© 2003 Schattauer GmbH, Stuttgart
260
Introduction
The indications for long-term therapy with coumarin anticoag-
ulants have broadened considerably over the past few decades.
Although this therapy has been made safer by improved labora-
tory testing and establishment of clear therapeutic ranges for
intensity, a significant risk of complications persists and the
management of patients taking anticoagulants remains subopti-
mal. In various studies of patients taking coumarin anticoagu-
lants, the international normalised ratio (INR), used to monitor
the intensity of anticoagulation, is outside the prescribed thera-
peutic range 10% to 70% of the time (1). This is undesirable
Comparison of control and stability of oral anticoagulant
therapy using acenocoumarol versus phenprocoumon
Stephan D. Fihn
1, 2
,Alain A. P. Gadisseur
4
, Edwin Pasterkamp
3
, Felix J. M. van der Meer
4
,
W. G. Mimi Breukink-Engbers
5
, Lya M. Geven-Boere
6
, Erik van Meegen
7
, Hanneke de Vries-
Goldschmeding
8
, Irma Antheunissen-Anneveld
9
,Annelies R. van’t Hoff
10
, Derk Harderman
11
,
Margriet Smink
12
, Frits R. Rosendaal
3, 4
1
Northwest Health Services Research Center of Excellence,Veteran Affairs Puget Sound Health Care System, the
2
Department
of Medicine of the University of Washington, Seattle,Washington, USA,
3
Department of Clinical Epidemiology and Hemostasis and
4
Thrombosis Center of the Leiden University Medical Center,
5
Oostgelderland Anticoagulation Clinic, Lichtenvoorde;
6
Leeuwarden
Anticoagulation Clinic;
7
Anticoagulation Clinic of the Hague;
8
Thrombosis Center of the Utrecht Division of the Dutch Red Cross,
9
Schiedam Anticoagulation Clinic,
10
Anticoagulation Clinic of Midden-Brabant,
11
Anticoagulation Clinic Zuid-West Friesland,
12
Anticoagulation Service Alkmaar,The Netherlands
Thromb Haemost 2003; 90: 260–6
phenprocoumon were within the therapeutic range 50% of
the time compared with 43% for acenocoumarol (OR 1.32, 95%
CI 1.24-1.41). Moreover, patients on phenprocoumon required
15% fewer monitoring visits and had more stable INR values.
These observations were consistent for all six clinics. There
were also sizable differences between the clinics with respect
to control and stability of anticoagulation that were stable from
year-to-year and were unrelated to the drug used.
With its longer half-life of three to five days, phenprocoumon
produces more stable anticoagulation than acenocoumarol and
should generally be the drug of choice when these are the avail-
able choices. The differences observed among clinics suggest
that certain clinics employ policies and practices resulting in
better control of anticoagulation.
Keywords
Anticoagulation, international normalised ratio, phenprocou-
mon, acenocoumarol
Summary
Variability in the control of oral anticoagulant therapy has been
associated with a heightened risk of complications. We com-
pared control of anticoagulation between two commonly used
coumarins, phenprocoumon and acenocoumarol, and among
anticoagulation clinics.
All qualifying patients were managed at six regional anticoagu-
lation clinics in the Netherlands.
This retrospective cohort study compiled data during a three-
year period from a computerised dosing and management system.
Anticoagulation control was expressed as the percent of time
within the therapeutic range and stability expressed as the time-
weighted variance in the international normalised ratio (INR).
Data were available for 22,178 patients of whom 72% were
treated with acenocoumarol. INRs of patients who received
Correspondence to:
Dr. Fihn
Northwest VA Health Services Research & Development Center of Excellence
VA Puget Sound Health Care System (152)
1660 S. Columbian Way
Seattle,WA 98108. USA
E-mail: sfihn@u.washington.edu
Received October 21, 2002
Accepted after revision March 19, 2003
Financial support:
This work was supported by a visitors grant from the
Nederlandse Organizatsie voor Wetenschappelijk Onderzoek.
DOI: 10.1160/TH02-10-0179
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
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