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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

(a) On the left, a linear regression model fitted using the least square approach shows the relationship between the two methods for Xabans concentrations (black circles for rivaroxaban and gray circles for apixaban): mass spectrometry (LC-MS/MS) on the X-axis and the functional anti-Xa tests on the Y-axis. (b) On the right, the histograms represent the arithmetic mean values and SDs of concentrations obtained with both drugs by mass spectrometry and by the anti-Xa functional assays at the different periods. Black solid bars (▪ LC-MS/MS) and black hatched (  anti-Xa) bars represent the results from rivaroxaban-treated patients. Gray solid (  LC-MS/MS) and gray hatched (  anti-Xa) bars represent the results from apixaban-treated patients. ∗ when significant (Student's t-test P < 0.05).
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Figure 2: (a) On the left, a linear regression model fitted using the least square approach shows the relationship between the two methods for Xabans concentrations (black circles for rivaroxaban and gray circles for apixaban): mass spectrometry (LC-MS/MS) on the X-axis and the functional anti-Xa tests on the Y-axis. (b) On the right, the histograms represent the arithmetic mean values and SDs of concentrations obtained with both drugs by mass spectrometry and by the anti-Xa functional assays at the different periods. Black solid bars (▪ LC-MS/MS) and black hatched (  anti-Xa) bars represent the results from rivaroxaban-treated patients. Gray solid (  LC-MS/MS) and gray hatched (  anti-Xa) bars represent the results from apixaban-treated patients. ∗ when significant (Student's t-test P < 0.05).

Mentions: Similar graphs were obtained by using the functional anti-Xa assay (data not shown). Figure 2a illustrates the good correlation between mass spectrometry and anti-Xa results, with r values higher than 0.900. Results were very similar with both methods, although the paired Student's test showed a significant difference between functional and physical assays for apixaban at T1 and T4, in which case the mean values were 20 versus 30 and 48 versus 56 ng/ml, respectively – a difference which is not clinically relevant.


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)

(a) On the left, a linear regression model fitted using the least square approach shows the relationship between the two methods for Xabans concentrations (black circles for rivaroxaban and gray circles for apixaban): mass spectrometry (LC-MS/MS) on the X-axis and the functional anti-Xa tests on the Y-axis. (b) On the right, the histograms represent the arithmetic mean values and SDs of concentrations obtained with both drugs by mass spectrometry and by the anti-Xa functional assays at the different periods. Black solid bars (▪ LC-MS/MS) and black hatched (  anti-Xa) bars represent the results from rivaroxaban-treated patients. Gray solid (  LC-MS/MS) and gray hatched (  anti-Xa) bars represent the results from apixaban-treated patients. ∗ when significant (Student's t-test P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: (a) On the left, a linear regression model fitted using the least square approach shows the relationship between the two methods for Xabans concentrations (black circles for rivaroxaban and gray circles for apixaban): mass spectrometry (LC-MS/MS) on the X-axis and the functional anti-Xa tests on the Y-axis. (b) On the right, the histograms represent the arithmetic mean values and SDs of concentrations obtained with both drugs by mass spectrometry and by the anti-Xa functional assays at the different periods. Black solid bars (▪ LC-MS/MS) and black hatched (  anti-Xa) bars represent the results from rivaroxaban-treated patients. Gray solid (  LC-MS/MS) and gray hatched (  anti-Xa) bars represent the results from apixaban-treated patients. ∗ when significant (Student's t-test P < 0.05).
Mentions: Similar graphs were obtained by using the functional anti-Xa assay (data not shown). Figure 2a illustrates the good correlation between mass spectrometry and anti-Xa results, with r values higher than 0.900. Results were very similar with both methods, although the paired Student's test showed a significant difference between functional and physical assays for apixaban at T1 and T4, in which case the mean values were 20 versus 30 and 48 versus 56 ng/ml, respectively – a difference which is not clinically relevant.

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