Marko Miklič1, Alenka Mavri2, Nina Vene1, Lisbeth Söderblom3, Mojca Božič-Mijovski1, Anton Pohanka4, Jovan Antovic3, Rickard E Malmström5. 1. Department of Vascular Diseases, University Medical Centre Ljubljana, Zaloška 2, SI-1000, Ljubljana, Slovenia. 2. Department of Vascular Diseases, University Medical Centre Ljubljana, Zaloška 2, SI-1000, Ljubljana, Slovenia. alenka.mavri@kclj.si. 3. Department of Coagulation Research, Institute for Molecular Medicine and Surgery, Karolinska Institutet, & Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden. 4. Department of Laboratory Medicine Huddinge, Division of Clinical Pharmacology, Karolinska Institutet & Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden. 5. Department of Medicine Solna, Karolinska Institutet & Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden.
Abstract
BACKGROUND: Routine laboratory monitoring of rivaroxaban and dose adjustment relating to exposure is currently not recommended. However, in certain clinical situations, assessment of rivaroxaban levels is desirable. OBJECTIVES: To examine inter- and intra-subject plasma rivaroxaban variability in patients with atrial fibrillation (AF) and to correlate these results to clinical outcomes. PATIENTS/ METHODS: We included 60 patients with AF treated with rivaroxaban: half on 20 mg daily (R20) and half on 15 mg daily (R15). Three trough and peak blood samples were collected with an interval of 6-8 weeks apart. Plasma rivaroxaban concentration was measured directly by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) and indirectly by anti-Xa for rivaroxaban, prothrombin time (PT), and activated partial thromboplastin time (APTT). RESULTS: Patients on R15 were older (76 ± 6 vs 71 ± 6 years), had lower creatinine clearance (60 ± 26 vs 99 ± 32 mL/min), higher CHADS2 (2.5 ± 1.2 vs 1.8 ± 1.3), all p < 0.01, but had similar rivaroxaban concentrations in trough samples to patients on R20. There was no significant intra-individual variability for trough or peak rivaroxaban concentration assessed by LC-MS/MS, anti-Xa, or PT. Trough rivaroxaban levels determined by LC-MS/MS (48 ± 30 vs 34 ± 26, p = 0.02) and anti-Xa, but not with PT and APTT, were higher in patients with bleeding than in patients without it. CONCLUSIONS: There is a pronounced inter-, but not intra-individual variability in the rivaroxaban trough levels in patients with AF. Assessment of trough rivaroxaban concentration with LC-MS/MS or anti-Xa, but not with APTT or PT, may help to identify patients at increased risk of bleeding.
BACKGROUND: Routine laboratory monitoring of rivaroxaban and dose adjustment relating to exposure is currently not recommended. However, in certain clinical situations, assessment of rivaroxaban levels is desirable. OBJECTIVES: To examine inter- and intra-subject plasma rivaroxaban variability in patients with atrial fibrillation (AF) and to correlate these results to clinical outcomes. PATIENTS/ METHODS: We included 60 patients with AF treated with rivaroxaban: half on 20 mg daily (R20) and half on 15 mg daily (R15). Three trough and peak blood samples were collected with an interval of 6-8 weeks apart. Plasma rivaroxaban concentration was measured directly by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) and indirectly by anti-Xa for rivaroxaban, prothrombin time (PT), and activated partial thromboplastin time (APTT). RESULTS:Patients on R15 were older (76 ± 6 vs 71 ± 6 years), had lower creatinine clearance (60 ± 26 vs 99 ± 32 mL/min), higher CHADS2 (2.5 ± 1.2 vs 1.8 ± 1.3), all p < 0.01, but had similar rivaroxaban concentrations in trough samples to patients on R20. There was no significant intra-individual variability for trough or peak rivaroxaban concentration assessed by LC-MS/MS, anti-Xa, or PT. Trough rivaroxaban levels determined by LC-MS/MS (48 ± 30 vs 34 ± 26, p = 0.02) and anti-Xa, but not with PT and APTT, were higher in patients with bleeding than in patients without it. CONCLUSIONS: There is a pronounced inter-, but not intra-individual variability in the rivaroxaban trough levels in patients with AF. Assessment of trough rivaroxaban concentration with LC-MS/MS or anti-Xa, but not with APTT or PT, may help to identify patients at increased risk of bleeding.
Entities:
Keywords:
Anti-Xa assay; Atrial fibrillation; Drug monitoring; LC-MS/MS; Rivaroxaban
Authors: Jurjen S Kingma; Desirée M T Burgers; Valerie M Monpellier; Marinus J Wiezer; Heleen J Blussé van Oud-Alblas; Janelle D Vaughns; Catherine M T Sherwin; Catherijne A J Knibbe Journal: Br J Clin Pharmacol Date: 2021-06-03 Impact factor: 3.716
Authors: D A Sychev; O A Baturina; K B Mirzaev; E Rytkin; D V Ivashchenko; D A Andreev; K A Ryzhikova; E A Grishina; P O Bochkov; R V Shevchenko Journal: Pharmgenomics Pers Med Date: 2020-01-23