Correlation Between Warfarin Levels in the Blood and the Value of Normal INR in Fibrillation Atrium Inpatients

https://doi.org/10.22146/jmpf.89898

Masita Wulandari Suryoputri(1*), Nialiana Endah Endriastuti(2), Dewi Latifatul Ilma(3), Alfita Azzahra(4)

(1) Department of Pharmacy, Faculty of Health Sciences, Jenderal Soedirman University, Central Java
(2) Department of Pharmacy, Faculty of Health Sciences, Jenderal Soedirman University, Central Java
(3) Department of Pharmacy, Faculty of Health Sciences, Jenderal Soedirman University, Central Java
(4) Department of Pharmacy, Faculty of Health Sciences, Jenderal Soedirman University, Central Java
(*) Corresponding Author

Abstract


Background: Warfarin is an anticoagulant inhibitor of vitamin K that is effective in preventing systemic embolization in atrial fibrillation patients. Warfarin has a narrow therapeutic index, so it requires monitoring of rates to prevent the occurrence of toxic effects and to ensure the passage of INR values.

Objectives: The study aims to find out the correlation between warfarin levels and normal INR values.

Methods: Observational research method with the collection of retrospective data on the medical records of patients treated with atrial fibrillation at Prof. Dr. Margono Soekarjo Hospital, Purwokerto, in January 2019–December 2021. Warfarin levels were calculated pharmacokinetically using the steady-state concentration (Css) and plasma concentration (Cp) formulas. Data analysis is carried out using the Spearman test to determine the correlation between warfarin levels and normal INR values.

Results: The number of patients with normal INR values was less than the number of patients with abnormal INR values, namely 21 patients and 48 patients. The Spearman test results show a p-value of 0.31 (p>0.05), showing that the correlation between warfarin levels in the blood and the corresponding INR value is not significant (p> 0.05), and the R value in the Spearman test is 0.122, showing that the direction of the correlation is positive with very weak correlation strength.

Conclusion: The correlation between warfarin levels in the blood and the appropriate INR value is not significant (p>0.05), where the R value in the Spearman test shows R=0.122, meaning the direction of the correlation is positive with a very weak correlation strength.

