Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Medicine
Published in: BMC Medicine 1/2015

Open Access 01-12-2015 | Research article

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

Authors: 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

Published in: BMC Medicine | Issue 1/2015

Login to get access

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% (inte rquartile 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.
Appendix
Available only for authorised users
Literature
1.
Hart RG, Benavente O, McBride R, Pearce LA. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med. 1999;131:492–501.CrossRefPubMed
2.
Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:160–98. doi:10.1378/chest.08-0670.CrossRef
3.
Wilke T, Groth A, Mueller S, Pfannkuche M, Verheyen F, Linder R, et al. Incidence and prevalence of atrial fibrillation: an analysis based on 8.3 million patients. Europace. 2013;15:486–93.CrossRefPubMed
4.
Ericson L, Bergfeldt L, Björholt I. Atrial fibrillation: the cost of illness in Sweden. Eur J Health Econ. 2011;12:479–87.CrossRefPubMed
5.
Hylek EM, Go AS, Chang Y, Jensvold NG, Henault LE, Selby JV, et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med. 2003;349:1019–26.CrossRefPubMed
6.
Connolly SJ, Pogue J, Eikelboom J, Flaker G, Commerford P, Franzosi MG, 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;118:2029–37.CrossRefPubMed
7.
Rosendaal FR, Cannegieter SC, van der Meer FJ, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost. 1993;69:236–9.PubMed
8.
Wan Y, Heneghan C, Perera R, Roberts N, Hollowell J, Glasziou P, et al. Anticoagulation control and prediction of adverse events in patients with atrial fibrillation: a systematic review. Circ Cardiovasc Qual Outcomes. 2008;1:84–91.CrossRefPubMed
9.
van Walraven C, Jennings A, Oake N, Fergusson D, Forster AJ. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest. 2006;129:1155–66.CrossRefPubMed
10.
Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.CrossRefPubMed
11.
Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.CrossRefPubMed
12.
Samsa GP, Matchar DB, Goldstein LB, Bonito AJ, Lux LJ, Witter DM, et al. Quality of anticoagulation management among patients with atrial fibrillation: results of a review of medical records from 2 communities. Arch Intern Med. 2000;160:967–73.CrossRefPubMed
13.
Kalra L, Yu G, Perez I, Lakhani A, Donaldson N. Prospective cohort study to determine if trial efficacy of anticoagulation for stroke prevention in atrial fibrillation translates into clinical effectiveness. BMJ. 2000;320:1236–9.CrossRefPubMedPubMedCentral
14.
Wieloch M, Själander A, Frykman V, Rosenqvist M, Eriksson N, Svensson PJ. Anticoagulation control in Sweden: reports of time in therapeutic range, major bleeding, and thrombo-embolic complications from the national quality registry AuriculA. Eur Heart J. 2011;32:2282–9.CrossRefPubMed
15.
Sullivan PW, Arant TW, Ellis SL, Ulrich H. The cost effectiveness of anticoagulation management services for patients with atrial fibrillation and at high risk of stroke in the US. Pharmacoeconomics. 2006;24:1021–33.CrossRefPubMed
16.
Beinema M, Brouwers JRBJ, Schalekamp T, Wilffert B. Pharmacogenetic differences between warfarin, acenocoumarol and phenprocoumon. Thromb Haemost. 2008;100:1052–7.PubMed
17.
Gadisseur AP, van der Meer FJ, Adriaansen HJ, Fihn SD, Rosendaal FR. Therapeutic quality control of oral anticoagulant therapy comparing the short-acting acenocoumarol and the long-acting phenprocoumon. Br J Haematol. 2002;117:940–6.CrossRefPubMed
18.
Baker WL, Cios DA, Sander SD, Coleman CI. Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States. J Manag Care Pharm. 2009;15:244–52.PubMed
19.
Behr S, Andersohn F, Garbe E. Risk of intracerebral hemorrhage associated with phenprocoumon exposure: a nested case-control study in a large population-based German database. Pharmacoepidemiol Drug Saf. 2010;19:722–30.CrossRefPubMed
20.
De Caterina R, Husted S, Wallentin L, Andreotti F, Arnesen H, Bachmann F, et al. General mechanisms of coagulation and targets of anticoagulants (Section I). Position paper of the ESC Working Group on Thrombosis–Task Force on Anticoagulants in Heart Disease. Thromb Haemost. 2013;109:569–79.CrossRefPubMed
21.
Reilly PA, Lehr T, Haertter S, Connolly SJ, Yusuf S, Eikelboom JW, et al. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol. 2014;63:321–8.CrossRefPubMed
22.
23.
Prochaska JH, Coldewey M, Gobel S, Keller K, Hendelmeier M, Konstantinides S, et al.; for the thrombEVAL Study Group. Evaluation of oral anticoagulation therapy: rationale and design of the thrombEVAL study programme. Eur J Prev Cardiol. 2014. [Epub ahead of print].
24.
Ansari AR, Bradley RA. Rank-sum tests for dispersions. Ann Math Stat. 1960;31:1174–89.CrossRef
25.
Gadisseur AP, Breukink-Engbers WG, van der Meer FJ, van den Besselaar AM, Sturk A, Rosendaal FR. 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;163:2639–46.CrossRefPubMed
26.
ROCKET-AF Study Investigators. Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation: rationale and design of the ROCKET AF study. Am Heart J. 2010;159:340–7.CrossRef
27.
Granger CB, Alexander JH, McMurray JJV, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92.CrossRefPubMed
28.
EINSTEIN-PE Investigators, Buller HR, Prins MH, Lensin AWA, Decousus H, Jacobson BF, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366:1287–97.CrossRef
