Varfarin Tedavisi Alan Serebrovasküler Hastalığı Olan Hastalarda Terapötik Aralıkta Olma Oranlarının Değerlendirilmesi

Abstract

Amaç: Varfarin tedavisinin etkinliği, Terapötik Aralıkta Olma Zamanı (TTR) ile doğrudan ilişkilidir. Bu çalışmada, inme polikliniğinde izlenen warfarin kullanan hastalarda etkinlik ve hedefe ulaşma oranlarının belirlenmesi amaçlanmıştır.Yöntem: İnme polikliniğinde izlenen, varfarin kullanan 103 hasta, retrospektif olarak değerlendirildi. Varfarin kullanım süreleri, ve endikasyonlarıyla trombotik veya hemorajik komplikasyonları kaydedildi. Hedef INR değeri mekanik kapaklı hastalarda 3.0-3.5, diğer endikasyonlar için 2.0-3.0 arasında belirlendi.Bulgular: Çalışmaya 47’si erkek 56’sı kadın olmak üzere, ortalama yaşları 67.14 ± 14.19 olan 103 hasta dahil edildi.Varfarin kullanım endikasyonları sırasıyla hastaların %61,6’sında non-valvular atrial fibrilasyon, %12.62’sinde eko kardiyografide (EKO) akinetik/hipokinetik alan, %8.74’ünde trombofili, %3.88’inde metalik protez kapak, %6.79’unda sık geçici iskemik ataklar, %5.82’sinde atrial fibrilasyonla birlikte EKO’da hipokinetik alan ve % 0.87’sinde vertebral arter diseksiyonuydu. Hastaların %46.8’inin iyi kontrolde olduğu, ortalama TTR’nin %64.09 olduğu saptandı; ayrıca, TTR %36.8’inde %100 idi. İkisinde intraserebral kanama olan 10 hastada (%9.70) minör/majör hemorajik olay kaydedildi.Sonuç: Bu çalışmada saptanan ortalama TTR değeri, ülkemizde bildirilen orandan oldukça yüksektir. Çalışma bulgularımız, yakın izlemin inmeli hastalarda çok önemli ve hayati olduğunu göstermektedir. Varfarin kullanan inme hastalarının düzenli takibinin ve hastaları bilgilendirmenin optimal antikoagülasyon sağlanmasına ve komplikasyonları önlemeye yardımcı olacağına kanısındayız.

Keywords

• Varfarin
• Etkinlik
• Antikoagulasyon
• İskemik Serebrovasküler Hastalık

Evaluation of Time in Therapeutic Range in Patients with Cerebrovascular Disease Receiving Treatment with Warfarin

Abstract

Objective: The efficacy of warfarin therapy correlates with the Time in Therapeutic Range (TTR). This study aimed to investigate the efficacy and target achievement rates in patients using warfarin who were followed up in stroke outpatient clinics.Methods: In this study, 103 patients who had been under warfarin treatment were retrospectively evaluated. Duration and indications for warfarin use, thrombotic or hemorrhagic complications were recorded. Target INR value was 3.0-3.5 in patients with mechanical valves and 2.0-3.0 in those using warfarin for other indications.Results: In this study, 103 patients with a mean age of 67.14±14.19, 47 men and 56 women, were included. Indications for warfarin use, respectively, were non-valvular atrial fibrillation (AF) in 61.6% of the patients, akinetic/hypokinetic segment on echocardiography (ECHO) in 12.62%, thrombophilia in 8.74%, metallic prosthetic valve in 3.88%, frequent transient ischemic attacks in 6.79%, a hypokinetic segment on ECHO with atrial fibrillation in 5.82% and vertebral artery dissection in 0.87%. 46.8% of the patients were determined to be in good control, with a mean TTR of 64.09%; also, TTR was 100% in 36.8% of them. Minor/major hemorrhagic event was noted in 10 patients (9.70%), two of whom had an intracerebral hemorrhage.Conclusion: The mean TTR value detected in this study is considerably higher than the rate reported in our country. Findings of this study suggest that close monitoring is paramount of importance and vital in patients with stroke. Regular monitoring of stroke patients using warfarin will be beneficial in terms of informing patients, providing optimal anticoagulation and preventing complications.

Keywords

• Warfarin
• Ishemic Cerebrovascular Disease
• Anticogulation
• Efficacy
• Efficacy

References

1. Sacco RL, Adams R, Albers G, et al.; AHA; American Stroke Association Council on Stroke; Council on Cardiovascular Radiology and Intervention; American Academy of Neurology. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack. Stroke. 2006;37(2):577-617. https://doi.org/10.1161/01.STR.0000199147.30016.74.
2. Palacio S, Hart RG. Neurologic manifestations of cardiogenic embolism: an update. Neurol Clin. 2002;20(1):179-193, vii. https://doi.org/10.1016/s0733-8619(03)00058-6.
3. Schievink WI, Mokri B, O’Fallon WM. Recurrent spontaneous cervical-artery dissection. N Engl J Med. 1994;330(6):393-397. https://doi.org/10.1056/NEJM199402103300604.
4. Kasner SE. CADISS: a feasibility trial that answered its question. Lancet Neurol. 2015;14(4):342-343. https://doi.org/10.1016/S1474-4422(14)70271-6.
5. Ferro JM, Canhão P, Bousser MG, et al; ISCVT Investigators. Cerebral vein and dural sinus thrombosis in elderly patients. Stroke. 2005;36(9):1927-1932. https://doi.org/10.1161/01.STR.0000177894.05495.54.
6. Ferro JM, Canhão P, Stam J, et al; ISCVT Investigators. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke. 2004;35(3):664-670. https://doi.org/10.1161/01.STR.0000117571.76197.26.
7. Natarajan S, Ponde CK, Rajani RM, et al. Effect of CYP2C9 and VKORC1 genetic variations on warfarin dose requirements in Indian patients. Pharmacol Rep. 2013;65(5):1375-1382. https://doi.org/10.1016/s1734-1140(13)71496-8.
8. Joffe HV, Xu R, Johnson FB, et al. Warfarin dosing and cytochrome P450 2C9 polymorphisms. Thromb Haemost. 2004;91(6):1123-1128. https://doi.org/10.1160/TH04-02-0083.

