Comparison of control and stability of oral anticoagulant therapy using acenocoumarol versus phenprocoumon

Stephan D. Fihn; Alain A. P. Gadisseur; Edwin Pasterkamp; Felix J. M. van der Meer; W. G. Mimi Breukink-Engbers; Lya M. Geven-Boere; Erik van Meegen; Hanneke de Vries-Goldschmeding; Irma Antheunissen-Anneveld; Annelies R. van’t Hoff; Derk Harderman; Margriet Smink; Frits R. Rosendaal

doi:10.1160/TH02-10-0179

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 90(02): 260-266
DOI: 10.1160/TH02-10-0179

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Comparison of control and stability of oral anticoagulant therapy using acenocoumarol versus phenprocoumon

Authors

Stephan D. Fihn

¹Northwest Health Services Research Center of Excellence, Veteran Affairs Puget Sound Health Care System

²Department of Medicine of the University of Washington, Seattle, Washington, USA
Alain A. P. Gadisseur

⁴Thrombosis Center of the Leiden University Medical Center
Edwin Pasterkamp

³Department of Clinical Epidemiology and Hemostasis and
Felix J. M. van der Meer

⁴Thrombosis Center of the Leiden University Medical Center
W. G. Mimi Breukink-Engbers

⁵Oostgelderland Anticoagulation Clinic, Lichtenvoorde
Lya M. Geven-Boere

⁶Leeuwarden Anticoagulation Clinic
Erik van Meegen

⁷Anticoagulation Clinic of the Hague
Hanneke de Vries-Goldschmeding

⁸Thrombosis Center of the Utrecht Division of the Dutch Red Cross
Irma Antheunissen-Anneveld

⁹Schiedam Anticoagulation Clinic
Annelies R. van’t Hoff

¹Northwest Health Services Research Center of Excellence, Veteran Affairs Puget Sound Health Care System
Derk Harderman

¹Northwest Health Services Research Center of Excellence, Veteran Affairs Puget Sound Health Care System
Margriet Smink

¹Northwest Health Services Research Center of Excellence, Veteran Affairs Puget Sound Health Care System
Frits R. Rosendaal

³Department of Clinical Epidemiology and Hemostasis and

⁴Thrombosis Center of the Leiden University Medical Center

Abstract

Summary

Variability in the control of oral anticoagulant therapy has been associated with a heightened risk of complications. We compared control of anticoagulation between two commonly used coumarins, phenprocoumon and acenocoumarol, and among anticoagulation clinics.

All qualifying patients were managed at six regional anticoagulation 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 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 available 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 - phenprocoumon - acenocoumarol

