Anticoagulation with warfarin in Patients from Eastern Colombia: A Prospective Longitudinal Observational Study
Abstract
Introduction. Warfarin, an oral anticoagulant with a narrow therapeutic margin, exposes patients to risks associated with its therapy, underscoring the need for constant monitoring. In this context, this study evaluated the therapeutic follow-up of warfarin in anticoagulated patients at an ambulatory healthcare institution in eastern Colombia. Methodology. An observational analytical longitudinal study with prospective follow-up was conducted, including 244 patients, in which sociodemographic and clinical variables obtained from medical records were analyzed over a one-year period. Results. Within the participant cohort, 53.7% were female, and the prevailing diagnosis was atrial fibrillation and atrial flutter (46.3%). Generic warfarin was administered to 60.7% of participants, while 52.9% were concurrently prescribed an average of 5 medications. Alterations in weekly therapeutic dose showed significant correlation with time within therapeutic range (p = 0.000) and occurrence of adverse drug events (p = 0.001). Drug non-adherence (13.1%) emerged as the most frequent event. Assessment of 3,032 International Normalized Ratio results revealed a mean time in therapeutic range of 149 days, with an average of 6 tests falling within this range. Discussion. Suboptimal anticoagulation control was primarily associated with dose adjustments and patient non-adherence rather than manufacturer changes or comorbidities. These findings underscore the critical role of patient education in warfarin therapy management, particularly among elderly populations with polypharmacy. Conclusion. Anticoagulation programs should implement rigorous monitoring of weekly therapeutic dose administration, complemented by continuous education regarding timing of intake, posology, and factors influencing the International Normalized Ratio. This recommendation has particular significance given the advanced age of most patients.
References
1. Wendelboe A, Weitz JI. Global Health Burden of Venous Thromboembolism. Arterioscler Thromb Vasc Biol [Internet]. 2024;44(5):1007-1011. doi: https://doi.org/10.1161/atvbaha.124.320151
2. GBD 201 Forecasting Collaborators. Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021. Lancet [Internet]. 2024;403(10440):2204–2256. doi: https://doi.org/10.1016/S0140-6736(24)00685-8
3. Mandefro BT, Sundara SV, Lu X, Busmail H, Weerakoon S, Avula S, et al. Effectiveness and safety of direct oral anticoagulants versus warfarin in patients with mechanical heart valves: A systematic review. Cureus [Internet]. 2025;17(8):e89736. doi: https://doi.org/10.7759/cureus.89736
4. Leviner DB, Abraham D, Ronai T, Sharoni E. Mechanical Valves: Past, Present, and Future-A review. J Clin Med [Internet]. 2024;13(13):3768. doi: https://doi.org/10.3390/jcm13133768
5. Lampropoulos K, Penteris M, Gerotziafas G. Direct oral anticoagulants in valvular diseases and prosthetic valves: Why not? Cardiovasc Drugs Ther [Internet]. 2025. doi: https://doi.org/10.1007/s10557-025-07736-8
6. Campbell HA, Link KP. Studies on the hemorrhagic sweet clover disease: IV. The isolation and crystallization of the hemorrhagic agent. J Biol Chem [Internet]. 1941;138(1):21–33. Available from: https://www.sciencedirect.com/science/article/pii/S0021925818514071
7. Colombia, Ministerio de Salud y Protección Social. Resolución 2765 de 2025, por la cual se actualizan los servicios y tecnologías de salud financiados con recursos de la Unidad de Pago por Capitación (UPC). Available from: https://consultorsalud.com/wp-content/uploads/2025/12/Resolucion-No-2765-de-2025.pdf
8. Kamthornthanakarn I, Krittayaphong R. Optimal INR level for warfarin therapy after mechanical mitral valve replacement. BMC Cardiovasc Disord [Internet]. 2019;19:97. doi: https://doi.org/10.1186/s12872-019-1078-3
