Journal of Chest Surgery

The Korean Society for Thoracic and Cardiovascular Surgery (대한심장혈관흉부외과학회)
권호 표지

Analysis of Factors Affecting Nontherapeutic INRs in Korean Outpatients with Mechanical Heart Valves

인공심장판막 치환환자의 치료범위를 벗어난 INR 원인분석

  • Lee Ju Yeun (Department of Pharmacy, Seoul National University Hospital) ;
  • Jeong Young Mi (Department of Pharmacy, Seoul National University Bundang Hospital) ;
  • Lee Myung Koo (College of Pharmacy, Chungbuk National University) ;
  • Kim Ki-bong (Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital) ;
  • Ahn Hyuk (Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital) ;
  • Lee Byung Koo (Department of Pharmacy, Seoul National University Bundang Hospital)
  • 이주연 (서울대학교병원 약제부) ;
  • 정영미 (분당서울대학교병원 약제부) ;
  • 이명구 (충북대학교 약학대학) ;
  • 김기봉 (서울대학교병원 흉부외과) ;
  • 안혁 (서울대학교병원 흉부외과) ;
  • 이병구 (분당서울대학교병원 약제부)
  • Published : 2005.11.01
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Following the implantation of heart valve prostheses, it is important to maintain therapeutic INR to reduce the risk of thromboembolism. The objectives of this study were to determine the causes of nontherapeutic INRs, and to identify the factors associated with nonadherences to warfarin therapy in Korean outpatients with prosthetic heart valves managed by a pharmacist-run anticoagulation service (ACS). Material and Method: A retrospective chart review was completed for all patients enrolled in the ACS at Seoul National University Hospital from March, 1997b to September, 2000. The data on 868 patients (5,304 visits) who were at least 6 months post-valve replacement were included. All possible causes of nontherapeutic INRs were documented for each patient visit. The association of covariates to noncompliance was investigated by univariate analysis. Result: The reasons for nontherapeutic INRs were identified as follows: inadequate dosage adjustment $(21\%)$, nonadherences to dosing regimen $(13\%)$, drug/herbal interactions $(12\%)$, changes in diet $(7\%)$, and indeterminate cause $(42\%)$. Younger age, shorter duration of ACS and longer duration of warfarin therapy were associated with nonadherence. Conclusion: In this study, nonadherence and interactions between diet and medications were found to be important factors influencing nontherapeutic INRs. Longer duration of enrollment in the ACS affected the adherence to warfarin therapy Positively whereas younger age and longer duration of warfarin therapy affected negatively.

배경: 인공심장판막 시술 후에 환자들은 혈전색전증의 위험성을 감소시키기 위해서 평생 warfarin투여를 받게 된다 한국인 환자에서 목표 INR 2.0-3.0을 유지하는 것은 여러 가지 이유로 어려움이 따른다. 이 연구의 목적은 약사에 의해서 운영되는 anticoagulation service (ACS)을 받는 한국 인공심장판막 외래환자에서 치료 범위를 벗어난 INR의 원인을 분석하고 warfarin치료에의 복약불이행과 관련된 요인들을 확인하고자 하였다. 대상 및 방법: 1997년 3월에서 2000년 9월까지 서울대학교병원에서 ACS를 방문한 모든 환자의 의무기록을 후향적으로 검토하였다. 수술 후 6개월이 경과된 화자로 INR 2.0 미만과 INR 3.0초과가 한 번 이상 있는 환자 866명(5,304회 방문)을 대상으로 치료 범위를 벗어난 INR의 가능한 모든 원인들을 환자 방문 때마다 분석하였다 성별, 연령, ACS 상담을 받은 기간 및 warfarin 치료 기간과 복약불이행과의 상관성은 단변수 분석으로 확인하였다. 걸과· 비치료범위의 INR의 원인은 다음과 같았다: 부적절한 용량 조절$(21\%)$, 복약불이행$(13\%)$, 약물-약물/한약 상호작용$(12\%)$, 식이의 변화$(7\%)$, 확인불가$(42\%)$. 낮은 연령, 짧은 ACS 상담 기간, 장기간의 warfarin 치료가 복약불이행과 관련이 있었다 결론: 이 연구에서 복약불이행, 약물과 식이의 상호작용이 비치료범위의 INR의 중요한 요인임이 확인되었다. 낮은 연령과 장기간의 warfarin치료 기간이 복약불이행과 상관이 있었던 반면 ACS 등록된 기간이 길수록 warf arin에 대한 치료 순응도가 높아졌다.