Full Text

References

References
1 Ansell J, Hirsh J, Dalen J. et al. Managing oral anticoagulant therapy. Chest 2001; 119: 22S-38S.
2 Hylek E, Singer DE. Risk factors for intra-cranial hemorrhage in outpatients taking war-farin. Ann Intern Med 1994; 120: 897-902.
3 Cannegieter SC, Rosendaal FR, Wintzen AR, van der Meer FJM, Vandenbroucke JP, Brië E. Optimal intensity of oral anticoagulation therapy in patients with mechanical heart valves. N Engl J Med 1995; 333: 11-7.
4 Hylek E, Skates SJ, Sheehan MA. et al. An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. N Engl J Med 1996; 335: 540-6.
5 Hirsh J, Dalen JE, Anderson DR, Poller L, Bussey H, Ansell J, Deykin D. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 2001; 119: 8S-21S.
6 Fihn SD, McDonell MB, Kent DL, Martin D, Henikoff JG. Vermes D and the warfarin anticoagulation follow-up study group. Risk factors for complications of chronic anticoagulation. A multicenter study. Ann Intern Med 1993; 118: 511-20.
7 Fihn SD, Callahan CM, Henikoff JG, McDonell MB, Martin D. for the National Consortium of Anticoagulation Clinics. The risk for and severity of bleeding complications in elderly patients treated with warfarin. Ann Intern Med 1996; 124: 970-9.
8 The Stroke Prevention in Atrial Fibrillation Investigators. Bleeding during antithrombotic therapy in patients with atrial fibrillation. Arch Intern Med 1996; 156: 40916.
9 Huber KC, Gersh BJ, Bailey KR, Schaff HV, Hodge DO, Ruth HC, Chesebro JH. Variability in anticoagulation control predicts thromboembolism after mechanical valve replacement: a 23-year population-based study. Mayo Clin Proc 1997; 72: 1103-10.
10 Casais P, Luceros AS, Meschengieser S, Fondevila C, Santarelli MT, Lazzari MA. Bleeding risk factors in chronic oral anticoagulation with acenocoumarol. Am J Hematol 2000; 63: 192-6.
11 Azar AJ, Dekkers JW, Rosendaal FR, van Bergen PF, van der Meer FJ, Jonker JJ, Brièt E. Assessment of therapeutic quality control in a long-term anticoagulant trial in post-myocardial infarction patients. Thromb Haemost 1994; 72: 347-51.
12 Kent DL, Vermes D, McDonell M, Henikoff J, Fihn SD. A model for planning optimal follow-up for outpatients on warfarin anticoagulation. Med Dec Making 1992; 12: 132-41.
13 Breed WPM, van Hooff JP, Haanen C. A comparative study concerning the stability of the anticoagulant effect of acenocoumarol and phenprocoumon. Acta Med Scand 1969; 186: 283-8.
14 Essnor RE, Peters HR. Experience with the anticoagulant marcumar. Ann Intern Med 1957; 47: 731-43.
15 Rodman T, Pastor BH, Resnick ME. Phenprocoumon, diphenadione, warfarin and bis-hydroxycoumarin: a comparative study. Amer J Med Sci 1964; 247: 655-64.
16 Fekkes N, De Jonge H, Veltkamp JJ, Bieger R, Loeliger A. Comparative study of the clinic effect of acenocoumarol (sintrom) and phenprocoumon in myocardial infarction and angina pectoris. Acta Med Scand 1971; 190: 535-40.
17 Thijssen HH, Hamulyak K, Willigers H. 4-Hydroxycoumarin oral anticoagulants: phar-macokinetics-response relationship. Thromb Haemost 1988; 60: 35-8.
18 Barcellona D, Vannini ML, Fenu L, Balesteri C, Marongiu F. Warfarin or acenocoumarol: which is better in the management of oral anticoagulants?. Thromb Haemost 1998; 80: 899-902.
19 Amian A, Rodrique JN, Muniz R. et al. Comparative study of the stability of oral anticoagulant treatments (warfarin vs. acenocoumarol). Sangre (Barc) 1996; 41: 9-11.
20 Pattacini C, Manotti C, Pini M, Quintavalla R, Dettori AG. A comparative study on the quality of oral anticoagulant therapy (warfarin versus acenocoumarol). Thromb Haemost. 1994: 188-91.
21 van der Meer FJM, Briët E, Vandenbrouke JP, Šrámek DI, Versluijs MHPM, Rosendaal FR. The role of compliance as a cause of instability in oral anticoagulant therapy. Br J Haematol 1997; 98: 893-900.
22 Kamali F, Edwards C, Butler TJ, Wynne HA. The influence of (R)- and (S)-warfarin, vitamin K, and vitamin K epoxide levels upon warfarin anticoagulation. Thromb Haemost 2000; 84: 39-42.
23 van der Meer FJ, Rosendaal FR, Vandenbrouke JP, Briët E. Bleeding complications in oral anticoagulant therapy: An analysis of risk factors. Arch Intern Med 1993; 153: 1557-62.
24 Thijssen HHW, Hemker HC. Orale antistollingsbehandeling; welk anticoagulans?. Ned Tidjschr Geneeskd 1984; 128: 1159-63.
25 Shetty HG, Backhouse G, Bentley OP. et al. Effective reversal of warfarin-induced excessive anticoagulation with low dose vitamin K1. Thromb Haemost 1992; 67: 13-15.
26 Raj G, Kumar R, McKinney P. Time course of reversal of anticoagulant effect of warfarin by intravenous and subcutaneous phytonadione. Arch Intern Med 1999; 159: 2721-4.
27 Pengo V, Banzato A, Garelli E. et al. Reversal of excessive effect of regular anticoagulation: low oral dose of phytonadione (vitamin K1 ) compared with warfarin discontinuation. Blood Coagul Fibrinolysis 1993; 4: 739-41.
28 Weibert RE, Le DT, Kayser SR. et al. Correction of excessive anticoagulation with low dose oral vitamin K1. Ann Intern Med 1997; 125: 959-62.
29 Crowther MA, Donovan D, Harrison L. et al. Low dose oral vitamin K reliably reverses over anticoagulation due to warfarin. Thromb Haemost 1998; 79: 1116-8.