9. Hurst K, Lee R, Handa A. Quick reference guide to the new oral anticoagulants. J Vasc Surg [Internet]. 2016;63(6):1653-1657. doi: https://doi.org/10.1016/j.jvs.2016.02.054
10. Di Fusco SA, Lucà F, Gulizia MM, Gabrielli D, Colivicchi F. Emerging clinical setting of direct oral anticoagulants: atherothrombotic events prevention. J Cardiovasc Med (Hagerstown) [Internet]. 2020;21(1):1–5. doi: https://doi.org/10.2459/jcm.0000000000000894
11. Falcone M, Martín MM, Romero-Sandoval N, Grupo GRAAL-WARF-GRAAL. Time in therapeutic range and incidence of warfarin complications in a 20-year retrospective cohort. Aten Primaria [Internet]. 2022;54(8). doi: https://doi.org/10.1016/j.aprim.2022.102410
12. Wańkowicz P, Staszewski J, Dębiec A, Nowakowska-Kotas M, Szylińska A, Rotter I. Ischemic stroke risk factors in patients with atrial fibrillation treated with new oral anticoagulants. J Clin Med [Internet]. 2021;10(6):1223. doi: https://doi.org/10.3390/jcm10061223
13. Mostbauer H, Nishkumay O, Rokyta O, Vavryniuk V. Warfarin resistance: possibilities to solve this problem. A case report. J Int Med Res [Internet]. 2022;50(6):3000605221103959. doi: https://doi.org/10.1177/03000605221103959
14. Ceresetto JM, Tajer C, Duboscq C, Bottaro F, Casais P, Korin J, et al. Recomendaciones de manejo de los anticoagulantes orales directos (DOACs) anti-Xa y anti-IIa. Medicina (B Aires) [Internet]. 2022;82(Supl 2):1–55. Available from: https://www.scielo.org.ar/scielo.php?script=sci_arttext&pid=S0025-76802022000300001
15. Nepal G, Kharel S, Bhagat R, Shing YK, Coghlan MA, Poudyal P, et al. Safety and efficacy of direct oral anticoagulants in cerebral venous thrombosis: A meta-analysis. Acta Neurol Scand [Internet]. 2022;145(1):10-23. doi: https://doi.org/10.1111/ane.13506
16. Kim S, Yun YM, Chae HJ, Cho HJ, Ji M, Kim IS, et al. Clinical pharmacogenetic testing and application: Laboratory medicine clinical practice guidelines. Ann Lab Med [Internet]. 2017;37(2):180-193. doi: https://doi.org/10.3343/alm.2017.37.2.180
17. Martínez-Sánchez LM, Urrego-Vásquez A, Gaviria-García JR, Ospina-Sánchez JP, Jaramillo-Jaramillo LI, Hernández-Restrepo F. Anticoagulación oral: un reto para el apego terapéutico. Med Int Méx [Internet]. 2022;38(2):355-365. Available from: https://www.medigraphic.com/pdfs/medintmex/mim-2022/mim222m.pdf
18. Afzal U, Lau J, Yap J, Fam JM, Ooi IJ, Anbalakan K, et al. Ultraslow thrombolysis of mechanical tricuspid prosthetic thrombosis. JACC Case Rep [Internet]. 2025;30(19):104211. doi: https://doi.org/10.1016/j.jaccas.2025.104211
19. Azzam H, Elwakeel H, Awad I, El-Farahaty R, El-Gilany AH, El-Sharawy S. VKORC1 and CYP2C9 genotypes in Egyptian patients with warfarin resistance. Blood Coagul Fibrinolysis [Internet]. 2016;27(2):121-126. doi: https://doi.org/10.1097/mbc.0000000000000168
20. Mostbauer H, Nishkumay O, Rokyta O, Vavryniuk V. Warfarin resistance: possibilities to solve this problem. A case report. J Int Med Res [Internet]. 2022;50(6):3000605221103959. doi: https://doi.org/10.1177/03000605221103959
21. Patel S, Singh R, Preuss CV, Patel N. Warfarin. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470313/
22. Douxfils J, Gosselin RC. Laboratory assessment of direct oral anticoagulants. Semin Thromb Hemost [Internet]. 2017;43(3):277-290. doi: https://doi.org/10.1055/s-0036-1597296
23. Naseralallah L, Nasrallah D, Koraysh S, Al-Qudimat AR. Real-world evaluation of the interaction between rifampicin and warfarin: a retrospective observational study. Adv Pharmacol Pharm Sci [Internet]. 2025;2025:5607280. doi: https://doi.org/10.1155/adpp/5607280
24. Vega AJ, Smith C, Matejowsky HG, Thornhill KJ, Borne GE, Mosieri CN, et al. Warfarin and antibiotics: drug interactions and clinical considerations. Life (Basel) [Internet]. 2023;13(8):1661. doi: https://doi.org/10.3390/life13081661
25. Dorgalaleh A, Favaloro EJ, Bahraini M, Rad F. Standardization of prothrombin time/international normalized ratio (PT/INR). Int J Lab Hematol. 2021 Feb;43(1):21–28. doi: 10.1111/ijlh.13349.
