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      Is the time in therapeutic range on coumarins predicted by previous time in therapeutic range?

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          Abstract

          Background

          The benefit of vitamin K antagonists depends on the time within the therapeutic range (TTR). A patient’s previous TTR could be a factor in the decision to change the anticoagulation regimen. However, the predictive value of a previous TTR for a future TTR is not well established, nor is it clear which TTR should prompt action.

          Objectives

          To investigate the predictive performance of a TTR and identify a threshold below which no recovery of TTR should be expected.

          Patients/Methods

          From 18 031 patients who used acenocoumarol in a first‐line anticoagulation clinic, a TTR was calculated over multiple periods of 90, 180, and 365 days each. We assessed the correlation between baseline and later TTR and the separation between groups by quintile of baseline TTR. We describe the proportion of patients who obtain a TTR≥ 70% conditional on baseline TTR.

          Results

          The correlation between baseline and later TTR was 0.25 (95% confidence interval [CI], 0.24‐0.26), 0.27 (95% CI, 0.26‐0.28) and 0.34 (95% CI, 0.32‐0.35) for analyses over 90, 180, and 365 days. Corresponding c statistics for discrimination by baseline group were 0.60, 0.61, and 0.63. The probability to obtain a TTR ≥70% increased with baseline TTR: from 42% with a baseline TTR of 50%‐65% when TTR was 100% (TTR calculated over 180 days).

          Conclusions

          We conclude that a current TTR hardly predicts a future TTR. Physicians and patients should deliberate together which probabilities to accept, take measures to improve TTR, and consider potential alternatives.

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          Most cited references15

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          A simple generalisation of the area under the ROC curve for multiple class classification problems

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            Vitamin K antagonists in heart disease: current status and perspectives (Section III). Position paper of the ESC Working Group on Thrombosis--Task Force on Anticoagulants in Heart Disease.

            Oral anticoagulants are a mainstay of cardiovascular therapy, and for over 60 years vitamin K antagonists (VKAs) were the only available agents for long-term use. VKAs interfere with the cyclic inter-conversion of vitamin K and its 2,3 epoxide, thus inhibiting γ-carboxylation of glutamate residues at the amino-termini of vitamin K-dependent proteins, including the coagulation factors (F) II (prothrombin), VII, IX and X, as well as of the anticoagulant proteins C, S and Z. The overall effect of such interference is a dose-dependent anticoagulant effect, which has been therapeutically exploited in heart disease since the early 1950s. In this position paper, we review the mechanisms of action, pharmacological properties and side effects of VKAs, which are used in the management of cardiovascular diseases, including coronary heart disease (where their use is limited), stroke prevention in atrial fibrillation, heart valves and/or chronic heart failure. Using an evidence-based approach, we describe the results of completed clinical trials, highlight areas of uncertainty, and recommend therapeutic options for specific disorders. Although VKAs are being increasingly replaced in most patients with non-valvular atrial fibrillation by the new oral anticoagulants, which target either thrombin or FXa, the VKAs remain the agents of choice for patients with atrial fibrillation in the setting of rheumatic valvular disease and for those with mechanical heart valves.
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              Patient characteristics associated with oral anticoagulation control: results of the Veterans AffaiRs Study to Improve Anticoagulation (VARIA).

              In patients receiving oral anticoagulation, improved control can reduce adverse outcomes such as stroke and major hemorrhage. However, little is known about patient-level predictors of anticoagulation control. To identify patient-level predictors of oral anticoagulation control in the outpatient setting. We studied 124,619 patients who received oral anticoagulation from the Veterans Health Administration from October 2006 to September 2008. The outcome was anticoagulation control, summarized using percentage of time in therapeutic International Normalized Ratio range (TTR). Data were divided into inception (first 6 months of therapy; 39,447 patients) and experienced (any time thereafter; 104,505 patients). Patient-level predictors of TTR were examined by multivariable regression. Mean TTRs were 48% for inception management and 61% for experienced management. During inception, important predictors of TTR included hospitalizations (the expected TTR was 7.3% lower for those with two or more hospitalizations than for the non-hospitalized), receipt of more medications (16 or more medications predicted a 4.3% lower than for patients with 0-7 medications), alcohol abuse (-4.6%), cancer (-3.1%), and bipolar disorder (-2.9%). During the experienced period, important predictors of TTR included hospitalizations (four or more hospitalizations predicted 9.4% lower TTR), more medications (16 or more medications predicted 5.1% lower TTR), alcohol abuse (-5.4%), female sex (- 2.9%), cancer (-2.7%), dementia (-2.6%), non-alcohol substance abuse (-2.4%), and chronic liver disease (-2.3%). Some patients receiving oral anticoagulation therapy are more challenging to maintain within the therapeutic range than others. Our findings can be used to identify patients who require closer attention or innovative management strategies to maximize benefit and minimize harm from oral anticoagulation therapy. © 2010 International Society on Thrombosis and Haemostasis.
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                Author and article information

                Contributors
                j.h.a.van.miert@umcg.nl , @JasperVanMiert
                Journal
                Res Pract Thromb Haemost
                Res Pract Thromb Haemost
                10.1002/(ISSN)2475-0379
                RTH2
                Research and Practice in Thrombosis and Haemostasis
                John Wiley and Sons Inc. (Hoboken )
                2475-0379
                30 March 2020
                May 2020
                : 4
                : 4 ( doiID: 10.1002/rth2.v4.4 )
                : 604-609
                Affiliations
                [ 1 ] Department of Hematology University of Groningen University Medical Center Groningen Groningen The Netherlands
                [ 2 ] Certe Thrombosis Service Groningen Groningen The Netherlands
                [ 3 ] Department of Epidemiology University of Groningen University Medical Center Groningen Groningen The Netherlands
                Author notes
                [*] [* ] Correspondence

                Jasper H. A. van Miert, Department of Hematology, University Medical Center Groningen, Huispostcode: AA24, Postbus 30.001, 9700 RB, Groningen The Netherlands.

                Email: j.h.a.van.miert@ 123456umcg.nl

                Author information
                https://orcid.org/0000-0002-5177-1660
                https://orcid.org/0000-0002-1492-7937
                https://orcid.org/0000-0001-9447-0465
                Article
                RTH212328
                10.1002/rth2.12328
                7292664
                32548559
                cff3ab20-18fd-46a4-a9d2-2f5cf3c1eddf
                © 2020 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals, Inc on behalf of International Society on Thrombosis and Haemostasis.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 07 November 2019
                : 01 February 2020
                : 25 February 2020
                Page count
                Figures: 3, Tables: 1, Pages: 6, Words: 4004
                Categories
                Original Article
                Original Article: Thrombosis
                Custom metadata
                2.0
                May 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.4 mode:remove_FC converted:12.06.2020

                acenocoumarol,anticoagulants,coumarins,decision support techniques,quality control

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