The Clinical Impact of Different Coagulometers on Patient Outcomes
Long-term anticoagulation therapy using vitamin K antagonists (VKA) is used in millions of patients worldwide to reduce the risk of thrombotic or thromboembolic events. Control and monitoring of VKA therapy is improved by the regular self-measurement of international normalized ratio (INR) using a home monitoring device. This retrospective analysis of a large cohort of patients in the Netherlands seeks to determine whether the choice of INR monitor could have a clinical impact on patient outcomes.
The National Thrombosis Service provides medical supervision, training and support to anticoagulant patients eligible for home-monitoring of INR in the Netherlands. Two INR monitors (CoaguChek XS and INRatio2) have been distributed at random to patients since June 2011, and patient self-testing data (INR measurements and other clinical parameters) have been recorded to measure and improve treatment outcomes. The data have been retrospectively analyzed to determine any effect of the choice of monitor. Univariate and multivariate statistical tests are used to assess any differences between groups in terms of efficacy and safety parameters.
Data from 4,326 patients were collated, and 156,507 INR values were included in the analysis. Over half the patients (54.3%) were being treated for atrial fibrillation, and 77.6% were prescribed acenocoumarol. There were few differences between the patient populations using the two different monitors. Anticoagulant control overall was good, with high percentage of time (87.9%) in the appropriate INR range and low incidence of excessively high or low INR values (0.085/month). Minor clinical events related to safety were low (0.78 per patient-year) and showed few differences between monitors. Mortality rates were similar [hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.65–1.70].
Self-testing data from a large cohort of patients in the Netherlands suggest that there is no clinically relevant effect of the choice of coagulation monitor (CoaguChek XS or INRatio2) on the time in therapeutic range (TTR), minor or fatal outcomes of long-term anticoagulation management.
- European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery, Camm AJ, et al. Guidelines for the management of atrial fibrillation: the task force for the management of atrial fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31(19):2369–429. CrossRef
- Friberg L, Bergfeldt L. Atrial fibrillation prevalence revisited. J Intern Med. 2013;274(5):461–8. CrossRef
- 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. CrossRef
- Morgan CL, McEwan P, Tukiendorf A, Robinson PA, Clemens A, Plumb JM. Warfarin treatment in patients with atrial fibrillation: observing outcomes associated with varying levels of INR control. Thromb Res. 2009;124(1):37–41. CrossRef
- Torn M, Cannegieter SC, Bollen WL, van der Meer FJ, van der Wall EE, Rosendaal FR. Optimal level of oral anticoagulant therapy for the prevention of arterial thrombosis in patients with mechanical heart valve prostheses, atrial fibrillation, or myocardial infarction: a prospective study of 4202 patients. Arch Intern Med. 2009;169(13):1203–9. CrossRef
- Veeger NJ, Piersma-Wichers M, Tijssen JG, Hillege HL, van der Meer J. Individual time within target range in patients treated with vitamin K antagonists: main determinant of quality of anticoagulation and predictor of clinical outcome. A retrospective study of 2300 consecutive patients with venous thromboembolism. Br J Haematol. 2005;128(4):513–9. CrossRef
- Heneghan C, Ward A, Perera R, et al. Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data. Lancet. 2012;379(9813):322–34. CrossRef
- DeSantis G, Hogan-Schlientz J, Liska G, et al. STABLE results: warfarin home monitoring achieves excellent INR control. Am J Manag Care. 2014;20(3):202–9.
- Cumberworth A, Mabvuure NT, Hallam MJ, Hindocha S. Is home monitoring of international normalised ratio safer than clinic-based monitoring? Interact CardioVasc Thorac Surg. 2013;16(2):198–201. CrossRef
- Garcia-Alamino JM, Ward AM, Alonso-Coello P. Self-monitoring and self-management of oral anticoagulation. Cochrane Database Syst Rev. 2010;4:CD003839.
- Bloomfield HE, Krause A, Greer N, et al. Meta-analysis: effect of patient self-testing and self-management of long-term anticoagulation on major clinical outcomes. Ann Intern Med. 2011;154:472–82. CrossRef
- Heneghan C, Alonso-Coello P, Garcia-Alamino JM, Perera R, Meats E, Glasziou P. Self-monitoring of oral anticoagulation: a systematic review and meta-analysis. Lancet. 2006;367(9508):S404–11. CrossRef
- Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e152S–84S.
- Keeling D, Baglin T, Tait C, et al. Guidelines on oral anticoagulation with warfarin––fourth edition. Br J Haematol. 2011;154(3):311–24. CrossRef
- Jones M, McEwan P, Morgan CL, Peters JR, Goodfellow J, Currie CJ. Evaluation of the pattern of treatment, level of anticoagulation control, and outcome of treatment with warfarin in patients with non-valvar atrial fibrillation: a record linkage study in a large British population. Heart. 2005;91:472–7. CrossRef
- Gallagher AM, Setakis E, Plumb JM, Clemens A, van Staa TP. Risks of stroke and mortality associated with suboptimal anticoagulation in atrial fibrillation patients. Thromb Haemost. 2011;106(5):968–77. CrossRef
- Rose AJ, Hylek EM, Ozonoff A, Ash AS, Reisman JI, Berlowitz DR. Risk-adjusted percent time in therapeutic range as a quality indicator for outpatient oral anticoagulation: results of the Veterans Affairs study to improve anticoagulation (VARIA). Circ Cardiovasc Qual Outcomes. 2011;4(1):22–9. CrossRef
- Rose AJ, Hylek EM, Ozonoff A, Ash AS, Reisman JI, Berlowitz DR. Patient characteristics associated with oral anticoagulation control: results of the Veterans affairs study to improve anticoagulation (VARIA). J Thromb Haemost. 2010;8(10):2182–91. CrossRef
- Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008;133:160S–98S. CrossRef
- Lind M, Fahlen M, Kosiborod M, Eliasson B, Odén A. Variability of INR and its relationship with mortality, stroke, bleeding and hospitalisations in patients with atrial fibrillation. Thromb Res. 2012;129:32–5. CrossRef
- van Dolder BD, van Geest-Daalderop JJH, van’t Land RP, Levi MM, Piersma-Wichers G. De kunst van het doseren: Richtlijn, leidraad en informatie voor het doseren van vitamine K-antagonisten. Available from http://www.fnt.nl/. Accessed April 2014 (in Dutch).
