Keamanan Penggunaan Antiglukolan pada Pasien Rawat Inap Stroke Iskemik dengan Atrial Fibrilasi

https://doi.org/10.22146/jmpf.74893

Juniarto Mende(1), Fita Rahmawati(2*), Ika Puspitasari(3)

(1) Magister Farmasi Klinik, Fakultas Farmasi, Universitas Gadjah Mada
(2) Departemen Farmakologi dan Farmasi Klinik, Fakultas Farmasi, Universitas Gadjah Mada
(3) Departemen Farmakologi dan Farmasi Klinik, Fakultas Farmasi, Universitas Gadjah Mada
(*) Corresponding Author

Abstract


Atrial fibrillation can cause stroke due to blood stasis in the left atrium which triggers thrombus formation and embolization of the brain. Administration of anticoagulants is used to prevent clot formation to prevent the occurrence of stroke, but on the other hand, it is associated with the risk of bleeding side effects. This study aims to evaluate the safety of anticoagulants in ischemic stroke patients with atrial fibrillation. The study used a cross-sectional design. Retrospective data were taken from the medical records of RSUP Dr. Sardjito, Yogyakarta period January 2018 to December 2020. The research subjects were ischemic stroke patients with atrial fibrillation. Evaluation of the safety of anticoagulants includes the number of major and minor bleeding events in each type of anticoagulant and the factors that influence the occurrence of bleeding. A total of 70 patients met the study inclusion criteria. Bleeding occurred in 41 cases (58,57%). Major bleeding was 28 patients (40%) and minor bleeding was 13 patients (18,57%). The most common anticoagulant that causes bleeding is warfarin. Multivariate test of the factors that influence the occurrence of bleeding in kidney failure (OR = 5,990; 95% Cl 2,002-17,920; p = 0,001). Monitoring the side effects of anticoagulants, especially warfarin is necessary. Pharmacists can play an important role in monitoring and preventing bleeding events by taking into account risk factors, especially kidney failure.


Keywords


antikoagulan; atrial fibrilasi; pendarahan; stroke iskemik

Full Text:

