Real‐world variability in dabigatran levels in patients with atrial fibrillation

• Published in: Journal of thrombosis and haemostasis Vol. 13; no. 3; pp. 353 - 359
• Main Authors: Chan, N. C., Coppens, M., Hirsh, J., Ginsberg, J. S., Weitz, J. I., Vanassche, T., Douketis, J. D., Schulman, S., Eikelboom, J. W.
• Format: Journal Article
• Language: English
• Published: England Elsevier Limited 01.03.2015
• Subjects: Aged; Aged, 80 and over; anticoagulants; Antithrombins - administration & dosage; Antithrombins - adverse effects; Antithrombins - blood; atrial fibrillation; Atrial Fibrillation - blood; Atrial Fibrillation - diagnosis; Atrial Fibrillation - drug therapy; Blood Coagulation - drug effects; blood coagulation test; Blood Coagulation Tests; dabigatran; Dabigatran - administration & dosage; Dabigatran - adverse effects; Dabigatran - blood; Drug Dosage Calculations; Drug Monitoring - methods; Female; Hemorrhage - chemically induced; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Risk Factors; stroke; Time Factors; Treatment Outcome; anticoagulants; dabigatran; atrial fibrillation; blood coagulation test; stroke
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/jth.12823

Summary Background In clinical practice, physicians are given the choice of selecting one of two dabigatran doses based on patient characteristics, with the lower dose typically used in patients at a higher risk of bleeding. Objectives The objectives of the study were to (i) estimate the inter‐ and intra‐patient variability in dabigatran levels with 110 mg (DE110) and 150 mg (DE150) doses, (ii) examine the effect of physicians’ dose selection on levels in DE110 and DE150 subgroups, and (iii) explore whether a single trough measurement identifies patients with extreme levels on subsequent visits. Methods In this prospective observational study of 100 patients with atrial fibrillation (AF), peak and trough levels of dabigatran were measured with the Hemoclot® assay at baseline and every 2 months thereafter (maximum four visits). Results Inter‐patient variability in dabigatran levels (geometric coefficient of variation [gCV], 51–64%) was greater than intra‐patient variability (gCV, 32–40%). Similar medians and distributions of levels were observed in DE110 and DE150 subgroups. Patients receiving DE110 were older, had lower renal function and weighed less than those receiving DE150. Up to 40% of patients whose trough levels were in the upper extremes, and up to 80% of patients whose trough levels were in the lower extremes at baseline, showed subsequent levels that fell in the middle quartiles. Conclusions Our data support the practice of selecting the dabigatran dose based upon clinical characteristics because it results in similar levels of drug exposure in patients given DE110 or DE150. They do not support the concept that a single Hemoclot® measurement reliably identifies patients with consistently high or low values.