CC BY 4.0 · TH Open 2021; 05(01): e35-e42
DOI: 10.1055/s-0040-1722706
Original Article

Anticoagulation Prescription and Outcomes in Relation to Renal Function in Patients with Atrial Fibrillation: Results from GLORIA-AF

Sake J. van der Wall
1   Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
,
Christine Teutsch
2   Department of CardioMetabolism and Respiratory Medicine, Boehringer Ingelheim International GmbH, Ingelheim, Germany
,
Sergio J. Dubner
3   Electrophysiology Service, Clínica y Maternidad Suizo Argentina, Buenos Aires, Argentina
,
Hans-Christoph Diener
4   Faculty of Medicine, University of Duisburg-Essen, Germany
,
Jonathan L. Halperin
5   The Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, United States
,
Chang Sheng Ma
6   Cardiology Department, Atrial Fibrillation Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
,
Kenneth J. Rothman
7   RTI Health Solutions, Research Triangle Institute, Research Triangle Park, North Carolina, United States
,
Miney Paquette
8   Department of Medicine, Boehringer Ingelheim, Burlington, Ontario, Canada; Global Epidemiology at Boehringer Ingelheim GmbH, Ingelheim, Germany
,
Kristina Zint
9   Global Epidemiology Department, Boehringer Ingelheim International GmbH, Ingelheim, Germany
,
Lionel Riou França
9   Global Epidemiology Department, Boehringer Ingelheim International GmbH, Ingelheim, Germany
,
Shihai Lu
10   Biostatistics and Data Sciences Department, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, United States
,
11   Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom
12   Department of Clinical Medicine, Aalborg Thrombosis Research Unit, Aalborg University, Aalborg, Denmark
,
Menno V. Huisman*
1   Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
,
on behalf of the GLORIA-AF Investigators
› Institutsangaben
Funding This study was funded by Boehringer Ingelheim GmbH.

Abstract

Objective Anticoagulation management in patients with atrial fibrillation (AF) and impaired renal function is challenging. This study aimed to evaluate anticoagulation prescription patterns in relation to renal function and to describe 2-year clinical outcomes among dabigatran users.

Methods Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) is an international, prospective, and observational study program involving patients with newly diagnosed AF at risk for stroke. Prescription patterns were assessed by creatinine clearance (CrCl) at enrollment. Dabigatran users were followed for 2 years. Clinical outcomes were standardized for stroke and bleeding risk, based on CHA2DS2-VASc and HAS-BLED scores, with missing values imputed.

Results Baseline CrCl values were available for 12,056 of 15,308 eligible patients (79%). With declining renal function, prescriptions increased for vitamin K antagonists (VKAs) and decreased for dabigatran (30–47% and 34–12%, respectively). The prescription of other non-vitamin K antagonists remained similar across CrCl groups (14–19%). In 4,873 dabigatran users, standardized stroke rates were low across all CrCl groups; 0.58/100 patient-years (95% confidence interval [CI]: 0.30–0.90) in CrCl ≥80 mL/min, 0.85 (95% CI: 0.48–1.21) in CrCl 50 to 79 mL/min, and 0.33 (95% CI: 0.06–1.11) in CrCl 30 to 49 mL/min. Similarly, major bleeding rates were low and numerically increased with declining renal function (0.68/100 patient-years, 95% CI: 0.39–1.03; 0.92, 95% CI: 0.58–1.32; and 1.26, 95% CI: 0.66–1.97, respectively).

Conclusion In patients with AF, VKA prescriptions increased and dabigatran prescriptions decreased with declining renal function. Rates of stroke and major bleeding in dabigatran patients remained low across the categories of renal impairment.

Note

This study is registered with ClinicalTrials.gov with identifier no. NCT01468701 (http://www.clinicaltrials.gov).


* Joint senior authors and co-Chairs of the GLORIA-AF Registry Program.


