Challenges in Achieving Optimal Warfarin Anticoagulation Control: A Comprehensive Exploration and Proposed Holistic Approaches
In Indonesia warfarin remains the most widely oral anticoagulation prescribed. However, the time in therapeutic range remain low in Indonesia and also in some countries in throughout the world. This study aimed to analyse the challenges of optimal warfarin control from the perspectives of healthcare professionals, patients, health system, and to propose strategies to address these challenges. This research consists of two stages. The first stage was a prospective observational study aiming to analyse the challenges and the second stage of the research was focus group discussion to propose strategies to overcome the challenges. The result of this study showed that the average of TTR was 49.4 ± 32.1, where only 37.5% patients had TTR ≥ 65%. The average dosing consistency obtained was 62.33 ± 32.42%. With regard to INR monitoring interval, almost all patient who had supraterapeutic INR had their INR monitoring interval set to 1 month after the dose adjustment. There were also identified that only 43.8% patients classified as adherent and only 39.5 % patients had good knowledge of warfarin, indicating that the level of medication adherence and knowledge was not optimal. In this study, 14.6% of patients received other drugs that potentially interacted with warfarin that cause fluctuate INR. In conclusion, this study's results showed that there were multiple challenges for optimal warfarin control including barrier for dosing consistency, INR monitoring, patients’ adherence and knowledge, as well as drug interactions. However, there will be still room for improvement. The proposed strategy that likely will achieve optimal benefit was a holistic approach that combine multifaceted strategies to address each barrier.
Ageno, W., Gallus, A. S., Wittkowsky, A., Crowther, M., Hylek, E. M., & Palareti, G. (2012). Oral Anticoagulant Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest, 141(2), e44S-e88S. https://doi.org/10.1378/CHEST.11-2292.
Akbar, Mohammad Rizki, Mega Febrianora, and Mohammad Iqbal. (2022). Warfarin Usage in Patients With Atrial Fibrillation Undergoing Hemodialysis in Indonesian Population. Current Problems in Cardiology 48(5): 101104. https://doi.org/10.1016/j.cpcardiol.2022.101104.
Al-Saikhan, F. I., Ashour, R., Abd-Elaziz, M. A., Ashour, R. H., & Langaee, T. (2018). Anticoagulation therapy: Patients attitude, knowledge, and concerns regarding their effects on the international normalized ratio (INR) in Saudi Arabia Properties and substrates of glutathione transferase zeta 1 View project New anti-bilharzial treatment View project Anticoagulation therapy: patients attitude, knowledge, and concerns regarding their effects on the international normalized ratio (INR) in Saudi Arabia. Biomedical Research (India), 29(7). https://doi.org/10.4066/biomedicalresearch.29-17-2761.
Balkhi, B., Al-Rasheedi, M., Elbur, A. I., & Alghamadi, A. (2018). Association between satisfaction with and adherence to warfarin therapy on the control of international normalized ratio: A hospital-based study in Saudi Arabia. Saudi Pharmaceutical Journal, 26(1), 145–149.https://doi.org/10.1016/J.JSPS.2017.11.010.
Bhat, Manzoor et al. (2020). “Efficacy of Point-of-Care for INR Testing Compared to Standard Laboratory Methods at a Tertiary Care Hospital in Saudi Arabia.” (June).
Chen, S.-Y., Wu, N., Gulseth, M., LaMori, J., Bookhart, B. K., Boulanger, L., Fields, L., & Schein, J. (2013). One-Year Adherence to Warfarin Treatment for Venous Thromboembolism in High-Risk Patients and Its Association with Long-term Risk of Recurrent Events. JMCP Journal of Managed Care Pharmacy, 19(4). https://doi.org/https://doi.org/10.18553/jmcp.2013.19.4.291
Clarkesmith, Danielle E, Helen M Pattison, Gregory Y H Lip, and Deirdre A Lane. (2013). “Educational Intervention Improves Anticoagulation Control in Atrial Fibrillation Patients : The TREAT Randomised Trial.” 8(9): 1–10.