Keywords


atrial fibrillation; INR; warfarin levels

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References

  1. Siontis, K. C., Geske, J. B. and Gersh BJ. Atrial Fibrillation Pathophysiology and Prognosis: Insights From Cardiovascular Imaging. Circ Cardiovasc Imaging. 2015;8(6):3020. doi:doi: 10.1161/CIRCIMAGING.115.003020.
  2. Hindricks, G., Potpara, T., Dagres, N., Arbelo, E., Bax, J.J., Blomström-Lundqvist, C., Boriani, G., Castella, M., Dan, G.A., Dilaveris, P.E., Fauchier, L., Filippatos, G., Kalman, J.M., La Meir, M., Lane, D.A., Lebeau, J.P., Lettino, M., Lip, G., Pinto, C. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Hear Journal,. 2021;42(5):373-498. doi:doi: 10.1093/eurheartj/ehaa612.
  3. Lippi, G., Sanchis-Gomar, F. and Cervellin G. Global epidemiology of atrial fibrillation: An increasing epidemic and public health challenge. Int J Stroke. 2021;16(2):217-221. doi:doi: 10.1177/1747493019897870.
  4. Nesheiwat Z, Goyal A JM. Atrial Fibrillation [Updated 2022 May 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Published 2022. https://www.ncbi.nlm.nih.gov/books/NBK526072/
  5. Zimetbaum P. Atrial Fibrillation. Ann Intern Med. 2017;166(5):33. doi:doi: 10.7326/AITC201703070.
  6. Brunton, L. L., Knollmann, B. C., & Hilal-Dandan R. Goodman & Gilman’s the Pharmacological Basis of Therapeutics. Thirteenth. McGraw Hill Medical.; 2018.
  7. Yakobus Y. New oral anticoagulants for Atrial Fibrillation. Indones J Med Heal. 2017;8(2):102-109. doi:https://doi.org/10.20885/JKKI.Vol8.Iss2.art5
  8. Furdiyanti, N. H., Pramantara, I. D. P., & Wahyono D. ‘Evaluasi Dosis Warfarin dan Hasil Terapinya pada Pasien Rawat Jalan. J Manag Pharm Pract. 2014;4(3):175-179.
  9. Zeid Nesheiwat; Amandeep Goyal; Mandar. Atrial Fibrillation. Updated 20. (In: StatPearls, ed.). StatPearls Publishing; 2022. https://www.ncbi.nlm.nih.gov/books/NBK526072/
  10. Suryoputri MW, Mustikaningtias I, Maharani L. Pemantauan Kadar Obat Indeks Terapi Sempit Melalui Estimasi Kadar Obat di Dalam Darah pada Pasien Rawat Inap di RSUD Prof. Dr. Margono Soekarjo, Purwokerto. Indones J Clin Pharm. 2020;9(2):105. doi:10.15416/ijcp.2020.9.2.105
  11. Rowland, M., dan Tozer TN. Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Applications. edisi 4. Wolters Kluwer Health/Lippincott William & Wilkins, Philadelphia.; 2011.
  12. Katzung, B. G., Trevor, A., & Kruidering-Hall M. Katzung & Trevor’s Pharmacology: Examination & Board Review (. 13th ed. McGraw-Hill Education.; 2015.
  13. Chung, M. K., Refaat, M., Shen, W.-K., Kutyifa, V., Cha, Y.-M., Di Biase, L., Baranchuk, A., Lampert, R., Natale, A., Fisher, J., & Lakkireddy DR. Atrial Fibrillation. J Am Coll Cardiol. 2020;75(14):1689–1713. doi:https://doi.org/10.1016/j.jacc.2020.02.025
  14. Westerman, S., & Wenger, N. Gender Differences in Atrial Fibrillation: A Review of Epidemiology, Management, and Outcomes. Curr Cardiol Rev. 2019;15(2):136–144. doi:https://doi.org/10.2174/1573403X15666181205110624
  15. Bouzas-Mosquera, A., Broullon, F. J., Alvarez-Garcia, N., Mendez, E., Peteiro, J., Gandara-Sambade, T., Prada, O., Mosquera, V. X., & Castro-Beiras A. Left atrial size and risk for all-cause mortality and ischemic stroke. Can Med Assoc J. 2011;183(10):E657–E664. doi:https://doi.org/10.1503/cmaj.091688
  16. Odening, K. E., Deiß, S., Dilling-Boer, D., Didenko, M., Eriksson, U., Nedios, S., Ng, F. S., Roca Luque, I., Sanchez Borque, P., Vernooy, K., Wijnmaalen, A. P., & Yorgun, H. Mechanisms of sex differences in atrial fibrillation: Role of hormones and differences in electrophysiology, structure, function, and remodelling. EP Eur. 2019;21(3):366–376. doi:https://doi.org/10.1093/europace/euy215
