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DOI: 10.1160/TH16-03-0184
Control of anticoagulation with vitamin K antagonists: overestimation of median time in therapeutic range when assessed by linear interpolation
Publication History
Received:
04 April 2016
Accepted after major revision:
07 June 2016
Publication Date:
02 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/201604/lookinside/thumbnails/10-1160-th16-03-0184-1.jpg)
Summary
Patients receiving vitamin K–antagonists are monitored by regular assessment of the International Normalized Ratio (INR). There are two popular methods for therapeutic control of anticoagulation in patient groups: 1) Time in Therapeutic Range (TTR) assessed by linear interpolation of successive INR measurements; 2) the cross-sectional proportion (CSP) of all patients’ last INRs within range. The purpose of the present study is to compare the two methods using data from 53 Dutch Thrombosis Centres and to develop a semi-quantitative model for TTR based on different types of INR change. Different groups of around 400,000 patients in four consecutive years were evaluated: patients in the induction phase, short-term, long-term, low-target range, high-target range, receiving either acenocoumarol or phenprocoumon, and performing self-management. Each Centre provided TTR and CSP results for each patient group. TTR and CSP were compared using the Wilcoxon signed-rank test. Separately, we analysed the relationship between consecutive INR results regarding in or out of range and their frequency of occurrence in patients of two different cohorts. Good correlation was observed between TTR and CSP (correlation coefficient 0.694–0.950 in low-target range). In long-term acenocoumarol patients (low-target range) the median TTR was significantly higher than CSP (80.0 % and 78.7 %, respectively; p<0.001). In long-term phenprocoumon patients (low-target range) there was no significant difference between median TTR (83.0 %) and median CSP (82.6 %). In conclusion, the correlation between TTR assessed by linear interpolation and CSP was good. TTR assessed by linear interpolation was higher than CSP in patients on acenocoumarol.
# The first two authors contributed equally to this work.
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References
- 1 Connolly SJ, Pogue J, Eikelboom J. et al. Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation 2008; 118: 2029-2037.
- 2 Poli D, Antonucci E, Testa S. et al. Bleeding risk in very old patients on vitamin K antagonist treatment. Results of a prospective collaborative study on elderly patients followed by Italian centres for anticoagulation. Circulation 2011; 124: 824-829.
- 3 Van den Besselaar AM. Recommended method for reporting therapeutic control of oral anticoagulant therapy. Control of Anticoagulation Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 1990; 63: 316-317.
- 4 Rosendaal FR, Cannegieter SC, van der Meer FJ, Briët E.. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993; 69: 236-239.
- 5 Azar AJ, Deckers JW, Rosendaal FR. et al. Assessment of therapeutic quality control in a long-term anticoagulant trial in post-myocardial infarction patients. Thromb Haemost 1994; 72: 347-351.
- 6 Bezemer ID, Roemer WH, Penning-van Beest FJ. et al. INR control calculation: comparison of Dutch and international methods. Neth J Med 2013; 71: 194-198.
- 7 Schmitt L, Speckman J, Ansell J.. Quality assessment of anticoagulation dose management: comparative evaluation of measures of time-in-therapeutic range. J Thromb Thrombolysis 2003; 15: 213-216.
- 8 Chan P, Li W, Hai J. et al. Time in therapeutic range and percentage of international normalized ratio in the therapeutic range as a measure of quality of anticoagulation control in patients with atrial fibrillation. Can J Cardiol. 2015 Epub ahead of print.
- 9 Caldeira D, Cruz I, Morgado G. et al. Is the time in therapeutic range using the ratio of tests equivalent to the Rosendaal method?. Blood Coagul Fibrinolysis 2015; 26: 972-976.
- 10 Abumuaileq RR, Abu-Assi E, Raposeiras-Roubin S. et al. Evaluation of SAMe-TT2R2 risk score for predicting the quality of anticoagulation control in a real-world cohort of patients with non-valvular atrial fibrillation on vitamin-K antagonists. Europace 2015; 17: 711-717.
- 11 Hutten BA, Prins MH, Redekop WK. et al. Comparison of three methods to assess therapeutic quality control of treatment with vitamin K antagonists. Thromb Haemost 1999; 82: 1260-1263.
- 12 Singer DE, Hellkamp AS, Yuan Z. et al. Alternative calculations of individual patient time in therapeutic range while taking warfarin: results from the ROCKET AF trial. J Am Heart Assoc 2015; 04: e001349.
- 13 White HD, Gruber M, Feyzi J. et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Intern Med 2007; 167: 239-245.
- 14 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: 975-983.
- 15 De Caterina R, Husted S, Wallentin L. et al New oral anticoagulants in atrial fibrillation and acute coronary syndromes. ESC Working Group on Thrombosis – Task Force on Anticoagulants in Heart Disease Position Paper. J Am Coll Cardiol 2012; 59: 1413-1425.
- 16 Camm AJ, Lip GY, De Caterina R. et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation – Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012; 33: 2719-2747.
- 17 Breukink-Engbers WG. Monitoring therapy with anticoagulants in The Netherlands. Sem Thromb Hemost 1999; 25: 37-42.
- 18 Van Geest-Daalderop JH, Sturk A, Levi M. et al Extent and quality of anti-coagulation treatment with coumarin derivatives by the Dutch Thrombosis Services. Ned Tijdschr Geneeskd 2004; 148: 730-735.
- 19 Netherlands Federation of Thrombosis Services. Summary medical annual reports. Available at http://www.fnt.nl/
- 20 Van Leeuwen Y, Rombouts EK, Kruithof CJ. et al Improved control of oral anticoagulant dosing: a randomized controlled trial comparing two computer algorithms. J Thromb Haemost 2007; 05: 1644-1649.
- 21 Biedermann JS, van Rein N, van den Besselaar AM. et al. Impact of point-of-care INR monitoring on quality of treatment with vitamin K antagonists in non-self-monitoring patients: a cohort study. J Thromb Haemost. 2016 Epub ahead of print.
- 22 Braun S, Spannagl M, Völler H.. Patient self-testing and self-management of oral anticoagulation. Anal Bioanal Chem 2009; 393: 1463-1471.
- 23 Fihn SD, Gadisseur A, Pasterkamp E. et al. Comparison of control and stability of oral anticoagulant therapy using acenocoumarol versus phenprocoumon. Thromb Haemost 2003; 90: 260-266.
- 24 Barcellona D, Vannini ML, Fenu L. et al. Warfarin or acenocoumarol: which is better in the management of oral anticoagulants?. Thromb Haemost 1998; 80: 899-902.
- 25 Ansell J, Hollowell J, Pengo V. et al. Descriptive analysis of the process and quality of oral anticoagulation management in real-life practice in patients with chronic non-valvular atrial fibrillation: the international study of anticoagulation management (ISAM). J Thromb Thrombolysis 2007; 23: 83-91.
- 26 Wan Y, Henegan C, Perera R. et al. Anticoagulation control and prediction of adverse events in patients with atrial fibrillation. A systematic review. Circ Cardiovasc Qual Outcomes 2008; 01: 84-91.
- 27 Fitzmaurice DA, Accetta G, Haas S. et al. Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists. Br J Haematol. 2016 Epub ahead of print.
- 28 Gadisseur AP, Breukink-Engbers WG, Van der Meer FJ. et al. Comparison of the quality of oral anticoagulant therapy through patient self-management and management by specialized anticoagulation clinics in the Netherlands: a randomized clinical trial. Arch Intern Med 2003; 163: 2639-2646.