Dimberg, Ivar et al. (2012). European Journal of Internal Medicine Computerised Assistance for Warfarin Dosage — Effects on Treatment Quality. European Journal of Internal Medicine 23(8): 742–44. http://dx.doi.org/10.1016/j.ejim.2012.07.011.
Hanssens, Y., & Kheir, N. (2010). Evaluation of patients’ knowledge on warfarin in outpatient anticoagulation clinics in a teaching hospital in Qatar. Saudi Medical Journal, 31(6), 672–677.
Holm, J., Lindh, J.D., Anderson, M.L. Mannheimer, B., (2017). The Effect Of Amiodaron On Warfarin Anticoagulation; A Register-Based Nationwide Cohort Study Involving The Swedish Population. J Thromb Haemost. 15;446-453
January, C. T., Wann, L. S., Alpert, J. S., Calkins, H., Cigarroa, J. E., Cleveland, J. C., Conti, J. B., Ellinor, P. T., Ezekowitz, M. D., Field, M. E., Murray, K. T., Sacco, R. L., Stevenson, W. G., Tchou, P. J., Tracy, C. M., & Yancy, C. W. (2014). 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Journal of the American College of Cardiology, 64(21), e1–e76. https://doi.org/10.1016/J.JACC.2014.03.022.
Kavousi, M. (2020). Differences in Epidemiology and Risk Factors for Atrial Fibrillation Between Women and Men. Frontiers in Cardiovascular Medicine, 7(3). https://doi.org/10.3389/FCVM.2020.00003/BIBTEX
Kim, Y. K., Nieuwlaat, R., Connolly, S. J., Schulman, S., Meijer, K., Raju, N., Kaatz, S., & Eikelboom, J. W. (2010). Effect of a simple two-step warfarin dosing algorithm on anticoagulant control as measured by time in therapeutic range: a pilot study. Journal of Thrombosis and Haemostasis, 8(1), 101–106. https://doi.org/10.1111/J.1538-7836.2009.03652.X.
Kripalani, S., Risser, J., Gatti, M. E., & Jacobson, T. A. (2009). Development and Evaluation of the Adherence to Refills and Medications Scale (ARMS) among Low-Literacy Patients with Chronic Disease. Value in Health, 12(1), 118–123. https://doi.org/10.1111/J.1524-4733.2008.00400.X.
Lane, M., Zeringue, A.& McDonald, J., (2014). Serious Bleeding Events Due To Warfarin And Antibiotic Co-Prescription In A Cohort Of Veterans. Amerincan Journal Medicine, 127(7),pp 657-663
Li, X., Sun, S., Wang, Q., Chen, B., Zhao, Z., & Xu, X. (2018). Assessment of patients’ warfarin knowledge and anticoagulation control at a joint physician- and pharmacist-managed clinic in China. Patient Preference and Adherence, 12, 783. https://doi.org/10.2147/PPA.S156734.
Lip, G. Y. H., Banerjee, A., Boriani, G., Chiang, C. en, Fargo, R., Freedman, B., Lane, D. A., Ruff, C. T., Turakhia, M., Werring, D., Patel, S., & Moores, L. (2018). Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report. Chest, 154(5), 1121–1201. https://doi.org/10.1016/j.chest.2018.07.040.
Magnussen, C., Niiranen, T. J., Ojeda, F. M., Gianfagna, F., Blankenberg, S., Njølstad, I., Vartiainen, E., Sans, S., Pasterkamp, G., Hughes, M., Costanzo, S., Donati, M. B., Jousilahti, P., Linneberg, A., Palosaari, T., de Gaetano, G., Bobak, M., den Ruijter, H. M., Mathiesen, E., … Schnabel, R. B. (2017). Sex differences and similarities in atrial fibrillation epidemiology, risk factors, and mortality in community cohorts: Results from the biomarcare consortium (Biomarker for cardiovascular risk assessment in Europe). Circulation, 136(17), 1588–1597. https://doi.org/10.1161/CIR-CULATIONAHA.117.028981
Matalqah, L. M., Radaideh, K. M., Sulaiman, S. A. S., Hassali, M. A., & Kader, M. A. S. A. (2013). Relationship between patients’ warfarin knowledge and anticoagulation control: results of a validated tool in Malaysia. Affiliation. J Pharm Biomed Sci, 30(30), 967–974.
