to their wide therapeutic index. However, there are circumstances where it may be necessary to know the drug levels to manage the risk of side effects or to confirm laboratory efficacy. In such a situation, an indication for DOAC laboratory testing could be the suspicion of excessively high or low DOAC levels. The aim of this article was to determine trends in concentrations of DOACs in a real life population of patients. Material and methods: Consultations in clinical pharmacology extended with DOAC level assessments were performer in the Department of Cardiology and Clinical Pharmacology. The trial was designed as a retrospective analysis of laboratory analyses and included 480 laboratory tests performed in 236 patients. Results: Mean CHA 2 DS 2- VASc scoring 3.91 ±1.92 and HAS-BLED scoring 3.57 ±1.75 indicated high risks of both thrombosis and bleeding. Geometric mean of trough concentrations for dabigatran, rivaroxaban and apixaban were 91.53 ng/mL, 62.74 ng/mL and 124.81 ng/mL, whereas peak concentrations for all DOACs were significantly higher, at 220.80 ng/mL ( p < 0.0001), 116.59 ng/mL ( p < 0.0001) and 186.18 ng/mL ( p =0.0354), respectively. Values for males and females did not differ significantly. Dose adjustment, performed according to rules described for every drug in registered drug characteristics, did not change significantly concentrations. Trough concentrations higher than 20 ng/mL were found at the 10 th percentile for all DOACs, but higher at 40 ng/mL at the 5 th percentile was found only for apixaban. Peak concentration lower than 400 ng/mL were for the 95 th percentile for apixaban and for the 90 th percentile for dabigatran and rivaroxaban. Conclusion: Monitoring-based pharmacotherapy with DOACs should be restricted only to specific clinical settings; in the general population, it is not necessary. Recently, in many experienced centers, therapeutic drug monitoring of DOACs has gained great importance in selected clinical settings and it very likely will soon become commonplace in clinical practice.