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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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(a) Activated partial thromboplastin time (aPTT) and prothrombin time (PT) evolution (mean and SD) according to the time of withdrawal in rivaroxaban (black circles) and apixaban (gray circles)-treated patients. Wilcoxon test significance (changes between two successive times in rivaroxaban or apixaban-treated patients) is represented by horizontal stars (∗∗P < 0.001, ∗∗∗P < 0.0001), whereas Mann–Whitney test significance (rivaroxaban versus apixaban treatment at each time) is represented by shaded vertical stars ( P < 0.0001). On the right, aPTT (b) and PT (d) correlations with rivaroxaban (black circles) and apixaban (grey circles) as measured by mass spectrometry. Best fitting results from a power function (y = a × xb), that is, a linear function between the log-transformed PT or aPTT values and the untransformed Xabans concentrations. ∗<0.025, ∗∗≤0.001, ∗∗∗ < 0.0001.
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Figure 3: (a) Activated partial thromboplastin time (aPTT) and prothrombin time (PT) evolution (mean and SD) according to the time of withdrawal in rivaroxaban (black circles) and apixaban (gray circles)-treated patients. Wilcoxon test significance (changes between two successive times in rivaroxaban or apixaban-treated patients) is represented by horizontal stars (∗∗P < 0.001, ∗∗∗P < 0.0001), whereas Mann–Whitney test significance (rivaroxaban versus apixaban treatment at each time) is represented by shaded vertical stars ( P < 0.0001). On the right, aPTT (b) and PT (d) correlations with rivaroxaban (black circles) and apixaban (grey circles) as measured by mass spectrometry. Best fitting results from a power function (y = a × xb), that is, a linear function between the log-transformed PT or aPTT values and the untransformed Xabans concentrations. ∗<0.025, ∗∗≤0.001, ∗∗∗ < 0.0001.

Mentions: Figure 3 illustrates the relative sensitivity of PT and aPTT to both drugs according to the time of withdrawal.


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) Activated partial thromboplastin time (aPTT) and prothrombin time (PT) evolution (mean and SD) according to the time of withdrawal in rivaroxaban (black circles) and apixaban (gray circles)-treated patients. Wilcoxon test significance (changes between two successive times in rivaroxaban or apixaban-treated patients) is represented by horizontal stars (∗∗P < 0.001, ∗∗∗P < 0.0001), whereas Mann–Whitney test significance (rivaroxaban versus apixaban treatment at each time) is represented by shaded vertical stars ( P < 0.0001). On the right, aPTT (b) and PT (d) correlations with rivaroxaban (black circles) and apixaban (grey circles) as measured by mass spectrometry. Best fitting results from a power function (y = a × xb), that is, a linear function between the log-transformed PT or aPTT values and the untransformed Xabans concentrations. ∗<0.025, ∗∗≤0.001, ∗∗∗ < 0.0001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: (a) Activated partial thromboplastin time (aPTT) and prothrombin time (PT) evolution (mean and SD) according to the time of withdrawal in rivaroxaban (black circles) and apixaban (gray circles)-treated patients. Wilcoxon test significance (changes between two successive times in rivaroxaban or apixaban-treated patients) is represented by horizontal stars (∗∗P < 0.001, ∗∗∗P < 0.0001), whereas Mann–Whitney test significance (rivaroxaban versus apixaban treatment at each time) is represented by shaded vertical stars ( P < 0.0001). On the right, aPTT (b) and PT (d) correlations with rivaroxaban (black circles) and apixaban (grey circles) as measured by mass spectrometry. Best fitting results from a power function (y = a × xb), that is, a linear function between the log-transformed PT or aPTT values and the untransformed Xabans concentrations. ∗<0.025, ∗∗≤0.001, ∗∗∗ < 0.0001.
Mentions: Figure 3 illustrates the relative sensitivity of PT and aPTT to both drugs according to the time of withdrawal.

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