Rivaroxaban and apixaban in orthopaedics

Abstract

The aim of this study was to improve knowledge of what happens in the coagulation of orthopaedic patients under rivaroxaban and apixaban, in order to finalize and cross-validate effective measurement methods and to provide arguments for helping to reference one or the other drug in our central pharmacy. One hundred and two patients undergoing total hip or knee replacement were included. Half of them received rivaroxaban and the other half received apixaban. Blood samples (n = 244 with each drug) were taken at Cmax preoperatively and twice a week, apart from the day of the patient's discharge, when Ctrough concentration was targeted. Routine coagulation parameters, and functional and liquid chromatography tandem mass spectrometry assays for measurement of circulating concentrations were studied. The LC-MS/MS assay and the functional assays carried out in patients under routine conditions were highly correlated, apart from low concentrations (<30 ng/ml), which were affected by the variable individual potential to inhibit the exogenous bovine Xa used in the functional assays. After 1 week of treatment, the drugs differed: Cmax and Ctrough were closer when apixaban was taken twice daily (83 ± 39 and 58 ± 17 ng/ml) than with rivaroxaban taken once a day (113 ± 67 and 13 ± 20 ng/ml). Rivaroxaban had a greater influence on routine coagulation tests and reduced the maximum thrombin concentration more efficiently, as assessed by the thrombin generation test. Although rivaroxaban and apixaban present apparently similar constant rates, they exhibit significant differences in their concentrations and anticoagulant effects when studied ex vivo in orthopedic patients.

Effects of thromboprophylactic doses of apixaban and rivaroxaban on coagulation and thrombin generation in association with total hip replacement

“…Mean apixaban concentration at our study at the peak level varied by eightfold, and rivaroxaban only by 1.5-fold, while in the phase III studies, a fourfold peak for apixaban and a 40-fold peak for rivaroxaban were observed. Our findings in orthopaedic patient population confirm the previous comparison of apixaban and rivaroxaban [19]; both markedly affected thrombin-generation variables in vitro, while F1 + 2 were stable in vivo. As ETP and peak correlated, and are both known to associate with VTE [20], we decided to focus on the ETP results.…”

Recommendations from the ICM-VTE: General

“…However, a qualitative assessment PT; aPPT; thromboelastography, and rotational thromboelastography) are not reliable for monitoring rivaroxaban, apixaban, edoxaban due to the complexity of standardization related to the large number of reagent variants used and the variability of results among patients 1911 . This is also demonstrated by studies involving patients after orthopedic interventions 1914,1915 .…”

“…Rivaroxaban and apixaban have different effects on the coagulometric measurements of patients after THA and TKA. Freyburger et al, found that rivaroxaban resulted in a higher increase of antithrombin levels, aPTT, PT and D-dimer compared to apixaban 1914 . Also, rivaroxaban more pronouncedly reduced the concentration of thrombin (thrombin generation test) than apixaban 1914,1916 .…”

“…Freyburger et al, found that rivaroxaban resulted in a higher increase of antithrombin levels, aPTT, PT and D-dimer compared to apixaban 1914 . Also, rivaroxaban more pronouncedly reduced the concentration of thrombin (thrombin generation test) than apixaban 1914,1916 . Fuji et al, showed the dependence of the blood concentration of edoxaban in 264 patients after THA on PT, INR, and aPTT 1921 .…”

Optimization of the Extraction Procedure of Apixaban from Dried Rat Plasma Spots

“…Their advantages are wide therapeutic index, fixed dose regimen, favorable efficacy/safety ratio, and minor drug−drug and drug−food interactions [6]. For example, apixaban is a selective inhibitor of blood clotting human factor-Xa [7,8]. It is also used to treat deep veins and pulmonary embolism and to prevent their recurrence [9].…”