Keywords

References

  1. Tiede DJ, Nishimura RA, Gastineau DA, et al. Modern management of prosthetic valve anticoagulation. Mayo Clin Proc 1998;73:665-80 https://doi.org/10.4065/73.7.665
  2. Jack Hirsh. Oral anticoagulants: Mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 2001; 119:8S-21S https://doi.org/10.1378/chest.119.1_suppl.8S
  3. Gage BF, Fihn SD, White RH. Management and dosing of warfarin therapy. Am J Med 2000;109:481-8 https://doi.org/10.1016/S0002-9343(00)00545-3
  4. Rose JP, Rihn TL, Long SF. Warfarin sensitivity after mechanical heart valve replacement. Pharmacotherapy 1998;18: 856-9
  5. Cannegieter SC, Rosendaal FR, Wintzen AR, et al. The optimal intensity of oral anticoagulant therapy in patients with mechanical heart valve prosthese: the Leiden artificial valve and anticoagulation study. N Engl J Med 1995;333:11-7 https://doi.org/10.1056/NEJM199507063330103
  6. Ansell J, Hirsh J, Dalen J, Bussey H, Anderson D, Poller L, Jacobson A, Deykin D. Managing oral anticoagulant therapy. Chest 2001;119:22S-38S https://doi.org/10.1378/chest.119.1_suppl.22S
  7. Chong Whan Kim,Young Tae Kim. Anticoagulation management after mitral valve replacement with St. Jude medical prosthesis. Korean J Thorac Cardiovasc Surg 1998;31:1172- 82
  8. Davis FB, Estruch MT, Samson-Cervera EB, et al. Management of anticoagulation in outpatients: Experience with an anticoagulation service in a municipal hospital setting. Arch Intern Med 1977;137:197-202 https://doi.org/10.1001/archinte.137.2.197
  9. Lee BK. The current state and future plans of anticoagulation service (ACS). Proceedings of the 7th Midyear Clinical Meeting of The Korean Society of Health-system Pharmacists 2001
  10. Jeong YM, Lee BK, Ahn H. Quality assurance program for anticoagulation service. Proceedings of the 3rd Quality Assurance Conference, Seoul National University Hospital 1997
  11. Kim CW, Kim YT. Anticoagulation in patients with St. jude medical prosthesis. Korean J Thorac Cardiovasc Surg 1998;31:684-91
  12. Brigden ML, Kay CLA, Graydon C, McLeod B. Audit of the frequency and clinical response to excessive oral anticoagulation in an out-patient population. Am J Hematol 1998;59:22-7 https://doi.org/10.1002/(SICI)1096-8652(199809)59:1<22::AID-AJH5>3.0.CO;2-1
  13. Lousberg TR, Witt DM, Beall DG, et al. Evaluation of excessive anticoagulation in a group model health maintenance organization. Arch Intern Med 1998;158:528-34 https://doi.org/10.1001/archinte.158.5.528
  14. Fihn SD, McDonell M, Martin D, Henikoffs, Vermes D, Kent D, White RH. Risk factors for complications of chronic anticoagulation: A multicenter study. Ann Intern Med 1993;118:511-20 https://doi.org/10.7326/0003-4819-118-7-199304010-00005
  15. Lee HJ, Hahn HJ, Park KH, Lee BK, Cho NC, Shin WG. The degree of patient's understanding and teaching & counseling for warfarin therapy. J Korean Health-System Phrm 1996;13:341-6
  16. Kumar S, Haigh JR, Rhodes LE, et al. Poor compliance is a major factor in unstable outpatient control of anticoagulant therapy. Thromb Haemeost 1989;62:729-32
  17. Wong W, Wilson NJ, Wittkowsky AK. Influence of warfarin regimen type on clinical and monitoring outcomes in stable patients in an anticoagulation management services. Pharmacotherapy 1999;19:1385-91 https://doi.org/10.1592/phco.19.18.1385.30894
  18. Arnsten JH, Gelfand JM, Singer DE. Determinants of compliance with anticoagulation: a case-control study. Am J Med 1997;103:11-7 https://doi.org/10.1016/S0002-9343(97)90048-6
  19. Kerin NZ, Blevins RD, Goldman L, Faitel K, Rubenfire M. The incidence, magnitude, and time course of the amiodarone-warfarin interaction. Arch Intern Med 1988;148: 1779-81 https://doi.org/10.1001/archinte.148.8.1779
  20. Thomas YK Chan. Adverse interactions between warfarin and nonsteroidal antiinflammatory drugs: Mechanisms, clinical significance, and avoidance. Ann Pharmacother 1995;29: 1274-83 https://doi.org/10.1177/106002809502901214
  21. Cropp JS, Bussey HI. A review of enzyme induction of warfarin metabolism with recommendations for patient management. Pharmacotherapy 1997;17:917-28
  22. Heck AM, Dewitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-7
  23. Janetzky K, Morreale AP. Probable interaction between warfarin and ginseng. Am J Heath-syst Pharm 1997;54:692-3
  24. Taylor JR, Wilt VM. Probable antagonism of warfarin by green tea. Ann Pharmacother 1999;33:426-8 https://doi.org/10.1345/aph.18238
  25. Booth SL, A. Centurelli MA. Vitamine K: A practical guide to the dietary management of patients on warfarin. Nutrition Reviews 1999;57:288-96 https://doi.org/10.1111/j.1753-4887.1999.tb01815.x
  26. Goodnight SH. Physiology of coagulation and the role of vitamin K. Managing oral anticoagulation therapy: Clinical and operational guidelines. Gaithersburg, Maryland; An Aspen Publication, 1997:1B-1:1-1B-1:9
  27. Seo JA, Jeong YM, Chung SY, Kim YJ, Lee BK, Cho NC, Ahn H. Management of warfarin in patients with prosthetic heart valves before dental procedure. The 19th Annual Convention of the Korean Society of Hospital Pharmacists 1999:266-7
  28. Souto JC, Olover A, Zuazu-Jausoro I, Vives A, Foncuberta J. Oral surgery in anticoagulated patients without reducing the dose of oral anticoagulant: A prospective randomized study. J Oral Maxillofoc Surg 1996;54:27-32 https://doi.org/10.1016/S0278-2391(96)90297-9
  29. Demirkan K, Stephens MA, Newman KP, Self TH. Response to warfarin and other oral anticoagulants: Effects of disease states. South Med J 2000;93:448-54 https://doi.org/10.1097/00007611-200093050-00001