9. Holbrook AM, Pereira JA, Labiris R, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005;165(10):1095-1106. https://doi.org/10.1001/archinte.165.10.1095.
10. Ansell J, Hirsh J, Hylek E, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6):160S-198S. https://doi.org/10.1378/chest.08-0670. P
11. Caldeira D, Cruz I, Morgado G, et al. Evaluation of time in therapeutic range in anticoagulated patients: a single-center, retrospective, observational study. BMC Res Notes. 2014;7:891. https://doi.org/10.1186/1756-0500-7-891.
12. Odén A, Fahlén M, Hart RG. Optimal INR for prevention of stroke and death in atrial fibrillation: a critical appraisal. Thromb Res. 2006;117(5):493-499. https://doi.org/10.1016/j.thromres.2004.11.025.
13. Rosendaal FR, Cannegieter SC, van der Meer FJ, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost. 1993;69(3):236-9.
14. Adams HP Jr, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke;24(1):35-41. https://doi.org/10.1161/01.str.24.1.35.
15. Farsad BF, Abbasinazari M, Dabagh A, Bakshandeh H. Evaluation of Time in Therapeutic Range (TTR) in Patients with Non-Valvular Atrial Fibrillation Receiving Treatment with Warfarin in Tehran, Iran: A Cross-Sectional Study. J Clin Diagn Res. 2016;10(9):FC04-FC06. https://doi.org/10.7860/JCDR/2016/21955.8457.
16. Schmitt L, Speckman J, Ansell J. Quality assessment of anticoagulation dose management: comparative evaluation of measures of time-in-therapeutic range. J Thromb Thrombolysis. 2003;15(3):213-216. https://doi.org/10.1023/B:THRO.0000011377.78585.63.
17. Singer DE, Hellkamp AS, Piccini JP, et al; ROCKET AF Investigators. Impact of global geographic region on time in therapeutic range on warfarin anticoagulant therapy: data from the ROCKET AF clinical trial. J Am Heart Assoc. 2013;2(1):e000067. https://doi.org/10.1161/JAHA.112.000067.
18. Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 15;365(11):981-992. https://doi.org/10.1056/NEJMoa1107039.
19. Cotté FE, Benhaddi H, Duprat-Lomon I, et al. Vitamin K antagonist treatment in patients with atrial fibrillation and time in therapeutic range in four European countries. Clin Ther. 2014;36(9):1160-1168. https://doi.org/10.1016/j.clinthera.2014.07.016.
20. Çelik A, İzci S, Kobat MA, et al; WARFARIN-TR Study Collaborates. The awareness, efficacy, safety, and time in therapeutic range of warfarin in the Turkish population: WARFARIN-TR. Anatol J Cardiol. 2016;16(8):595-600. https://doi.org/10.5152/AnatolJCardiol.2015.6474.
21. Kılıç S, Çelik A, Çakmak HA, et al. The Time in Therapeutic Range and Bleeding Complications of Warfarin in Different Geographic Regions of Turkey: A Subgroup Analysis of WARFARIN-TR Study. Balkan Med J. 2017;34(4):349-355. https://doi.org/10.4274/balkanmedj.2016.1617.
22. Pengo V, Pegoraro C, Cucchini U, Iliceto S. Worldwide management of oral anticoagulant therapy: the ISAM study. J Thromb Thrombolysis. 2006;21(1):73-77. https://doi.org/10.1007/s11239-006-5580-y.
23. Ertaş F, Kaya H, Kaya Z, et al. Epidemiology of atrial fibrillation in Turkey: preliminary results of the multicenter AFTER study. Turk Kardiyol Dern Ars. 2013;41(2):99-104. https://doi.org/10.5543/tkda.2013.18488.
24. Karaçağlar E, Atar I, Yetiş B, et al. Atriyal fibrilasyon hastalarında emboli risk faktörleri sıklığı ve emboli önleyici tedavilerin uygunluğunun araştırılması: Tek üçüncül bir merkez deneyimi. Anadolu Kardiyol Derg. 2012;12(5):384-90. https://doi.org/10.5152/akd.2012.123.
25. Wan Y, Heneghan C, Perera R, et al. Anticoagulation control and prediction of adverse events in patients with atrial fibrillation: a systematic review. Circ Cardiovasc Qual Outcomes. 2008 ;1(2):84-91. https://doi.org/10.1161/CIRCOUTCOMES.108.796185.
26. Connolly SJ, Pogue J, Eikelboom J, et al; ACTIVE W Investigators. Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation. 2008;118(20):2029-2037. https://doi.org/10.1161/CIRCULATIONAHA.107.750000