Minister of Health of Indonesia. (2021). Keputusan Menteri Kesehatan Republik Indonesia Nomor HK.01.07/MENKES/6485/2021 Tentang Formularium Nasional. Kmk No. Hk.01.07-menkes-6485-2021 Ttg Formularium Nasional [nl2z4zwwy2l8] (doku.pub)
Nishimura, R. A., Otto, C. M., Bonow, R. O., Carabello, B. A., Erwin, J. P., Fleisher, L. A., Jneid, H., Mack, M. J., McLeod, C. J., O’Gara, P. T., Rigolin, V. H., Sundt, T. M., & Thompson, A. (2017). 2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology, 70(2), 252–289. https://doi.org/10.1016/J.JACC.2017.03.011
Noor A, Khan MA, Warsi A, et al. (2021). Evaluation of a pharmacist vs. haematologist-managed anticoagulation clinic: A retrospective cohort study. Saudi Pharmaceutical Journal, 29(10),1173–1180. DOI:10.1016/J.JSPS.2021.08.015.
Putriana, Norisca Aliza, Keri Lestari, Melisa Intan Barliana, and Sri Hartini. (2017). “Effects of Pharmacist Counseling on Compliance and International Normalized Ratio Score on Outpatients Receiving Warfarin at Dr. Hasan Sadikin Bandung Hospital West Java, Indonesia.” Asian Journal of Pharmaceutical and Clinical Research 10(Special Issue May): 72–75.
Rahmatini, Rahmatini et al. (2020). “Plasma Warfarin Level and International Normalized Ratio Do Not Correlate with Bleeding Events in Indonesian Patients of Minangkabau Ethnicity with Atrial Fibrillation.” Open Access Macedonian Journal of Medical Sciences 8(B): 192–97.
Rose, A. J., Hylek, E. M., Berlowitz, D. R., Ash, A. S., Reisman, J. I., & Ozonoff, A. (2011). Prompt repeat testing after out-of-range inr values a quality indicator for anticoagulation care. Circulation: Cardiovascular Quality and Outcomes, 4(3), 276–282. https://doi.org/10.1161/CIRCOUTCOMES.110.960096.
Rosendaal, F. R., Cannegieter, S. C., van der Meer, F. J. M., & Briet, E. (1993). A method to determine the optimal intensity of oral anticoagulant therapy. Thrombosis and Haemostasis, 69(3), 236–239. https://doi.org/10.1055/S-0038-1651587/ID/OR_8.
Sanoski, C. A., Bauman, J. L., (2002). Clinical Observations with The Amiodaron/Warfarin Interaction. Chest 121(1);19-23
Sekarsari DD, Ardhianto P, Kresnoadi E, et al. (2021). Time in therapeutic range (ttr) in atrial fibrillation with warfarin therapy in Semarang, Indonesia. Jurnal Kedokteran Diponegoro (Diponegoro Medical Journal) [Online], Oct;10(5):315-319. DOI:10.14710/dmj.v10i5.30046
Sevilla-Cazes, J., Finkleman, B. S., Chen, J., Brensinger, C. M., Epstein, A. E., Streiff, M. B., & Kimmel, S. E. (2017). Association Between Patient-Reported Medication Adherence and Anticoagulation Control. The American Journal of Medicine, 130(9), 1092-1098.e2. https://doi.org/10.1016/J.AMJMED.2017.03.038.
