Skip to main content
Erschienen in: The journal of nutrition, health & aging 1/2018

14.10.2017

Real-Life Peak and Trough Dabigatran Plasma Measurements Over Time in Hospitalized Geriatric Patients with Atrial Fibrillation

verfasst von: E. Chaussade, Olivier Hanon, C. Boully, F. Labourée, L. Caillard, G. Gerotziafas, J.-S. Vidal, I. Elalamy

Erschienen in: The journal of nutrition, health & aging | Ausgabe 1/2018

Einloggen, um Zugang zu erhalten

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.
Literatur
1.
Zurück zum Zitat Heeringa J, van der Kuip DAM, Hofman A et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J. 2006;27:949–53.CrossRefPubMed Heeringa J, van der Kuip DAM, Hofman A et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J. 2006;27:949–53.CrossRefPubMed
2.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
3.
Zurück zum Zitat Hanon O, Assayag P, Belmin J et al. Expert consensus of the French Society of Geriatrics and Gerontology and the French Society of Cardiology on the management of atrial fibrillation in elderly people. Arch Cardiovasc Dis. 2013;106:303–23.CrossRefPubMed Hanon O, Assayag P, Belmin J et al. Expert consensus of the French Society of Geriatrics and Gerontology and the French Society of Cardiology on the management of atrial fibrillation in elderly people. Arch Cardiovasc Dis. 2013;106:303–23.CrossRefPubMed
4.
Zurück zum Zitat Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146:857–67.CrossRefPubMed Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146:857–67.CrossRefPubMed
5.
Zurück zum Zitat Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011;365:2002–12.CrossRefPubMed Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011;365:2002–12.CrossRefPubMed
6.
Zurück zum Zitat Peterson GM, Boom K, Jackson SL, Vial JH. Doctors’ beliefs on the use of antithrombotic therapy in atrial fibrillation: identifying barriers to stroke prevention. Intern Med J. 2002;32:15–23.CrossRefPubMed Peterson GM, Boom K, Jackson SL, Vial JH. Doctors’ beliefs on the use of antithrombotic therapy in atrial fibrillation: identifying barriers to stroke prevention. Intern Med J. 2002;32:15–23.CrossRefPubMed
7.
Zurück zum Zitat Hanon O, Vidal JS, Pisica-Donose G et al. Therapeutic management in ambulatory elderly patients with atrial fibrillation: the S.AGES cohort. J Nutr Health Aging. 2015;19:219–27.CrossRefPubMed Hanon O, Vidal JS, Pisica-Donose G et al. Therapeutic management in ambulatory elderly patients with atrial fibrillation: the S.AGES cohort. J Nutr Health Aging. 2015;19:219–27.CrossRefPubMed
8.
Zurück zum Zitat Ogilvie IM, Newton N, Welner SA, Cowell W, Lip GYH. Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med. 2010;123:638–645.e4.CrossRefPubMed Ogilvie IM, Newton N, Welner SA, Cowell W, Lip GYH. Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med. 2010;123:638–645.e4.CrossRefPubMed
9.
Zurück zum Zitat Ruff CT, Giugliano RP, Braunwald E et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a metaanalysis of randomised trials. Lancet. 2014;383:955–62.CrossRefPubMed Ruff CT, Giugliano RP, Braunwald E et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a metaanalysis of randomised trials. Lancet. 2014;383:955–62.CrossRefPubMed
10.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Sardar P, Chatterjee S, Lavie CJ et al. Risk of major bleeding in different indications for new oral anticoagulants: insights from a meta-analysis of approved dosages from 50. randomized trials. Int J Cardiol. 2015;179:279–87.CrossRefPubMed Sardar P, Chatterjee S, Lavie CJ et al. Risk of major bleeding in different indications for new oral anticoagulants: insights from a meta-analysis of approved dosages from 50. randomized trials. Int J Cardiol. 2015;179:279–87.CrossRefPubMed
12.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
14.
