약학회지 (YAKHAK HOEJI)

  • 제53권2호
  • /
  • Pages.83-88
  • /
  • 2009
  • /
  • 0377-9556(pISSN)
  • /
  • 2383-9457(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

뇌졸중 환자군의 Warfarin Nomogram 설정을 위한 실제 처방전 평가

Evaluation of Prescription Data for Development of Warfarin Nomogram in Korean Patients with Cerebral Infarction

  • 장주영 (가톨릭대학교 강남성모병원 약제팀) ;
  • 고경미 (가톨릭대학교 강남성모병원 약제팀) ;
  • 윤지연 (가톨릭대학교 강남성모병원 약제팀) ;
  • 한옥연 (가톨릭대학교 강남성모병원 약제팀) ;
  • 임성실 (충북대학교 약학대학)
  • Jang, Ju-Young (Department of Pharmacy, Kangnam ST, Mary's Hospital, The Catholic University of Korea) ;
  • Ko, Kyung-Mi (Department of Pharmacy, Kangnam ST, Mary's Hospital, The Catholic University of Korea) ;
  • Yoon, Ji-Yeon (Department of Pharmacy, Kangnam ST, Mary's Hospital, The Catholic University of Korea) ;
  • Han, Ok-Yeon (Department of Pharmacy, Kangnam ST, Mary's Hospital, The Catholic University of Korea) ;
  • Lim, Sung-Cil (College of Pharmacy, CBITRC, Chungbuk National University)
  • 발행 : 2009.04.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Warfarin is the most widely used oral anticoagulant in the world but maintenance of proper therapeutic range and prevention of adverse drug events always need to be careful. Especially, in Korea, warfarin dosing for patients with cerebral infarction is currently based on the nomogram which is done by foreign clinical trials not for the Korean. Therefore we evaluate warfarin dose of patients in the neurology and eventually get the base data of warfarin nomogram for Korean with stroke. We performed this study retrospectively on reviewing the medical charts to evaluate the prescribed loading dose (LD) and maintenance dose (MD) of warfarin and each responding International Normalized Ratio (INR) with any bleeding adverse drug reaction including of patient's characteristics for total 75 patients with stroke in the department of neurology of Kangnam ST. Mary's Hospital from January 2005 to June 2008. All evaluated patients should not be treated with warfarin in the past at all and should be initiated warfarin therapy first.ly at this time. All evaluated patients were divided as two classes by wafarin LD which is; 1) HDG - a high loading dosing group prescribed over 5mg, and 2) LDG - a low loading dosing group prescribed 5mg or below. As a result, average LD was $9.34{\pm}0.22$ mg (p=0.000) in HDG and $4.25{\pm}0.39$ mg (p=0.000) in LDG. Average baseline INR was $0.91{\pm}0.05$ (p=0.161) in HDG and $1.26{\pm}0.14$ (p=0.002) in LDG. On the first and second week, daily MD was $4.21{\pm}0.14$ mg (p=0.000) and $2.96{\pm}0.19$ mg (p=0.696) in HDG and also in LDG, $2.95{\pm}0.29$ mg (p=0.000) and $3.14{\pm}0.36$ mg (p=0.696). Also average reacting daily INR was respectively $2.53{\pm}0.12$ (p=0.141) and $2.51{\pm}0.16$ (p=0.678) in HDG, and in LDG, $2.11{\pm}0.17$ (p=0.141) and $2.42{\pm}0.14$ (p=0.678). After the second week, INR was not measured in regularly. Also most of underlying diseases were hypertension (n=38), diabetes mellitus (n=14), dyslipidemia (n=8) in order. Four ADRs with simple hemorrhage were occurred and those were due to drug interaction by comedication. In the conclusion, proper starting LD for Korean with stroke is 10 mg if baseline INR is around 1.0 or 5 mg if over 1.3. Proper MD need to be more evaluated in the future for setting up warfarin nomogram to make prospective study.