PDF


References

  1. WHO [World Health Organization]. The Top 10 Causes of Death. Published online 2018. https://www.who.int/en/news-room/fact-sheets/detail/the-top-10-causes-of-death
  2. WHO [World Health Organization]. Indonesia: WHO Statistical Profile. Published online 2012.
  3. Kuriakose D, Xiao Z. Pathophysiology and Treatment of Stroke: Present Status and Future Perspectives. Int J Mol Sci. 2020;21(20):7609. doi:10.3390/ijms21207609
  4. Spence JD. Cardioembolic stroke: everything has changed. Stroke Vasc Neurol. 2018;3(2):76-83. doi:10.1136/svn-2018-000143
  5. Ball J. Which anticoagulant for stroke prevention in atrial fibrillation? BMJ. Published online November 28, 2017:j5399. doi:10.1136/bmj.j5399
  6. Kjerpeseth LJ, Selmer R, Ariansen I, Karlstad Ø, Ellekjær H, Skovlund E. Comparative effectiveness of warfarin, dabigatran, rivaroxaban and apixaban in non-valvular atrial fibrillation: A nationwide pharmacoepidemiological study. Garcia de Frutos P, ed. PLOS ONE. 2019;14(8):e0221500. doi:10.1371/journal.pone.0221500
  7. Wang C, Wu VC, Huang Y, et al. Safety and Effectiveness of Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Patients With Atrial Fibrillation and Anemia: A Retrospective Cohort Study. J Am Heart Assoc. 2019;8(9). doi:10.1161/JAHA.119.012029
  8. Paciaroni M, Agnelli G, Falocci N, et al. Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non–Vitamin‐K Oral Anticoagulants (RAF‐NOACs) Study. J Am Heart Assoc. 2017;6(12):e007034. doi:10.1161/JAHA.117.007034
  9. Senoo K, Lane D, Lip GY. Stroke and Bleeding Risk in Atrial Fibrillation. Korean Circ J. 2014;44(5):281. doi:10.4070/kcj.2014.44.5.281
  10. Piel-Julian ML, Mahévas M, Germain J, et al. Risk factors for bleeding, including platelet count threshold, in newly diagnosed immune thrombocytopenia adults. J Thromb Haemost. 2018;16(9):1830-1842. doi:10.1111/jth.14227
  11. Hamidon BB, Raymond AA. The Risk Factors of Gastrointestinal Bleeding in Acute Ischaemic Stroke. Med J Malays. 2006;61(3):5.
  12. Lemeshow S. Adequacy of Sample Size in Health Studies. (World Health Organization, ed.). Published on behalf of the World Health Organization by Wiley; 1990.
  13. Well G, Coyle D, Cameron C, et al. Safety, Effectiveness, and Cost Effectiveness of New Oral Anticoagulants Compared with Warfarin in Preventing Stroke and Other Cardiovascular Events in Patients with Atrial Fibrillation. Can Collab Drug Saf Eff Netw Meta-Anal. Published online 2012.
  14. Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients: Definitions of major bleeding in clinical studies. J Thromb Haemost. 2005;3(4):692-694. doi:10.1111/j.1538-7836.2005.01204.x
  15. Kim TH, Yang PS, Yu HT, et al. Age Threshold for Ischemic Stroke Risk in Atrial Fibrillation: Cohort Data Covering the Entire Korean Population. Stroke. 2018;49(8):1872-1879. doi:10.1161/STROKEAHA.118.021047
  16. Roy-O’Reilly M, McCullough LD. Age and Sex Are Critical Factors in Ischemic Stroke Pathology. Endocrinology. 2018;159(8):3120-3131. doi:10.1210/en.2018-00465
  17. Basu E, Salehi Omran S, Kamel H, Parikh NS. Sex differences in the risk of recurrent ischemic stroke after ischemic stroke and transient ischemic attack. Eur Stroke J. 2021;6(4):367-373. doi:10.1177/23969873211058568
  18. MacWalter RS, Wong SYS, Wong KYK, et al. Does Renal Dysfunction Predict Mortality After Acute Stroke?: A 7-Year Follow-Up Study. Stroke. 2002;33(6):1630-1635. doi:10.1161/01.STR.0000016344.49819.F7
  19. Son MK, Lim NK, Kim HW, Park HY. Risk of ischemic stroke after atrial fibrillation diagnosis: A national sample cohort. Bishopric NH, ed. PLOS ONE. 2017;12(6):e0179687. doi:10.1371/journal.pone.0179687
  20. Verdecchia P, Angeli F, Reboldi G. Hypertension and Atrial Fibrillation. Am Heart Assoc. 2018;122:17. doi:10.1161/CIRCRESAHA.117.311402
