Real-life peak and trough dabigatran plasma measurements over time in hospitalized geriatric patients with atrial fibrillation
Few geriatric patients were included in studies on direct oral anticoagulants and data on dabigatran concentration and safety are needed in this population. Our objectives were to evaluate peak and trough dabigatran plasma concentrations over time in a geriatric population and to identify factors associated with dabigatran plasma concentrations and to assess the relationship with bleeding events.
Peak and trough dabigatran plasma concentration were performed 4,8,15,30,45 days after inception of dabigatran treatment in 68 consecutive patients≥75 years old hospitalized in a geriatric hospital with atrial fibrillation. Bleeding events were monitored for 1 year.
Mean age was 85.8(5.1) years old and 76.5% were women. Overall, 541 dabigatran plasma measurements (270 peak, 271 trough) were performed. Mean dabigatran concentrations of the 5 sequential measurements ranged 106-146ng/mL for peak and 66-84ng/mL for trough. Renal failure was associated with high peak and trough dabigatran concentration. Inter- and intra-individual coefficients of variation were 59.5% and 44.7% for peak and 74.5% and 44.6% for trough. Participants in the lower two tertiles of dabigatran concentration at day 8 (D8) remained below the 90th percentile (243.9ng/ml) on the next measurements. Bleeding events were associated with high trough dabigatran concentrations. Trough dabigatran concentration at D8>243.9ng/mL significantly predicted bleeding.
In this geriatric population, renal function and low albumin were associated with dabigatran concentrations. Despite large variability, participants in the lower two tertiles of dabigatran concentration at D8 remained below the 90th percentile on the following measurements. D8 dabigatran trough concentration≥243.9ng/mL identified patients at risk of bleeding.
Key wordsAnticoagulants antithrombins atrial fibrillation aged 80 and over
- 2.Fuster V, Ryden LE, Cannom DS et al. ACC/AHA/ESC 2006. Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001. Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006;114:e257–354.CrossRefPubMedGoogle Scholar
- 10.Sharma M, Cornelius VR, Patel JP, Davies JG, Molokhia M. Efficacy and Harms of Direct Oral Anticoagulants in the Elderly for Stroke Prevention in Atrial Fibrillation and Secondary Prevention of Venous Thromboembolism: Systematic Review and Meta-Analysis. Circulation. 2015;132:194–204.CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Eikelboom JW, Wallentin L, Connolly SJ et al. Risk of bleeding with 2. doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011;123:2363–72.CrossRefPubMedGoogle Scholar
- 21.Reilly PA, Lehr T, Haertter S et al. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol. 2014;63:321–8.CrossRefPubMedGoogle Scholar
- 29.Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener H, Joyner CD, Wallentin L. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.CrossRefPubMedGoogle Scholar
- 31.European Medicines Agency. Pradaxa Summary of Product Characteristics. European Medicines Agency. 2013.Google Scholar
- 35.FDA. Summary Review for Pradaxa. 2010.Google Scholar