26. Demir N, Yucelen SY, Cetin EG, Kalkan KE, Ozturkmen YA, Demir E, et al. Determining INR awareness of the patients who use warfarin and rates of achieving the target dosage. Sisli Etfal Hastan Tip Bul [Internet]. 2020;54(3):357-363. doi: https://doi.org/10.14744/semb.2019.76993
27. Breeding E, Trainor M, Kabir I, Martyak M. Utility of thromboelastography in detecting NOAC-related coagulopathy in traumatic brain injury. J Surg Res [Internet]. 2023;283:423-427. doi: https://doi.org/10.1016/j.jss.2022.09.010
28. Chou CL, Hsu CC, Chou CY, Chen TJ, Chou LF, Chou YC. Tablet splitting of narrow therapeutic index drugs: a nationwide survey in Taiwan. Int J Clin Pharm [Internet]. 2015;37(6):1235-1241. doi: https://doi.org/10.1007/s11096-015-0194-0
29. Pinzón JF, Maldonado C, Díaz JA, Segura O. Costos directos e impacto sobre la morbimortalidad hospitalaria de eventos adversos prevenibles a medicamentos en una institución de tercer nivel de Bogotá. Biomedica [Internet]. 2011;31(3):307–315. doi: https://doi.org/10.7705/biomedica.v31i3.320
30. Ceballos M, González CA, Holguín HA, Amariles P. Relevancia clínica de la interacción de la warfarina y del acetaminofén: estudio de cohortes retrospectivo. Rev Colomb Cardiol [Internet]. 2016;23(5):351-360. doi: https://doi.org/10.1016/j.rccar.2015.10.009
31. Laverde LP, Gómez SE, Montenegro AC, Lineros A, Wills B, Buitrago AF. Experiencia de una clínica de anticoagulación. Rev Colomb Cardiol [Internet]. 2015;22(5):224-230. doi: https://doi.org/10.1016/j.rccar.2015.04.008
32. Rosendaal FR, Cannegieter SC, van der Meer FJM, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost [Internet]. 1993;69(3):236-239. Available from: https://pubmed.ncbi.nlm.nih.gov/8470047/
33. Miranda-Rosero HA, Osorio S, Giraldo-Méndez DP, Duque-Botero J, Cataño JU, Tobón LI, et al. Tiempo en rango terapéutico (TRT) en clínica de anticoagulación: Reportes de eventos adversos y factores asociados a bajo TRT. Acta Med Colomb [Internet]. 2016;41(1):42-48. doi: https://doi.org/10.36104/amc.2016.524
34. Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr [Internet]. 2017;17(1):1–10. doi: https://doi.org/10.1186/s12877-017-0621-2
35. Sirois C, Domingues NS, Laroche ML, Zongo A, Lunghi C, Guénette L, et al. Polypharmacy definitions for multimorbid older adults need stronger foundations to guide research, clinical practice and public health. Pharmacy (Basel) [Internet]. 2019;7(3):126. doi: https://doi.org/10.3390/pharmacy7030126
36. Colombia, Ministerio de Salud. Resolución 8430 de 1993, por la cual se establecen las normas científicas, técnicas y administrativas para la investigación en salud. Available from: https://www.minsalud.gov.co/sites/rid/lists/bibliotecadigital/ride/de/dij/resolucion-8430-de-1993.pdf
37. Colombia, Congreso de la República. Ley 23 de 1981, por la cual se dictan normas en materia de ética médica. Diario Oficial No. 35.711. Available from: https://www.alcaldiabogota.gov.co/sisjur/normas/Norma1.jsp?i=154130
38. Colombia, Ministerio de Salud. Resolución 1995 de 1999, por la cual se establecen normas para el manejo de la historia clínica. Available from: https://www.alcaldiabogota.gov.co/sisjur/normas/Norma1.jsp?i=16737
39. Colombia, Ministerio de Salud y Protección Social. Resolución 839 de 2017, por la cual se modifican la Resolución 1995 de 1999 y se dictan otras disposiciones. Available from: https://www.alcaldiabogota.gov.co/sisjur/normas/Norma1.jsp?i=16737 .