  21. Chen J, Li S, Zheng K, et al. Impact of Smoking Status on Stroke Recurrence. J Am Heart Assoc. 2019;8(8). doi:10.1161/JAHA.118.011696
  22. Qian Y, Ye D, Wu DJ, et al. Role of cigarette smoking in the development of ischemic stroke and its subtypes: a Mendelian randomization study. Clin Epidemiol. 2019;Volume 11:725-731. doi:10.2147/CLEP.S215933
  23. WHO. Tobacco & Stroke. World Health Organ. Published online 2016.
  24. Markidan J, Cole JW, Cronin CA, et al. Smoking and Risk of Ischemic Stroke in Young Men. Stroke. 2018;49(5):1276-1278. doi:10.1161/STROKEAHA.117.018859
  25. Dong J, Wang F, Sundararajan S. Use of Dual Antiplatelet Therapy Following Ischemic Stroke. Stroke. 2020;51(5). doi:10.1161/STROKEAHA.119.028400
  26. So CH, Eckman MH. Combined aspirin and anticoagulant therapy in patients with atrial fibrillation. J Thromb Thrombolysis. 2017;43(1):7-17. doi:10.1007/s11239-016-1425-5
  27. Chan Y, See L, Tu H, et al. Efficacy and Safety of Apixaban, Dabigatran, Rivaroxaban, and Warfarin in Asians With Nonvalvular Atrial Fibrillation. J Am Heart Assoc. 2018;7(8):e008150. doi:10.1161/JAHA.117.008150
  28. Liu F, Xu Z, Luo J, et al. Effectiveness and Safety of DOACs vs. VKAs in AF Patients With Cancer: Evidence From Randomized Clinical Trials and Observational Studies. Front Cardiovasc Med. 2021;8:766377. doi:10.3389/fcvm.2021.766377
  29. Connolly SJ, Ezekowitz MD, Yusuf S, Reilly PA, Wallentin L. Newly Identified Events in the RE-LY Trial. N Engl J Med. 2010;363(19):1875-1876. doi:10.1056/NEJMc1007378
  30. Uchino K. Dabigatran Association With Higher Risk of Acute Coronary Events: Meta-analysis of Noninferiority Randomized Controlled Trials. Arch Intern Med. 2012;172(5):397. doi:10.1001/archinternmed.2011.1666
  31. Tsai CT, Liao JN, Chiang CE, et al. Association of Ischemic Stroke, Major Bleeding, and Other Adverse Events With Warfarin Use vs Non–vitamin K Antagonist Oral Anticoagulant Use in Patients With Atrial Fibrillation With a History of Intracranial Hemorrhage. :11.
  32. Okumura K, Akao M, Yoshida T, et al. Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation. N Engl J Med. 2020;383(18):1735-1745. doi:10.1056/NEJMoa2012883
  33. Amin A. Oral anticoagulation to reduce risk of stroke in patients with atrial fibrillation: current and future therapies. Clin Interv Aging. Published online January 2013:75. doi:10.2147/CIA.S37818
  34. Yasaka M, Minematsu K, Toyoda K, et al. Rivaroxaban administration after acute ischemic stroke: The RELAXED study. :18.
  35. Frisullo G, Profice P, Brunetti V, et al. Prospective Observational Study of Safety of Early Treatment with Edoxaban in Patients with Ischemic Stroke and Atrial Fibrillation (SATES Study). Published online 2021:8.
  36. Tokunaga K, Yasaka M, Toyoda K, et al. Bridging Therapy With Heparin Before Starting Rivaroxaban in Ischemic Stroke or Transient Ischemic Attack With Non-Valvular Atrial Fibrillation. Circ J. 2022;86(6):958-963. doi:10.1253/circj.CJ-21-0617
  37. Chamorro A, Vila N, Ascaso C, Blanc R. Heparin in Acute Stroke With Atrial Fibrillation: Clinical Relevance of Very Early Treatment. Arch Neurol. 1999;56(9):1098. doi:10.1001/archneur.56.9.1098
  38. Freedman KB, Brookenthal KR, Fitzgerald RH, Williams S, Lonner JH. A Meta-Analysis of Thromboembolic Prophylaxis Following Elective Total Hip Arthroplasty*. JBJS. 2000;82(7):929.
  39. Mismetti P, Quenet S, Levine M, et al. Enoxaparin in the Treatment of Deep Vein Thrombosis With or Without Pulmonary Embolism. Chest. 2005;128(4):2203-2210. doi:10.1378/chest.128.4.2203
  40. Hylek EM, Held C, Alexander JH, et al. Major Bleeding in Patients With Atrial Fibrillation Receiving Apixaban or Warfarin. J Am Coll Cardiol. 2014;63(20):2141-2147. doi:10.1016/j.jacc.2014.02.549
