Quality of oral anticoagulation with phenprocoumon in regular medical care and its potential for improvement in a telemedicine-based coagulation service--results from the prospective, multi-center, observational cohort study thrombEVAL

Jürgen H Prochaska, Sebastian Göbel, Karsten Keller, Meike Coldewey, Alexander Ullmann, Heidrun Lamparter, Claus Jünger, Zaid Al-Bayati, Christina Baer, Ulrich Walter, Christoph Bickel, Hugo ten Cate, Thomas Münzel, Philipp S Wild, Jürgen H Prochaska, Sebastian Göbel, Karsten Keller, Meike Coldewey, Alexander Ullmann, Heidrun Lamparter, Claus Jünger, Zaid Al-Bayati, Christina Baer, Ulrich Walter, Christoph Bickel, Hugo ten Cate, Thomas Münzel, Philipp S Wild

Abstract

Background: The majority of studies on quality of oral anticoagulation (OAC) therapy with vitamin K-antagonists are performed with short-acting warfarin. Data on long-acting phenprocoumon, which is frequently used in Europe for OAC therapy and is considered to enable more stable therapy adjustment, are scarce. In this study, we aimed to assess quality of OAC therapy with phenprocoumon in regular medical care and to evaluate its potential for optimization in a telemedicine-based coagulation service.

Methods: In the prospective observational cohort study program thrombEVAL we investigated 2,011 patients from regular medical care in a multi-center cohort study and 760 patients from a telemedicine-based coagulation service in a single-center cohort study. Data were obtained from self-reported data, computer-assisted personal interviews, and laboratory measurements according to standard operating procedures with detailed quality control. Time in therapeutic range (TTR) was calculated by linear interpolation method to assess quality of OAC therapy. Study monitoring was carried out by an independent institution.

Results: Overall, 15,377 treatment years and 48,955 international normalized ratio (INR) measurements were analyzed. Quality of anticoagulation, as measured by median TTR, was 66.3% (interquartile range (IQR) 47.8/81.9) in regular medical care and 75.5% (IQR 64.2/84.4) in the coagulation service (P <0.001). Stable anticoagulation control within therapeutic range was achieved in 63.8% of patients in regular medical care with TTR at 72.1% (IQR 58.3/84.7) as compared to 96.4% of patients in the coagulation service with TTR at 76.2% [(IQR 65.6/84.7); P = 0.001)]. Prospective follow-up of coagulation service patients with pretreatment in regular medical care showed an improvement of the TTR from 66.2% (IQR 49.0/83.6) to 74.5% (IQR 62.9/84.2; P <0.0001) in the coagulation service. Treatment in the coagulation service contributed to an optimization of the profile of time outside therapeutic range, a 2.2-fold increase of stabile INR adjustment and a significant decrease in TTR variability by 36% (P <0.001).

Conclusions: Quality of anticoagulation with phenprocoumon was comparably high in this real-world sample of regular medical care. Treatment in a telemedicine-based coagulation service substantially improved quality of OAC therapy with regard to TTR level, frequency of stable anticoagulation control, and TTR variability.

Trial registration: ClinicalTrials.gov, unique identifier NCT01809015, March 8, 2013.

Figures

Figure 1
Figure 1
Quality of oral anticoagulation therapy in regular medical care and a telemedicine-based coagulation service.(A) Comparison of quality of oral anticoagulation therapy in in patients of regular medical care and coagulation service. (B) Comparison of quality of oral anticoagulation therapy in in patients of regular medical care and coagulation service in subsample of patients with stable anticoagulation control. (C) Intra-individual comparison of quality of oral anticoagulation in patients treated first in regular medical care (blue) and afterwards in coagulation service (red). (D) Intra-individual comparison of quality of oral anticoagulation in patients treated first in regular medical care (blue) and afterwards in coagulation service (red) in subsample of patients with stable anticoagulation control. Time in therapeutic range is calculated according to linear interpolation method and presented as median (first quartile/third quartile); P value for z-test. Mean TTR values are depicted graphically as asterisks within box-plots. TTR variability is expressed by median absolute deviation, P value for Ansari-Bradley test. Absolute and relative frequency of stable oral anticoagulation control is depicted.
Figure 2
Figure 2
Profile of time outside therapeutic range in regular medical care and coagulation service.(A) Relative frequency of time below therapeutic range. (B) Relative frequency of time above therapeutic range. Box-plots of profile of time outside therapeutic range of regular medical care and coagulation service. Time outside therapeutic range is presented as median (first quartile/third quartile); mean values are depicted graphically as asterisks within box-plots. Variability of frequency outside therapeutic range is expressed by median absolute deviation, P value for Ansari-Bradley test.
Figure 3
Figure 3
Development of time in therapeutic range over time in a specialized coagulation service in comparison to regular medical care. Time in therapeutic range (TTR) is assessed according to linear interpolation method. Median TTR values are depicted for both cohorts for each time point. Values of regular medical care are demonstrated in red, for coagulation service in blue.

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