title: Dabigatran Concentration: Variability and Potential Bleeding Prediction In "Real-Life" Patients With Atrial Fibrillation.
abstract: Routine laboratory monitoring is currently not recommended in patients receiving dabigatran despite its considerable variation in plasma concentration. However, in certain clinical situations, measurements of the dabigatran effect may be desirable. We aimed to assess the variability of dabigatran trough and peak concentration and explore the potential relationship between dabigatran concentration and adverse events. We included 44 patients with atrial fibrillation who started treatment with dabigatran 150 mg (D150) or 110 mg (D110) twice daily. They contributed 170 trough and peak blood samples that were collected 2-4 and 6-8 weeks after dabigatran initiation. Plasma dabigatran concentration was measured by LC-MS/MS and indirectly, by selected coagulation tests. D110 patients were older (74 ± 7 versus 68 ± 6 years), had lower creatinine clearance (68 ± 21 versus 92 ± 24 mL/min) and higher CHA2 DS2 -VASc score (3.1 ± 1.3 versus 2.3 ± 0.9) compared to D150 patients (all p < 0.05), but both had similar dabigatran concentrations in both trough and peak samples. Dabigatran concentrations varied less in trough than in peak samples (17.0 ± 13.6 versus 26.6 ± 19.2%, p = 0.02). During the 12-month follow-up, 4 patients on D150 and 6 on D110 suffered minor bleeding. There was no major bleeding or thromboembolic event. Patients with bleeding had significantly higher average trough dabigatran concentrations (93 ± 36 versus 72 ± 62 μg/L, p = 0.02) than patients without bleeding, while peak dabigatran values had no predictive value. Dabigatran dose selection according to the guidelines resulted in appropriate trough concentrations with acceptable repeatability. High trough concentrations may predispose patients to the risk of minor bleeding.
authors.affiliation: Department of Vascular Diseases, University Medical Centre, Ljubljana, Slovenia.
authors.forename: Petra
authors.initials: P
authors.lastname: Šinigoj
authors.affiliation: Department of Medicine Solna, Karolinska Institutet & Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Rickard E
authors.initials: RE
authors.lastname: Malmström
authors.affiliation: Department of Vascular Diseases, University Medical Centre, Ljubljana, Slovenia.
authors.forename: Nina
authors.initials: N
authors.lastname: Vene
authors.affiliation: Department of Laboratory Medicine Huddinge, Division of Clinical Pharmacology, Karolinska Institutet & Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Rönquist-Nii
authors.affiliation: Department of Vascular Diseases, University Medical Centre, Ljubljana, Slovenia.
authors.forename: Mojca
authors.initials: M
authors.lastname: Božič-Mijovski
authors.affiliation: Department of Laboratory Medicine Huddinge, Division of Clinical Pharmacology, Karolinska Institutet & Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anton
authors.initials: A
authors.lastname: Pohanka
authors.affiliation: Department of Coagulation Research, Institute for Molecular Medicine and Surgery, Karolinska Institutet & Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jovan P
authors.initials: JP
authors.lastname: Antovic
authors.affiliation: Department of Vascular Diseases, University Medical Centre, Ljubljana, Slovenia.
authors.forename: Alenka
authors.initials: A
authors.lastname: Mavri
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000009:adverse effects* / Q000097:blood*; D001281:Atrial Fibrillation / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D002853:Chromatography, Liquid; D000069604:Dabigatran / Q000009:adverse effects* / Q000097:blood*; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000991:Antithrombins; D000069604:Dabigatran