  41. Feiz F, Sedghi R, Salehi A, Hatam N, Bahmei J, Borhani-Haghighi A. Study of the Efficacy, Safety and Tolerability of Low-Molecular-Weight Heparin vs. Unfractionated Heparin as Bridging Therapy in Patients with Embolic Stroke due to Atrial Fibrillation. J Vasc Interv Neurol. 2016;9(1):7.
  42. Paciaroni M, Agnelli G, Micheli S, Caso V. Efficacy and Safety of Anticoagulant Treatment in Acute Cardioembolic Stroke: A Meta-Analysis of Randomized Controlled Trials. Stroke. 2007;38(2):423-430. doi:10.1161/01.STR.0000254600.92975.1f
  43. Warden BA, Diep C, Ran R, Thomas M, Cigarroa JE. The effect of heparin infusion intensity on outcomes for bridging hospitalized patients with atrial fibrillation. Clin Cardiol. 2019;42(10):995-1002. doi:10.1002/clc.23256
  44. Manoukian SV, Feit F, Mehran R, et al. Impact of Major Bleeding on 30-Day Mortality and Clinical Outcomes in Patients With Acute Coronary Syndromes. J Am Coll Cardiol. 2007;49(12):1362-1368. doi:10.1016/j.jacc.2007.02.027
  45. Baser O, Du J, Xie L, Baser E. PCV35 COMPARISON OF MAJOR BLEEDING RELATED MORTALITY, HEALTH CARE UTILIZATION AND COSTS OF PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION. Value Health. 2011;14(3):A38. doi:10.1016/j.jval.2011.02.223
  46. Ogata T, Kamouchi M, Matsuo R, et al. Gastrointestinal Bleeding in Acute Ischemic Stroke: Recent Trends from the Fukuoka Stroke Registry. Cerebrovasc Dis Extra. 2014;4(2):156-164. doi:10.1159/000365245
  47. Sedaghat M, Lima BS, Bouzari R, Shadlou S. Gastrointestinal Bleeding Associated With Warfarin and Rivaroxaban Therapy in Atrial Fibrillation Cases with Concomitant Coagulopathy. Cardiovasc Hematol Disord Drug Targets. 2021;21(2):123-127. doi:10.2174/1871529X20999201231210044
  48. Kirchhof P, Haas S, Amarenco P, et al. Impact of Modifiable Bleeding Risk Factors on Major Bleeding in Patients With Atrial Fibrillation Anticoagulated With Rivaroxaban. J Am Heart Assoc. 2020;9(5):e009530. doi:10.1161/JAHA.118.009530
  49. Esteve-Pastor MA, Rivera-Caravaca JM, Lip GY. Hypertension and Atrial Fibrillation: Balancing Stroke and Bleeding Risks. Am J Hypertens. 2017;30(11):1063-1065. doi:10.1093/ajh/hpx135
  50. Kodani E, Atarashi H, Inoue H, et al. Impact of Blood Pressure Control on Thromboembolism and Major Hemorrhage in Patients With Nonvalvular Atrial Fibrillation: A Subanalysis of the J‐RHYTHM Registry. J Am Heart Assoc. 2016;5(9):e004075. doi:10.1161/JAHA.116.004075
  51. Ishii M, Ogawa H, Unoki T, et al. Relationship of Hypertension and Systolic Blood Pressure With the Risk of Stroke or Bleeding in Patients With Atrial Fibrillation: The Fushimi AF Registry. Am J Hypertens. 2017;30(11):1073-1082. doi:10.1093/ajh/hpx094
  52. Ndrepepa G, Groha P, Lahmann AL, et al. Increased bleeding risk during percutaneous coronary interventions by arterial hypertension: Bleeding and Arterial Hypertension. Catheter Cardiovasc Interv. 2016;88(2):184-190. doi:10.1002/ccd.26272
  53. Rahmadina A, Gofir A, Nugroho AE. The Role of Anticoagulation Control on the Mortality Rate in Warfarin Treated Ischemic Stroke Patients with Atrial Fibrillation. 2015;7(4):5.
  54. Dahal K, Kunwar S, Rijal J, Schulman P, Lee J. Stroke, Major Bleeding, and Mortality Outcomes in Warfarin Users With Atrial Fibrillation and Chronic Kidney Disease. Chest. 2016;149(4):951-959. doi:10.1378/chest.15-1719
  55. Ocak G, Rookmaaker MB, Algra A, et al. Chronic kidney disease and bleeding risk in patients at high cardiovascular risk: a cohort study. J Thromb Haemost. 2018;16(1):65-73. doi:10.1111/jth.13904
  56. Jun M, James MT, Manns BJ, et al. The association between kidney function and major bleeding in older adults with atrial fibrillation starting warfarin treatment: population based observational study. BMJ. 2015;350(feb03 4):h246-h246. doi:10.1136/bmj.h246