29.
Fihn SD, Gadisseur AAP, Pasterkamp E, van der Meer FJM, Breukink-Engbers WGM, Geven-Boere LM, et al. Comparison of control and stability of oral anticoagulant therapy using acenocoumarol versus phenprocoumon. Thromb Haemost. 2003;90:260–6.PubMed
30.
Li T, Lange LA, Li X, Susswein L, Bryant B, Malone R, et al. Polymorphisms in the VKORC1 gene are strongly associated with warfarin dosage requirements in patients receiving anticoagulation. J Med Genet. 2006;43:740–4.CrossRefPubMedPubMedCentral
31.
Mushiroda T, Ohnishi Y, Saito S, Takahashi A, Kikuchi Y, Saito S, et al. Association of VKORC1 and CYP2C9 polymorphisms with warfarin dose requirements in Japanese patients. J Hum Genet. 2006;51:249–53.CrossRefPubMed
32.
Witt DM, Delate T, Clark NP, Martell C, Tran T, Crowther MA, et al. Outcomes and predictors of very stable INR control during chronic anticoagulation therapy. Blood. 2009;114:952–6.CrossRefPubMed
33.
Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369:1206–14.CrossRefPubMed
34.
Cromheecke ME, Levi M, Colly LP, de Mol BJ, Prins MH, Hutten BA, et al. Oral anticoagulation self-management and management by a specialist anticoagulation clinic: a randomised cross-over comparison. Lancet. 2000;356:97–102.CrossRefPubMed
35.
van den Besselaar AM, van der Meer FJ, Gerrits-Drabbe CW. Therapeutic control of oral anticoagulant treatment in the Netherlands. Am J Clin Pathol. 1988;90:685–90.CrossRefPubMed
36.
Reynolds MW, Fahrbach K, Hauch O, Wygant G, Estok R, Cella C, et al. Warfarin anticoagulation and outcomes in patients with atrial fibrillation: a systematic review and metaanalysis. Chest. 2004;126:1938–45.CrossRefPubMed
37.
Cannegieter SCS, Rosendaal FRF, Wintzen ARA, van der Meer FJF, Vandenbroucke JPJ, Briët EE. Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med. 1995;333:11–7.CrossRefPubMed
38.
Samsa GP, Matchar DB. Relationship between test frequency and outcomes of anticoagulation: a literature review and commentary with implications for the design of randomized trials of patient self-management. J Thromb Thrombolysis. 2000;9:283–92.CrossRefPubMed
39.
van Walraven C, Oake N, Coyle D, Taljaard M, Forster AJ. Changes in surrogate outcomes can be translated into clinical outcomes using a Monte Carlo model. J Clin Epidemiol. 2009;62:1306–15.CrossRefPubMed
40.
Wallentin L, Yusuf S, Ezekowitz MD, Alings M, Flather M, Franzosi MG, 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;376:975–83.CrossRefPubMed
41.
Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med. 1994;120:897–902.CrossRefPubMed
42.
Rose AJ, Miller DR, Ozonoff A, Berlowitz DR, Ash AS, Zhao S, et al. Gaps in monitoring during oral anticoagulation: insights into care transitions, monitoring barriers, and medication nonadherence. Chest. 2012;143:751–7.CrossRef
43.
Wilke T, Groth A, Mueller S, Pfannkuche M, Verheyen F, Linder R, 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;107:1053–65.CrossRefPubMed
44.
Go AS, Hylek EM, Borowsky LH, Phillips KA, Selby JV, Singer DE. Warfarin use among ambulatory patients with nonvalvular atrial fibrillation: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study. Ann Intern Med. 1999;131:927–34.CrossRefPubMed
45.
Hirsh J, Fuster V, Ansell J, Halperin JL. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Circulation. 2003;107:1692–711.CrossRefPubMed
46.
Van Spall HGC, Wallentin L, Yusuf S, Eikelboom JW, Nieuwlaat R, Yang S, et al. Variation in warfarin dose adjustment practice is responsible for differences in the quality of anticoagulation control between centers and countries: an analysis of patients receiving warfarin in the randomized evaluation of long-term anticoagulation therapy (RE-LY) trial. Circulation. 2012;126:2309–16.CrossRefPubMed
47.
Kim Y-K, Nieuwlaat R, Connolly SJ, Schulman S, Meijer K, Raju N, et al. Effect of a simple two-step warfarin dosing algorithm on anticoagulant control as measured by time in therapeutic range: a pilot study. J Thromb Haemost. 2010;8:101–6.CrossRefPubMed
48.
Poller L, Keown M, Ibrahim S, Lowe G, Moia M, Turpie AG, et al. An international multicenter randomized study of computer-assisted oral anticoagulant dosage vs. medical staff dosage. J Thromb Haemost. 2008;6:935–43.CrossRefPubMed
49.
50.
51.
Metadata
Title
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
Authors
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
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2015
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-015-0268-9

Other articles of this Issue 1/2015

BMC Medicine 1/2015 Go to the issue

Commentary

E-cigarette use and relations to tobacco and alcohol use among adolescents

Research article

The predictive value of current haemoglobin levels for incident tuberculosis and/or mortality during long-term antiretroviral therapy in South Africa: a cohort study

Review

PCSK9 inhibition: the way forward in the treatment of dyslipidemia

Commentary

Statin effects on atherosclerotic plaques: regression or healing?

Research article

Comparison of registered and published outcomes in randomized controlled trials: a systematic review

Research article

Implementing supported self-management for asthma: a systematic review and suggested hierarchy of evidence of implementation studies