Singer, D. E., Hellkamp, A. S., Piccini, J. P., Mahaffey, K. W., Lokhnygina, Y., Pan, G., Halperin, J. L., Becker, R. C., Breithardt, G., Hankey, G. J., Hacke, W., Nessel, C. C., Patel, M. R., Califf, R. M., Fox, K. A. A., & ROCKET AF Investigators. (2013). Impact of global geographic region on time in therapeutic range on warfarin anticoagulant therapy: data from the ROCKET AF clinical trial. Journal of the American Heart Association, 2(1). https://doi.org/10.1161/JAHA.112.000067.
Smith, M. B., Christensen, N., Wang, S., Strohecker, J., Day, J. D., Weiss, J. P., Crandall, B. G., Osborn, J. S., Anderson, J. L., Horne, B. D., Muhlestein, J. B., Lappe, D. L., Moss, H., Oliver, J., Viau, K., & Bunch, T. J. (2010). Warfarin Knowledge in Patients with Atrial Fibrillation: Implications for Safety, Efficacy, and Education Strategies. Cardiology, 116(1), 61–69. https://doi.org/10.1159/000314936.
The Joint Commission. (2017). Ambulatory health care 2018 national patient safety goals. Retrieved from https://www.jointcommission.org/assets/1/6/NPSG_Chapter_AHC_Jan2018.pdf.
U.S. Department of Health and Human Services, Office of Disease Promotion and Prevention. (2014). National action plan for adverse drug event prevention. Retrieved from https://health.gov/hcq/pdfs/ade-action-plan-508c.pdf.
van Damme, S., van Deyk, K., Budts, W., Verhamme, P., & Moons, P. (2011). Patient knowledge of and adherence to oral anticoagulation therapy after mechanical heart-valve replacement for congenital or acquired valve defects. Heart & Lung, 40(2), 139–146. https://doi.org/10.1016/J.HRTLNG.2009.11.005.
van Spall, H. G. C., Wallentin, L., Yusuf, S., Eikelboom, J. W., Nieuwlaat, R., Yang, S., Kabali, C., Reilly, P. A., Ezekowitz, M. D., & Connolly, S. J. (2012). Variation in warfarin dose adjustment practice is responsible for differences in the quality of anticoagulation control between centers and countries: An analysis of patients receiving warfarin in the randomized evaluation of long-term anticoagulation therapy (RE-LY) trial. Circulation, 126(19), 2309–2316. https://doi.org/10.1161/CIRCULATIONAHA.112.101808.
Vazquez, Sara R.a; Fleming, Ryan P.a; Johnson, Stacy A.b. Comparison of two point-of-care international normalized ratio devices and laboratory method. Blood Coagulation & Fibrinolysis 28(7):p 534-539, October 2017. | DOI: 10.1097/MBC.0000000000000633
Wang N, Qiu S, Yang Y, et al. (2021). Physician–pharmacist collaborative clinic model to improve anticoagulation quality in atrial fibrillation patients receiving warfarin: an analysis of time in therapeutic range and a nomogram development. Frontiers in Pharmacology, 12(673302). DOI: 10.3389/fphar.2021.673302.
Wang, Y., Kong, M. C., Lee, L. H., Ng, H. J., & Ko, Y. (2014). Knowledge, satisfaction, and concerns regarding warfarin therapy and their association with warfarin adherence and anticoagulation control. Thrombosis Research, 133(4), 550–554. https:/doi.org/10.1016/J.THROMRES.2014.01.002.
Wilson, A. S., Vazquez, S. R., Saunders, J. A., & Witt, D. M. (2022). Concordance of experienced-based maintenance warfarin dosing vs. algorithm-based dosing. Thrombosis Update, 6, 100093. https://doi.org/10.1016/j.tru.2021.100093.
Woller, Scott C et al. (2015). Computerized Clinical Decision Support Improves Warfarin Management and Decreases Recurrent Venous Thromboembolism.
Zhao, S., Zhao, H., Wang, X., Gao, C., Qin, Y., Cai, H., Chen, B., & Cao, J. (2017). Factors influencing medication knowledge and beliefs on warfarin adherence among patients with atrial fibrillation in China. Patient Preference and Adherence, 11, 213–220. https://doi.org/10.2147/PPA.S120962.