- Bezemer ID, Roemer WH, Penning-van Beest FJ, van Eekelen E, Kramer MH. INR control calculation: comparison of Dutch and international methods. Neth J Med. 2013;71(4):194–8.
- Erkens PM, ten Cate H, Büller HR, Prins MH. Benchmark for time in therapeutic range in venous thromboembolism: a systematic review and meta-analysis. PLoS One. 2012;7(9):e42269. CrossRef
- Rosendaal R, Cannegieter S, van der Meer F, van der Meer F, Briet E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost. 1993;69(3):236–9.
- Prentice RL, Williams BJ, Peterson AV. On the regression analysis of multiple failure time data. Biometrika. 1981;68(2):373–9. CrossRef
- Lin DY, Wei LJ. The robust inference for the Cox proportional hazards model. J Am Stat Assoc. 1989;84:1074–8. CrossRef
- Wallentin L, Yusuf S, Ezekowitz MD, et al. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet. 2010;376(9745):975–83. CrossRef
- Gómez-Outes A, Terleira-Fernández AI, Calvo-Rojas G, Suárez-Gea ML, Vargas-Castrillón E. Dabigatran, rivaroxaban, or apixaban versus warfarin in patients with nonvalvular atrial fibrillation: a systematic review and meta-analysis of subgroups. Thrombosis. 2013;2013:640723. CrossRef
- Di Minno MN, Russolillo A, Di Minno A, Camera M, Parolari A, Tremoli E. Direct anticoagulant drugs to overcome limitations of vitamin K antagonists. A critical appraisal of data in atrial fibrillation patients. Expert Opin Emerg Drugs. 2013;18(1):9–23. CrossRef
- Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093–104. CrossRef
- 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 meta-analysis of randomised trials. Lancet. 2014;383(9921):955–62. CrossRef
- Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–51. CrossRef
- Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91. CrossRef
- Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92. CrossRef
- Rose AJ, Berlowitz DR, Ash AS, Ozonoff A, Hylek EM, Goldhaber-Fiebert JD. The business case for quality improvement: oral anticoagulation for atrial fibrillation. Circ Cardiovasc Qual Outcomes. 2011;4(4):416–24. CrossRef
- Christensen TD, Larsen TB. Precision and accuracy of point-of-care testing coagulometers used for self-testing and self-management of oral anticoagulation therapy. J Thromb Haemost. 2012;10:251–60. CrossRef
- Sharma P, Scotland G, Cruickshank M, et al. Clinical and cost-effectiveness of point-of-care tests (CoaguChek system, INRatio2 PT/INR monitor and ProTime microcoagulation system) for the self-monitoring of the coagulation status of people receiving long-term vitamin K antagonist therapy compared with standard UK practice: systematic review and economic evaluation. Aberdeen HTA Group, Institute of Applied Health Sciences, University of Aberdeen, 2013. Available from http://www.nice.org.uk/nicemedia/live/14091/66498/66498.pdf. Accessed May 2014.
- Azarnoush K, Camilleri L, Aublet-Cuvelier B, et al. Results of the first randomized French study evaluating self-testing of the international normalized ratio. J Heart Valve Dis. 2011;20(5):518–25.
- Hemkens LG, Hilden KM, Hartschen S, et al. A randomized trial comparing INR monitoring devices in patients with anticoagulation self-management: evaluation of a novel error-grid approach. J Thromb Thrombolysis. 2008;26:22–30. CrossRef
- Lam J, Schulman S, Witt DM, Vandvik PO, Qayyum F, Holbrook AM. Anticoagulation control with daily low-dose vitamin K to reduce clinically adverse outcomes and international normalized ratio variability: a systematic review and meta-analysis. Pharmacotherapy. 2013;33(11):1184–90. CrossRef
- The Clinical Impact of Different Coagulometers on Patient Outcomes
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Advances in Therapy
Volume 31, Issue 6 , pp 639-656
- Cover Date
- Print ISSN
- Online ISSN
- Springer Healthcare
- Additional Links
- CoaguChek XS
- International normalized ratio (INR)
- Patient self-monitoring (PSM)
- Patient self-testing (PST)
- Point of care (POC) test (POCT)
- Time in therapeutic range (TTR)
- Time in target range
- Vitamin K antagonist (VKA)
- Industry Sectors
- Author Affiliations
- 1. De Nationale Trombose Dienst (The National Thrombosis Service), Zonneoordlaan 17, 6718 TK, Ede, The Netherlands
- 2. Department of Cardiology, Pasana Care Group, Birdaarderstraatweg 70, 9101 DC, Dokkum, The Netherlands
- 3. LaboMed Coagulation Center, Tauentzienstrasse 7 b/c, 10789, Berlin, Germany