# For complete list of Phase II GLORIA AF Principal Investigators, please refer to the [Supplementary Material].


Supplementary Material



Publikationsverlauf

Eingereicht: 02. September 2020

Angenommen: 03. Dezember 2020

Artikel online veröffentlicht:
06. Februar 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Bonde AN, Lip GY, Kamper AL. et al. Net clinical benefit of antithrombotic therapy in patients with atrial fibrillation and chronic kidney disease: a nationwide observational cohort study. J Am Coll Cardiol 2014; 64 (23) 2471-2482
  • 2 Kooiman J, van de Peppel WR, van der Meer FJ, Huisman MV. Incidence of chronic kidney disease in patients with atrial fibrillation and its relevance for prescribing new oral antithrombotic drugs. J Thromb Haemost 2011; 9 (08) 1652-1653
  • 3 Olesen JB, Lip GY, Kamper AL. et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med 2012; 367 (07) 625-635
  • 4 Birman-Deych E, Radford MJ, Nilasena DS, Gage BF. Use and effectiveness of warfarin in Medicare beneficiaries with atrial fibrillation. Stroke 2006; 37 (04) 1070-1074
  • 5 Larock AS, Mullier F, Sennesael AL. et al. Appropriateness of prescribing dabigatran etexilate and rivaroxaban in patients with nonvalvular atrial fibrillation: a prospective study. Ann Pharmacother 2014; 48 (10) 1258-1268
  • 6 Wilke T, Groth A, Mueller S. et al. Oral anticoagulation use by patients with atrial fibrillation in Germany. Adherence to guidelines, causes of anticoagulation under-use and its clinical outcomes, based on claims-data of 183,448 patients. Thromb Haemost 2012; 107 (06) 1053-1065
  • 7 January CT, Wann LS, Calkins H. et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: a Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation 2019; 140 (02) e125-e151
  • 8 Steffel J, Verhamme P, Potpara TS. et al; ESC Scientific Document Group. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 2018; 39 (16) 1330-1393
  • 9 Food and Drug Administration (FDA). 2015 Prescribing Information, Pradaxa. Accessed June 2020 at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s028lbl.pdf
  • 10 Food and Drug Administration (FDA). 2012 Prescribing Information, Eliquis. Accessed June 2020 at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202155s000lbl.pdf
  • 11 Food and Drug Administration (FDA). 2020 Prescribing Information, Xarelto. Accessed June 2020 at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202155s000lbl.pdf
  • 12 Raccah BH, Perlman A, Danenberg HD, Pollak A, Muszkat M, Matok I. Major bleeding and hemorrhagic stroke with direct oral anticoagulants in patients with renal failure: systematic review and meta-analysis of randomized trials. Chest 2016; 149 (06) 1516-1524
  • 13 Huisman MV, Lip GY, Diener HC. et al. Design and rationale of Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation: a global registry program on long-term oral antithrombotic treatment in patients with atrial fibrillation. Am Heart J 2014; 167 (03) 329-334
  • 14 Huisman MV, Rothman KJ, Paquette M. et al; GLORIA-AF Investigators. Antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation: the GLORIA-AF Registry, Phase II. Am J Med 2015; 128 (12) 1306-13.e1
  • 15 Mazurek M, Teutsch C, Diener HC. et al; GLORIA-AF Investigators. Safety and effectiveness of dabigatran at 2 years: final outcomes from phase II of the GLORIA-AF registry program. Am Heart J 2019; 218: 123-127
  • 16 January CT, Wann LS, Alpert JS. et al; ACC/AHA Task Force Members. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130 (23) 2071-2104
  • 17 Kirchhof P, Benussi S, Kotecha D. et al; ESC Scientific Document Group. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37 (38) 2893-2962
  • 18 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
  • 19 White IR, Royston P, Wood AM. Multiple imputation using chained equations: Issues and guidance for practice. Stat Med 2011; 30 (04) 377-399
  • 20 Schomaker M, Heumann C. Bootstrap inference when using multiple imputation. Stat Med 2018; 37 (14) 2252-2266
  • 21 Boriani G, Laroche C, Diemberger I. et al. Glomerular filtration rate in patients with atrial fibrillation and 1-year outcomes. Sci Rep 2016; 6: 30271
  • 22 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 (21) 2363-2372
  • 23 Hijazi Z, Hohnloser SH, Oldgren J. et al. Efficacy and safety of dabigatran compared with warfarin in relation to baseline renal function in patients with atrial fibrillation: a RE-LY (randomized evaluation of long-term anticoagulation therapy) trial analysis. Circulation 2014; 129 (09) 961-970
  • 24 Ramagopalan SV, Stamp E, Sammon CJ. et al. Renal function and oral anticoagulant treatment of incident non-valvular atrial fibrillation: a retrospective study. Future Cardiol 2019; 15 (04) 301-309
  • 25 Steinberg BA, Holmes DN, Piccini JP. et al; Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Investigators and Patients. Early adoption of dabigatran and its dosing in US patients with atrial fibrillation: results from the outcomes registry for better informed treatment of atrial fibrillation. J Am Heart Assoc 2013; 2 (06) e000535
  • 26 Connolly SJ, Ezekowitz MD, Yusuf S. et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361 (12) 1139-1151