  17. Di Benedetto, L., Michels, G., Luben, R., Khaw, K.-T., & Pfister R. Individual and combined impact of lifestyle factors on atrial fibrillation in apparently healthy men and women: The EPIC-Norfolk prospective population study. Eur J Prev Cardiol. 2018;25(13):1374–1383. doi:https://doi.org/10.1177/2047487318782379
  18. Morseth, B., Geelhoed, B., Linneberg, A., Johansson, L., Kuulasmaa, K., Salomaa, V., Iacoviello, L., Costanzo, S., Söderberg, S., Niiranen, T. J., Vishram-Nielsen, J. K. K., Njølstad, I., Wilsgaard, T., Mathiesen, E. B., Løchen, M.-L., Zeller, T., Blanken RB. Age-specific atrial fibrillation incidence, attributable risk factors and risk of stroke and mortality: Results from the MORGAM Consortium. Open Hear. 2021;8(2):1624. doi:https://doi.org/10.1136/openhrt-2021-001624
  19. Mandalenakis, Z., Von Koch, L., Eriksson, H., Dellborg, M., Caidahl, K., Welin, L., Rosengren, A., & Hansson P-O. The risk of atrial fibrillation in the general male population: A lifetime follow-up of 50-year-old men. Europace. 2015;17(7):1018–1022. doi:https://doi.org/10.1093/europace/euv036
  20. R. A. Bimandoko, P. Ardhianto and HM. HUBUNGAN FIBRILASI ATRIUM TERHADAP PENURUNAN FUNGSI KOGNITIF. J Kedokt Diponegoro. 2016;5(4):1693-1700. doi:https://doi.org/10.14710/dmj.v5i4.15917
  21. Shendre, A., Parmar, G. M., Dillon, C., Beasley, T. M., & Limdi NA. Influence of Age on Warfarin Dose, Anticoagulation Control, and Risk of Hemorrhage. Pharmacother J Hum Pharmacol Drug Ther. 2018;38(6):588-596. doi:https://doi.org/10.1002/phar.2089
  22. Naser, N., Dilic, M., Durak, A., Kulic, M., Pepic, E., Smajic, E., & Kusljugic, Z. The Impact of Risk Factors and Comorbidities on The Incidence of Atrial Fibrillation. Mater Socio Medica. 2017;29(4):231-236.
  23. Sugumar, H., Nanayakkara, S., Prabhu, S., Voskoboinik, A., Kaye, D. M., Ling, L.-H., & Kistler, P. M. Pathophysiology of Atrial Fibrillation and Heart Failure. Cardiol Clin. 2019;37(2):131-138. doi:https://doi.org/10.1016/j.ccl.2019.01.002
  24. Diaz, J., Martinez, F., Calderon, J. M., Fernandez, A., Sauri, I., Uso, R., Trillo, J. L., Redon, J., & Forner, M. J. Incidence and impact of atrial fibrillation in heart failure patients: Real‐world data in a large community. ESC Hear Fail. 2022;9(6):4230–4239. doi:https://doi.org/10.1002/ehf2.14124
  25. BPOM. Antikoagulan Oral. Published 2023. Accessed November 3, 2023. https://pionas.pom.go.id/ioni/bab-2-sistem-kardiovaskuler-0/26-antikoagulan-dan-protamin/261-antikoagulan-oral
  26. Effendi. Tatalaksana Fibrilasi Atrium. Cermin Dunia Kedokt J. 2017;44(2):93-96.
  27. Hirsh, J., Fuster, V., Ansell, J., & Halperin, J. L. Circulation. Am Hear Assoc Coll Cardiol Found Guid to Warfarin Ther. 2003;107(12):1692–1711. doi:https://doi.org/10.1161/01.CIR.0000063575.17904.4
  28. Ashorobi, D., Ameer, M. A., & Fernandez R. Thrombosis. StatPearls Publishing. Published 2023. https://www.ncbi.nlm.nih.gov/books/NBK538430/
  29. Wallace JL, Reaves AB, Tolley EA, Oliphant CS, Hutchison L, Alabdan NA, Sands CW ST. Comparison of initial warfarin response in obese patients versus non-obese patients. J Thromb Thrombolysis. 2013;36(1):96-101. doi:doi: 10.1007/s11239-012-0811-x. PMID: 23015280.
  30. Holbrook, A., Schulman, S., Witt D. M., Vandvik, P. O., Fish, J., Kovacs MJ et al. Evidence-Based Management of Anticoagulant Therapy: Antithrombotic Therapy and Prevention of Thrombosis. Am Coll Chest Physicians Evidence-Based Clin Pract Guidel. 2012;141(2):152-184.
