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Rivaroxaban and apixaban in orthopaedics: is there a difference in their plasma concentrations and anticoagulant effects?

Freyburger G, Macouillard G, Khennoufa K, Labrouche S, Molimard M, Sztark F - Blood Coagul. Fibrinolysis (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: aLaboratory of Hematology bDepartment of Anesthesiology cLaboratory of Clinical Pharmacology, Bordeaux University Hospital, Bordeaux, France.

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.

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Related in: MedlinePlus

Rivaroxaban and apixaban plasma concentrations as measured by using mass spectrometry according to withdrawal time grouped into five periods of time from T0 to T4. The bold lines represent the mean values and SDs.
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Figure 1: Rivaroxaban and apixaban plasma concentrations as measured by using mass spectrometry according to withdrawal time grouped into five periods of time from T0 to T4. The bold lines represent the mean values and SDs.

Mentions: Figure 1 shows rivaroxaban and apixaban plasma concentrations measured by using LC-MS/MS according to withdrawal time. The Ctrough summarized at T4 (Fig. 1a and b) include data from D6 to D10. Residual concentrations were very low in all patients receiving rivaroxaban, except in one who was not an outlier at the other sampling times during his hospital stay (see the dotted line). On the contrary, residual apixaban concentrations were closer to the peak concentrations than those of rivaroxaban. The peak concentrations from T1 to T3 were highly variable among the patients and also in a given patient. The mean peak concentration at T1 was lower than the peak concentrations in the following periods, so steady state was not attained before day 4.


Rivaroxaban and apixaban in orthopaedics: is there a difference in their plasma concentrations and anticoagulant effects?

Freyburger G, Macouillard G, Khennoufa K, Labrouche S, Molimard M, Sztark F - Blood Coagul. Fibrinolysis (2015)

Rivaroxaban and apixaban plasma concentrations as measured by using mass spectrometry according to withdrawal time grouped into five periods of time from T0 to T4. The bold lines represent the mean values and SDs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664024&req=5

Figure 1: Rivaroxaban and apixaban plasma concentrations as measured by using mass spectrometry according to withdrawal time grouped into five periods of time from T0 to T4. The bold lines represent the mean values and SDs.
Mentions: Figure 1 shows rivaroxaban and apixaban plasma concentrations measured by using LC-MS/MS according to withdrawal time. The Ctrough summarized at T4 (Fig. 1a and b) include data from D6 to D10. Residual concentrations were very low in all patients receiving rivaroxaban, except in one who was not an outlier at the other sampling times during his hospital stay (see the dotted line). On the contrary, residual apixaban concentrations were closer to the peak concentrations than those of rivaroxaban. The peak concentrations from T1 to T3 were highly variable among the patients and also in a given patient. The mean peak concentration at T1 was lower than the peak concentrations in the following periods, so steady state was not attained before day 4.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: aLaboratory of Hematology bDepartment of Anesthesiology cLaboratory of Clinical Pharmacology, Bordeaux University Hospital, Bordeaux, France.

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.

Show MeSH
Related in: MedlinePlus