Zurück zum Zitat Muhlberg W, Platt D. Age-dependent changes of the kidneys: pharmacological implications. Gerontology. 1999;45:243–53.CrossRefPubMed Muhlberg W, Platt D. Age-dependent changes of the kidneys: pharmacological implications. Gerontology. 1999;45:243–53.CrossRefPubMed
15.
Zurück zum Zitat Burton DGA, Allen MC, Bird JLE, Faragher RGA. Bridging the gap: ageing, pharmacokinetics and pharmacodynamics. J Pharm Pharmacol. 2005;57:671–9.CrossRefPubMed Burton DGA, Allen MC, Bird JLE, Faragher RGA. Bridging the gap: ageing, pharmacokinetics and pharmacodynamics. J Pharm Pharmacol. 2005;57:671–9.CrossRefPubMed
17.
Zurück zum Zitat Deedwania PC. New oral anticoagulants in elderly patients with atrial fibrillation. Am J Med. 2013;126:289–96.CrossRefPubMed Deedwania PC. New oral anticoagulants in elderly patients with atrial fibrillation. Am J Med. 2013;126:289–96.CrossRefPubMed
18.
Zurück zum Zitat Jacobs JM, Stessman J. New anticoagulant drugs among elderly patients is caution necessary?: Comment on «The use of dabigatran in elderly patients». Arch Intern Med. 2011;171:1287–8.CrossRefPubMed Jacobs JM, Stessman J. New anticoagulant drugs among elderly patients is caution necessary?: Comment on «The use of dabigatran in elderly patients». Arch Intern Med. 2011;171:1287–8.CrossRefPubMed
19.
Zurück zum Zitat Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47:285–95.CrossRefPubMed Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47:285–95.CrossRefPubMed
20.
Zurück zum Zitat Stangier J, Rathgen K, Stahle H, Mazur D. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet. 2010;49:259–68.CrossRefPubMed Stangier J, Rathgen K, Stahle H, Mazur D. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet. 2010;49:259–68.CrossRefPubMed
21.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
22.
Zurück zum Zitat Folstein MF, Folstein SE, McHugh PR. «Mini-mental state». A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–98.CrossRefPubMed Folstein MF, Folstein SE, McHugh PR. «Mini-mental state». A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–98.CrossRefPubMed
23.
Zurück zum Zitat Rule AD, Larson TS, Bergstralh EJ, Slezak JM, Jacobsen SJ, Cosio FG. Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease. Ann Intern Med. 2004;141:929–37.CrossRefPubMed Rule AD, Larson TS, Bergstralh EJ, Slezak JM, Jacobsen SJ, Cosio FG. Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease. Ann Intern Med. 2004;141:929–37.CrossRefPubMed
24.
Zurück zum Zitat Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31–41.CrossRefPubMed Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31–41.CrossRefPubMed
25.
Zurück zum Zitat Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47:1245–51.CrossRefPubMed Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47:1245–51.CrossRefPubMed
26.
Zurück zum Zitat Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJGM. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010;137:263–72.CrossRefPubMed Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJGM. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010;137:263–72.CrossRefPubMed
27.
Zurück zum Zitat Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJGM, Lip GYH. A novel userfriendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138:1093–100.CrossRefPubMed Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJGM, Lip GYH. A novel userfriendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138:1093–100.CrossRefPubMed
28.
Zurück zum Zitat Antovic JP, Skeppholm M, Eintrei J et al. Evaluation of coagulation assays versus LC-MS/MS for determinations of dabigatran concentrations in plasma. Eur J Clin Pharmacol. 2013;69:1875–81.CrossRefPubMed Antovic JP, Skeppholm M, Eintrei J et al. Evaluation of coagulation assays versus LC-MS/MS for determinations of dabigatran concentrations in plasma. Eur J Clin Pharmacol. 2013;69:1875–81.CrossRefPubMed
29.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
30.