키워드

참고문헌

  1. American Society of Health-system. AHFS Drug Information, Iron Preparations. 1458 (2008)
  2. David, A. Garcia MD, Elaine M. Hylek MD, MPH. : Antithrombotic therapy in atrial fibrillation. Clin. Geriar. Med. 22, 155 (2006) https://doi.org/10.1016/j.cger.2005.09.011
  3. Furie, K. L., Rosenberg, R., Thompson, J. L., Bauer, K., Mohr, J. P., Rosner, B., Sciacca, R., Barzegar, S., Thornell, B., Costigan, T. and Kistler, J. P. : Thrombin generation in noncardioembolic stroke subtypes: the hemostatic system activation study. Neurology 63, 768 (2004) https://doi.org/10.1212/01.WNL.0000140034.85426.D7
  4. Garcia, D. A. and Hylek, E. : Reducing the risk for stroke in patients who have atrial fibrillation. Cardiol. Clin. 26, 267 (2008) https://doi.org/10.1016/j.ccl.2007.12.011
  5. Goldstein, J. N., Thomas, S. H., Frontiero, V., Joseph, A., Engel, C., Snider, R., Smith, E. E., Greenberg, S. M. and Rosand, J. : Timing of fresh frozen plasma administration and rapid correction of coagulopathy in warfarin-related intracerebral hemorrhage. Stroke. Jan. 37, 151 (2006) https://doi.org/10.1161/01.STR.0000195047.21562.23
  6. Hankey, G. J. and Warlow, C. P. : Treatment and secondaryprevention of stroke: evidence, costs, and effects on individuals and populations. Lancet 354, 1457 (1999) https://doi.org/10.1016/S0140-6736(99)04407-4
  7. Ng, P. W. : The stroke epidemic. Hong Kong Med. J. 13, 92 (2007)
  8. Anderson David R, Wilson S. Jo-Anne, Blundell Jennifer, Petrie David, Leighton Ross, Stanish William, Allexander David, Robinson K. Sue, Burton Erica, Gross Michael. : Comparsion of a nomogramand physician-adjusted dosage of warfarin for prophylaxis against deep-vein thrombosis after Arthroplaty. J. Bone Joint Surg Am. 84, 1992 (2002) https://doi.org/10.2106/00004623-200211000-00013
  9. Kovacs, M. J., Rodger, M., Anderson, D. R., Morrow, B., Kells, G., Kovacs, J., Boyle, E. and Wells, P. S. : Comparison of 10-mg and 5-mg warfarin initiation nomograms together with lowmolecular- weight heparin for outpatient treatment of acute venous thromboembolism. A randomized, double-blind, controlled trial. Ann. 138, 714 (2003)
  10. Wada, Y., Mizushige, K., Ohmori, K., Iwado, Y., Kohno, M. and Matsuo, H. : Prevention of cerebral thromboembolism by lowdose anticoagulant therapy in atrial fibrillation with mitral regurgitation. J. Cardiovasc. Pharmacol. 37, 422 (2001) https://doi.org/10.1097/00005344-200104000-00009
  11. Lee, B. K. : Analysis of factors affecting nontherapeutic INRs and determination of practical dosing of warfarin in Korean outpatients with mechanical heart valves. Dept. of Pharmacy graduate school, Chungbuk National University Cheong ju, Korea (2002)
  12. Yamaguchi, T. : Optimal intensity of warfarin therapy for secondary prevention of stroke in patients with nonvalvular atrial fibrillation : a multicenter, prospective, randomized trial. Japanese nonvalvular atrial fibrillation-embolism secondary prevention cooperative study group. Stroke 817 (2000)
  13. Zhou, J.-M., Liu, S.-W., Lin, J.-X., Nie, Z.-N., Wu, H.-Y., Zhou, J., Hao, Y., Cai, N.-S. and Ge, J.-B.. : Thromboembolic event rate in patients with persistent or paroxysmal atrial fibrillation post circumferential pulmonary vein isolation: a single center experience in China. China Med. J. 120, 956 (2007)
  14. Banet, G. A., Waterman, A. D., Milligan, P. E., Gatchel, S. K. and Gage, B. F. : Warfarin dose reduction vs watchful waiting for mild elevations in the international normalized ratio. Chest. 123, 499 (2003) https://doi.org/10.1378/chest.123.2.499
  15. Franke, C. A., Dickerson, L. M. and Carek, P. J. : Improving anticoagulation therapy using point-of-care testing and a standardized protocol. Ann. Fam. Med. 1, 28 (2008)
  16. Kim, H. J., Pak, H. M., Kim, J. M. and Sohn, K. H. : Evaluation of warfarin initial dosing in korean patients. J. Kor. Soc. Health- Syst. Pharm. 23, 104 (2006)
  17. Hertzberg, V., Chimowitz, M., Lynn, M., Chester, C., Asbury, W. and Cotsonis, G. : Use of dose modification schedules is effective for blinding trials of warfarin: evidence from the WASID study. Clin Trials 5, 23 (2008) https://doi.org/10.1177/1740774507087781
  18. Nam, J. Y., Choi, K. S., Jeong, Y. M., Namgung, H. W. and Lee, B. K. : Warfarin maintenance dosages in very elderly Korean patients. J. Kor. Soc. Health-Syst. Pharm. 24, 196 (2007)
  19. Roberts, G. W., Herboe, T., Nislsen, C. B. M., et al. : Assessment of an age-adjusted warfarin initiation protocol. Annals of Pharmacotherapy 37, 799 (2003) https://doi.org/10.1345/aph.1A372
  20. Caldwell, M. D., Berg, R. L., Zhang, K. Q., Glurich, I., Schmelzer, J. R., Yale, S. H., Vidaillet, H. J. and Burmester, J. K. : Evaluation of genetic factors for warfarin dose prediction. Clin. Med. Res. 5, 8 (2007) https://doi.org/10.3121/cmr.2007.724
  21. Lee, S.-Y., Nam, M.-H., Kim, J. S. and Kim, J.-W. : A case report carrying CYP2C9*3/4 genotype with extremely low warfarin dose resuirement. J. Korean Med. Sci. 22, 557 (2007) https://doi.org/10.3346/jkms.2007.22.3.557
  22. Veenstra, D. L., You, J. H., Rieder, M. J., Farin, F. M., Wilkerson, H. W., Blough, D. K., Cheng, G. and Rettie, A. E. : Association of Vitamin K epoxide reductase complex 1 (VKORC1) variants with warfarin dose in a Hong Kong Chinese patient population. Pharmacogenet Genomics 10, 687 (2005)