  57. Lip GYH, Clementy N, Pericart L, Banerjee A, Fauchier L. Stroke and Major Bleeding Risk in Elderly Patients Aged ≥75 Years With Atrial Fibrillation: The Loire Valley Atrial Fibrillation Project. Stroke. 2015;46(1):143-150. doi:10.1161/STROKEAHA.114.007199
  58. Liabeuf S, Scaltieux LM, Masmoudi K, et al. Risk Factors for Bleeding in Hospitalized at Risk Patients With an INR of 5 or More Treated With Vitamin K Antagonists. Medicine (Baltimore). 2015;94(52):e2366. doi:10.1097/MD.0000000000002366
  59. Gulilat M, Jandoc R, Jeyakumar N, et al. Association of Sex With Stroke and Bleeding Risk of Apixaban and Rivaroxaban in Elderly Atrial Fibrillation Patients Using Propensity Score Weights. CJC Open. 2022;4(1):56-64. doi:10.1016/j.cjco.2021.09.002
  60. Pol T, Held C, Westerbergh J, et al. Dyslipidemia and Risk of Cardiovascular Events in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Therapy: Insights From the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) Trial. J Am Heart Assoc. 2018;7(3):e007444. doi:10.1161/JAHA.117.007444
  61. Hasegawa S, Okada A, Aso S, et al. Association Between Diabetes and Major Bleeding Complications of Renal Biopsy. Kidney Int Rep. 2022;7(2):232-240. doi:10.1016/j.ekir.2021.11.013
  62. Osório J. Aspirin and diabetes mellitus—no increase in bleeding risk? Nat Rev Endocrinol. 2012;8(8):442-442. doi:10.1038/nrendo.2012.108
  63. Mentias A, Briasoulis A, Shantha G, Alvarez P, Vaughan-Sarrazin M. Impact of Heart Failure Type on Thromboembolic and Bleeding Risk in Patients With Atrial Fibrillation on Oral Anticoagulation. Am J Cardiol. 2019;123(10):1649-1653. doi:10.1016/j.amjcard.2019.02.027
  64. Apostolakis S, Lane DA, Guo Y, Buller H, Lip GYH. Performance of the HEMORR2HAGES, ATRIA, and HAS-BLED Bleeding Risk–Prediction Scores in Patients With Atrial Fibrillation Undergoing Anticoagulation. J Am Coll Cardiol. 2012;60(9):861-867. doi:10.1016/j.jacc.2012.06.019
  65. Langsted A, Nordestgaard B. Smoking is Associated with Increased Risk of Major Bleeding: A Prospective Cohort Study. Thromb Haemost. 2019;119(01):039-047. doi:10.1055/s-0038-1675798
  66. Toyoda K, Yasaka M, Iwade K, et al. Dual Antithrombotic Therapy Increases Severe Bleeding Events in Patients With Stroke and Cardiovascular Disease: A Prospective, Multicenter, Observational Study. Stroke. 2008;39(6):1740-1745. doi:10.1161/STROKEAHA.107.504993
  67. Gami AS. Anticoagulant plus antiplatelet treatment increased the risk of bleeding in atrial fibrillation. Evid Based Med. 2005;10(2):56-56. doi:10.1136/ebm.10.2.56
  68. Ray WA, Chung CP, Murray KT, et al. Association of Oral Anticoagulants and Proton Pump Inhibitor Cotherapy With Hospitalization for Upper Gastrointestinal Tract Bleeding. JAMA. 2018;320(21):2221. doi:10.1001/jama.2018.17242
  69. Mizokami Y, Yamamoto T, Atarashi H, et al. Current status of proton pump inhibitor use in Japanese elderly patients with non-valvular atrial fibrillation: A subanalysis of the ANAFIE Registry. Ai T, ed. PLOS ONE. 2020;15(11):e0240859. doi:10.1371/journal.pone.0240859
  70. Lin KJ, Hernández S, Rodríguez LAG. Acid Suppressants Reduce Risk of Gastrointestinal Bleeding in Patients on Antithrombotic or Anti-Inflammatory Therapy. 2011;141(1):9.



DOI: https://doi.org/10.22146/jmpf.74893

Article Metrics

Abstract views : 2085 | views : 2280

Refbacks

  • There are currently no refbacks.


Copyright (c) 2022 JURNAL MANAJEMEN DAN PELAYANAN FARMASI (Journal of Management and Pharmacy Practice)

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

©Jurnal Manajemen dan Pelayanan Farmasi
Faculty of Pharmacy
Universitas Gadjah Mada
Creative Commons License
View My Stats