  31. Rusdiana, T., Araki, T., Nakamura, T., Subarnas, A., dan Yamamoto, K. Responsiveness to Low-Dose Warfarin Associated with Genetic Variants of VKORC1, CYP2C9, CYP2C19, and CYP4F2 in an Indonesian Population. Eur J Clin Pharmacol. 2013;69(3):395–405.
  32. Clarke, R., Ross, S., Walker, T., dan Woods D. INR Testing.; 2006.
  33. Patel S, Singh R PC. Warfarin [Updated 2022 Mar 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Published 2022. https://www.ncbi.nlm.nih.gov/books/NBK470313/
  34. Shargel, L & Yu AB. Applied Biopharmaceutics and Pharmacokinetics. Seventh. McGraw-Hill Companies.; 2016.
  35. Rahmatini, R., Aliska, G., Usman, E., Yanni, M., & Ilmiawati, C. Plasma Warfarin Level and International Normalized Ratio do not Correlate with Bleeding Events in Indonesian Patients of Minangkabau Ethnicity with Atrial Fibrillation. Open Access Maced J Med Sci. 2020;8(B):192-197. doi:https://doi.org/10.3889/oamjms.2020.3436
  36. Lingga HN, Hakim L PI. Evaluasi dosis asam valproat pada pasien epilepsi anak. J Manag Pharm Pr. 2013;3(2):137–42. doi:doi: 10.22146/jmpf.112
  37. Clarke W DA. Clinical Challenges in Therapeutic Drug Monitoring: Special Populations, Physiological Conditions, and Pharmacogenomics.; 2016.
  38. Methaneethorn J. A systematic review of population phramacokinetics of valproid acid. Br J Clin Pharmacol. 2018;84(5):816-834. doi:doi: 10.1111/bcp.13510
  39. Patel S, Singh R PC. Warfarin [Updated 2022 Mar 13]. Treasure Isl StatPearls Publ. Published online 2022. https://www.ncbi.nlm.nih.gov/books/NBK470313/
  40. Kang, J.-S., & Lee, M.H. Overview of Therapeutic Drug Monitoring. Korean J Intern Med. 2009;24(1):1-5. doi:https://doi.org/10.3904/kjim.2009.24.1.1
  41. Mullokandov E, Ahn J, Szalkiewicz A. Protein Binding Drug-Drug Interaction between Warfarin and Tizoxanide in Human Plasma. 2014;2(7):7-9.
  42. Limdi, N. A., Limdi, M. A., Cavallari, L., Anderson, A. M., Crowley, M. R., Baird, M. F., Allon, M., & Beasley, T. M. Warfarin Dosing in Patients With Impaired Kidney Function. Am J Kidney Dis. 2010;56(6):823-831. doi:https://doi.org/10.1053/j.ajkd.2010.05.023
  43. Qamar, A., Vaduganathan, M., Greenberger, N. J., & Giugliano, R. P. Oral Anticoagulation in Patients With Liver Disease. J Am Coll Cardiol. 2018;71(19):2162-2175. doi:https://doi.org/10.1016/j.jacc.2018.03.023
  44. Agustini, T. T., Arifin, H., & Hanif AM. Perbandingan Dosis Warfarin terhadap Durasi Tercapainya Target INR pada Pasien CHF dengan Fibrilasi Atrial. J Sains Farm Klin. 2016;2(2):162-167. doi:https://doi.org/10.29208/jsfk.2016.2.2.67
  45. Kearon, C., Kahn, S. R., Agnelli, G., Goldhaber, S., Raskob, G. E., & Comerota AJ. Antithrombotic Therapy for Venous Thromboembolic Disease. Chest. 2008;133(6):454S-545S. doi:https://doi.org/10.1378/chest.08-0658
  46. Mueller, J. A., Patel, T., Halawa, A., Dumitrascu, A., & Dawson NL. Warfarin Dosing and Body Mass Index. Ann Pharmacother. 2014;48(5):584-588. doi:https://doi.org/10.1177/1060028013517541
  47. Drugs.com. Drug Interaction Checker. Drugs.com. Published 2023. Accessed November 3, 2023. https://www.drugs.com/interactions-check.php?drug_list=883-0,2311-0
  48. Ho, L. L., & Brighton, T. Warfarin, antiplatelet drugs and their interactions. Aust Prescr. 2002;25(4):81-85. doi:https://doi.org/10.18773/austprescr.2002.073
  49. Crader, M. F., Johns, T., & Arnold JK. Warfarin Drug Interactions. StatPearls Publishing.
  50. Dean L. Warfarin Therapy and VKORC1 and CYP Genotype. Medical Genetics Summaries.



DOI: https://doi.org/10.22146/jmpf.89898

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