Zurück zum Zitat Patel MR, Mahaffey KW, Garg J et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.CrossRefPubMed Patel MR, Mahaffey KW, Garg J et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.CrossRefPubMed
31.
Zurück zum Zitat European Medicines Agency. Pradaxa Summary of Product Characteristics. European Medicines Agency. 2013. European Medicines Agency. Pradaxa Summary of Product Characteristics. European Medicines Agency. 2013.
32.
Zurück zum Zitat Testa S, Tripodi A, Legnani C et al. Plasma levels of direct oral anticoagulants in real life patients with atrial fibrillation: Results observed in four anticoagulation clinics. Thromb Res. 2016;137:178–83.CrossRefPubMed Testa S, Tripodi A, Legnani C et al. Plasma levels of direct oral anticoagulants in real life patients with atrial fibrillation: Results observed in four anticoagulation clinics. Thromb Res. 2016;137:178–83.CrossRefPubMed
33.
Zurück zum Zitat Chan NC, Coppens M, Hirsh J et al. Real-world variability in dabigatran levels in patients with atrial fibrillation. J Thromb Haemost. 2015;13:353–9.CrossRefPubMed Chan NC, Coppens M, Hirsh J et al. Real-world variability in dabigatran levels in patients with atrial fibrillation. J Thromb Haemost. 2015;13:353–9.CrossRefPubMed
34.
Zurück zum Zitat Levey AS, Eckardt K, Tsukamoto Y et al. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2005;67:2089–100.CrossRefPubMed Levey AS, Eckardt K, Tsukamoto Y et al. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2005;67:2089–100.CrossRefPubMed
35.
Zurück zum Zitat FDA. Summary Review for Pradaxa. 2010. FDA. Summary Review for Pradaxa. 2010.
36.
Zurück zum Zitat Douxfils J, Mullier F, Dogne J. Dose tailoring of dabigatran etexilate: obvious or excessive? Expert Opin Drug Saf. 2015;14:1283–9.CrossRefPubMed Douxfils J, Mullier F, Dogne J. Dose tailoring of dabigatran etexilate: obvious or excessive? Expert Opin Drug Saf. 2015;14:1283–9.CrossRefPubMed
37.
Zurück zum Zitat Stangier J, Feuring M. Using the HEMOCLOT direct thrombin inhibitor assay to determine plasma concentrations of dabigatran. Blood Coagul Fibrinolysis. 2012;23:138–43.CrossRefPubMed Stangier J, Feuring M. Using the HEMOCLOT direct thrombin inhibitor assay to determine plasma concentrations of dabigatran. Blood Coagul Fibrinolysis. 2012;23:138–43.CrossRefPubMed
38.
Zurück zum Zitat Hawes EM, Deal AM, Funk-Adcock D et al. Performance of coagulation tests in patients on therapeutic doses of dabigatran: a cross-sectional pharmacodynamic study based on peak and trough plasma levels. J Thromb Haemost. 2013;11:1493–502.CrossRefPubMed Hawes EM, Deal AM, Funk-Adcock D et al. Performance of coagulation tests in patients on therapeutic doses of dabigatran: a cross-sectional pharmacodynamic study based on peak and trough plasma levels. J Thromb Haemost. 2013;11:1493–502.CrossRefPubMed
39.
Zurück zum Zitat Curvers J, van de Kerkhof D, Stroobants AK, van den Dool E, Scharnhorst V. Measuring direct thrombin inhibitors with routine and dedicated coagulation assays: which assay is helpful? Am J Clin Pathol. 2012;138:551–8.CrossRefPubMed Curvers J, van de Kerkhof D, Stroobants AK, van den Dool E, Scharnhorst V. Measuring direct thrombin inhibitors with routine and dedicated coagulation assays: which assay is helpful? Am J Clin Pathol. 2012;138:551–8.CrossRefPubMed
Metadaten
Titel
Real-Life Peak and Trough Dabigatran Plasma Measurements Over Time in Hospitalized Geriatric Patients with Atrial Fibrillation
verfasst von
E. Chaussade
Olivier Hanon
C. Boully
F. Labourée
L. Caillard
G. Gerotziafas
J.-S. Vidal
I. Elalamy
Publikationsdatum
14.10.2017
Verlag
Springer Paris
Erschienen in
The journal of nutrition, health & aging / Ausgabe 1/2018
Print ISSN: 1279-7707
Elektronische ISSN: 1760-4788
DOI
https://doi.org/10.1007/s12603-017-0982-4

Weitere Artikel der Ausgabe 1/2018

The journal of nutrition, health & aging 1/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.