Compliance and stability of INR of two oral anticoagulants with different half-lives: a randomised trial

Summary

The aim of the study was to assess the respective roles of the half-life of elimination of oral anticoagulants and patient education as causes of instability of anticoagulation level in patients on oral anticoagulant therapy. Patients were randomised to receive either warfarin (long half-life) or acenocoumarol (short half-life) and either intensive or standard education, according to a factorial design. Instability of oral anticoagulant therapy was evaluated by the percentage of INRs and the time within the target range, and the variability between successive measurements. Compliance was assessed by means of electronic pill bottles. Eighty-six patients were included. Apart from the variability index, instability was similar between groups. Correlations between compliance and instability were observed only in the acenocoumarol group. No difference was found between the education groups. In patients starting oral anticoagulant therapy, dose determination may be the most important factor contributing to instability.

Keywords

Warfarin - acenocoumarol - compliance - instability - patient education

• References

• 1 Hirsh J, Dalen JE, Deykin D, Poller L. Oral anticoagulants: mechanism of action, clinical effectiveness and optimal therapeutic range. Chest 1992; 102: 312S-26S.
• 2 Albers GW, Dalen JE, Laupacis A, Manning WJ, Petersen P, Singer DE. Antithrombotic therapy in atrial fibrillation. Chest 2001; 119: 194S-206S. .
• 3 Mismetti P, Laporte-Simitsidis S, Tardy B, Queneau P, Decousus H. Prophylactic treatment of post-operative deep venous thrombosis in orthopaedic surgery of the hip with oral anticoagulant. Clin Trials Meta-analysis 1993; 28: 227-40.
• 4 Hull R, Raskob G, Pineo G, Rosenbloom D, Evans W, Mallory T, Anquist K, Smith F, Hughes G, Green D, Elliott G, Panju A, Brant R. A comparison of subcutaneous low molecular weight heparin with warfarin sodium for prophylaxis against deep vein thrombosis after hip or knee implantation. N Engl J Med 1993; 329: 1370-6.
• 5 Fihn SD, McDonnell M, Martin D, Henikoff Vermes D, Kent D, White R. for the Warfarin Optimised Outpatient Follow-up Study Group. Risk factors for complications of chronic anticoagulation. A multicenter study. Ann Intern Med 1993; 118: 511-21.
• 6 Levine MN, Raskob G, Landefeld S, Kearon C. Hemorrhagic complications of anticoagulant treatment. Sixth ACCP Consensus Conference on Antithrombotic Therapy. Chest 2001; 119: 108S-21S. .
• 7 Van der Meer FJ, Rosendaal FR, Vandenbroucke JP, Briët E. Bleeding complications in oral anticoagulant therapy: an analysis of risk factors. Arch Intern Med 1993; 153: 1557-62.
• 8 Cannegieter SC, Rosendaal FR, Wintzen AR, Van der Meer FJM, Vandenbroucke JP, Briët E. Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med 1995; 333: 11-7.
• 9 Berrettini M, Agnelli G. Management of oral anticoagulant therapy in Italy. Sem Thromb Haemost 1999; 25: 27-31.
• 10 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; 71: 188-91.
• 11 Barcellona D, Vannini ML, Fenu L, Balestrieri C, Marongiu F. Warfarin or Acenocoumarol: Which is better in the management of oral anticoagulants?. Thromb Haemost 1998; 80: 899-902.
• 12 Gadisseur AP, Van Der Meer FJM, 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.
• 13 Kumar S, Haigh JR, Tate G, Boothby M, Joanes DN, Davies JA, Roberts BE, Feely MP. Effect of warfarin on plasma concentrations of vitamin K dependent coagulation factors in patients with stable control and monitored compliance. Br J Haematol 1990; 74: 82-5.
• 14 Grymonpre RE, Didur CD, Montgomery PR, Sitar DS. Pill count, self-report, and pharmacy claims data to measure medication adherence in the elderly. Ann Pharmacother 1998; 32: 749-54.
• 15 Straka RJ, Fish JT, Benson SR, Suh JT. Patient self-reporting of compliance does not correspond with electronic monitoring: an evaluation using isosorbide dinitrate as a model drug. Pharmacotherapy 1997; 17: 126-32.
• 16 Federazione Centri Sorveglianza Anticoagulati. Nuova guida alla terapia con anticoagulanti orali Raccomandazioni della Federazione Centri Sorveglianza anticoagulati (FCSA). April 1996; 9-84.
• 17 Boneu B, Schved JF. Guide sur le traitement anticoagulant par voie orale (2e partie). Sang Thrombose Vaisseaux 1998; 6: 360-73.
• 18 Rosendaal FR, Cannegieter SC, Van der Meer FJM, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993; 69: 236-9.
• 19 Poller L, Shiach CR, Mac Callum PK, Johan-sen AM, Münster AM, Magalhães A, Jesper-sen J. on behalf of the European Concerted Action of Anticoagulation. Multicentre randomised study of computerised anticoagulant dosage. Lancet 1998; 352: 1505-9.
• 20 Van der Meer FJM, Briët E, Vandenbroucke JP, Sramek I D, Versluijs MHPM, Rosendaal FR. The role of compliance as a cause of instability in oral anticoagulant therapy. Br J Haematol 1997; 98: 893-900.
• 21 Byar DP, Piantadosi S. Factorial designs for randomized clinical trials. Cancer Treat Rep 1985; 69: 1055-63.
• 22 Kent DL, Vermes D, McDonell M, Henikoff J, Fihn SD. and the warfarin optimal outpatient follow-up study group. A model for planning optimal follow-up for outpatients on warfarin anticoagulation. Med Decis Making 1992; 12: 132-41.