40. Colombia, Congreso de la República. Ley 1581 de 2012, por la cual se dictan disposiciones generales para la protección de datos personales. Available from: https://www.funcionpublica.gov.co/eva/gestornormativo/norma.php?i=49981
41. Kahlon P, Nabi S, Arshad A, Jabbar A, Haythem A. Warfarin dosing and time required to reach therapeutic international normalized ratio in patients with hypercoagulable conditions. Turk J Haematol [Internet]. 2016;33(4):299-303. doi: https://doi.org/10.4274/tjh.2015.0271
42. Ng SS, Nathisuwan S, Phrommintikul A, Chaiyakunapruk N. Cost-effectiveness of warfarin care bundles and novel oral anticoagulants for stroke prevention in patients with atrial fibrillation in Thailand. Thromb Res [Internet]. 2020;185:63-71. doi: https://doi.org/10.1016/j.thromres.2019.11.012
43. Wei H, Cui C, Cui X, Liu Y, Li D. Cost-effectiveness analysis of dabigatran, rivaroxaban and warfarin in the prevention of stroke in patients with atrial fibrillation in China. BMC Health Serv Res [Internet]. 2021;21(1):96. doi: https://doi.org/10.1186/s12913-021-06084-1
44. Abohelaika S, Kamali F, Avery P, Robinson B, Kesteven P, Wynne H. Anticoagulation control and cost of monitoring of older patients on chronic warfarin therapy in three settings in North East England. Age Ageing [Internet]. 2014;43(5):708-711. doi: https://doi.org/10.1093/ageing/afu074
45. Burnett A, Tiongson J, Downey R, Mahan CE. The hidden costs of anticoagulation in hospitalized patients with non-valvular atrial fibrillation. Expert Opin Pharmacother [Internet]. 2013;14(9):1119-1133. doi: https://doi.org/10.1517/14656566.2013.789022
46. Janzic A, Kos M. Cost effectiveness of novel oral anticoagulants for stroke prevention in atrial fibrillation depending on the quality of warfarin anticoagulation control. Pharmacoeconomics [Internet]. 2015;33(4):395–408. doi: https://doi.org/10.1007/s40273-014-0246-7
47. Fitzgerald P, Stancampiano F, Kurklinsky A, Nikpour N, McLeod E, Li Z, et al. Warfarin therapy in atrial fibrillation: assessment of patient knowledge of risks and benefits. J Community Hosp Intern Med Perspect [Internet]. 2020;10(3):179-187. doi: https://doi.org/10.1080/20009666.2020.1767270
48. BioMed Research International. Retracted: A cohort study on the safety and efficacy of warfarin and rivaroxaban in anticoagulant therapy in patients with atrial fibrillation study. Biomed Res Int [Internet]. 2023;2023:9756404. doi: https://doi.org/10.1155/2023/9756404
49. Okumura K, Komatsu T, Yamashita T, Okuyama Y, Harada M, Konta Y, et al. Time in the therapeutic range during warfarin therapy in Japanese patients with non-valvular atrial fibrillation: a multicenter study of its status and influential factors. Circ J [Internet]. 2011;75(9):2087-2094. doi: https://doi.org/10.1253/circj.cj-11-0350
50. Falamić S, Lucijanić M, Hadžiabdić MO, Marušić S, Bačić VV. Pharmacist’s interventions improve time in therapeutic range of elderly rural patients on warfarin therapy: a randomized trial. Int J Clin Pharm [Internet]. 2018;40(5):1078-1085. doi: https://doi.org/10.1007/s11096-018-0691-z
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