Warfarin kullanma zamanı metalik protez kapak hastalarında terapötik aralıktaki INR değer süresini etkiler mi?

Abstract

Amaç : K vitamin antagonisti olan Varfarin metalik kalp kapaklı hastalarda onaylanmış oral antikoagulan tedavidir. Etkin antikoagulan tedaviyi sürdürmeyi zorlayan birçok faktör nedeniyle bu hastaların sık aralıklarla INR takibine alınması önerilmektedir.Bu çalışmanın amacı varfarin kullanma zamanının antikoagulasyona etkisi olup olmadığını araştırmaktır. Materyal ve metod: Metalik protez kapaklı toplam 60 hasta çalışmaya dahil edildi. Tüm hastalara ilk ayda varfarini saat 19:30 -20:00 arasında, ikinci ayda saat 09:30 ve 10:00 arasında alması söylendi.Hastalardan takip süresinde 15 günde bir INR ölçümü yapıldı.Birinci ve ikinci ay terapötik aralıktaki zaman yüzdesi (TTR) değerleri (sırasıyla birinci ve ikinci TTR) Rosendaal metoduyla hesaplandı. Sonuçlar:Ortalama yaş 59.6 ± 9.6 yıldı.%36,7'si (n:22) erkekti.Birinci ve ikinci TTR değerleri arasında anlamlı fark bulunmadı (66.23 ± 40.7% vs 64.12 ± 41.13%, p=0.783).Birinci aydaki ortalama INR değeri ikin aydakinden anlamlı olarak daha düşüktü (2.73 ± 0.53 vs 3.06 ± 0.47, p=0.001). Karar:Çalışma sonuçları varfarin kullanma periyodunun etkin antikoagulasyon sağlanan toplam zamana bir etkisi olmadığını göstermiştir. Bunun birlikte sabah varfarin kullanımı daha yüksek INR değerlerine neden olmaktadır.

Keywords

• warfarin
• Uluslararası normalleştirilmiş oran
• farmakokinetik

DOES THE TIMING OF WARFARIN INGESTION AFFECT THE TIME IN THERAPEUTIC RANGE IN PATIENTS WITH METALLIC PROSTHETIC VALVE?

Abstract

Aim: Warfarin , a vitamin K antagonist, is the only approved oral agent to provide anticoagulation in patients with metallic prosthetic valves. Since effectively initiating and maintaining anticoagulation is challenging due to various factors , those patients undergo frequent periodic INR testing. The aim of this study was to investigate the effect of the timing of warfarin ingestion on the stability of anticoagulation. Materials and Methods: A total of 60 patients with metallic prosthetic valves were included in the study. First, all the patients were informed to take warfarin between 19:30 and 20:00 during the first month, then to take warfarin between 09:30 and 10:00 during the second month. All the patients underwent INR monitoring once every 15 days during the follow-up period. The time in therapeutic range (TTR) values for the first month and second month ( referred to as ‘first TTR’ and ‘second TTR’, respectively) were calculated separately using the Rosendaal method. Results: The mean age ( ± SD) of the patients was 59.6 ± 9.6 years and 36.7% (n=22) were male. There was no significant difference between the first TTR and second TTR values of the patients (66.23 ± 40.7% vs 64.12 ± 41.13%, p=0.783). The mean INR value in the first month was found to be significantly lower than in the second month (2.73 ± 0.53 vs 3.06 ± 0.47, p=0.001). Conclusion:.The study results showed that the timing of warfarin ingestion did not affect the stability of anticoagulation although taking the warfarin in the morning provided higher INR values.

Keywords

• warfarin
• international normalized ratio
• pharmacokinetic

References

1. 1. Nelson WW, Choi JC, Vanderpoel J, et al. Impact of co-morbidities and patient characteristics on international normalized ratio control over time in patient with nonvalvular atrial fibrillation. Am J Cardiol. 2013;112:509–12.
2. 2. Rose AJ, Hylek EM, Ozonoff A, et al.Patient characteristics associated with oral anticoagulation control: results of the Veterans AffaiRs Study to Improve Anticoagulation (VARIA) J Thromb Haemost. 2010;8:2182–91.
3. 3. Costa GL, Lamego RM, Colosimo EA,et al. Identifying potential predictors of high-quality oral anticoagulation assessed by time in therapeutic international normalized ratio range: a prospective, long-term, single-center, observational study. Clin Ther. 2012;34:1511–20.
4. 4. Mearns ES, White CM, Kohn CG, et al.Quality of vitamin K antagonist control and outcomes in atrial fibrillation patients: a meta-analysis and meta-regression. Thromb J. 2014;12:14
5. 5. Apostolakis S, Sullivan RM, Olshansky B, et al.Factors affecting quality of anticoagulation control among patients with atrial fibrillation on warfarin: the SAMe-TT2R2 score. Chest. 2013;144:1555–63.
6. 6. Havers-Borgersen E, Butt JH, Vinding NE, Torp-Pedersen C,et al. Time in therapeutic range and risk of thromboembolism and bleeding in patients with a mechanical heart valve prosthesis. J Thorac Cardiovasc Surg. 2020 ;159(1):74-83.
7. 7. Bonow RO, Carabello BA, Chatterjee K et al. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2008 Oct 7;118(15):e523-661.
8. 8. Gallego P, Vilchez JA, Lane DA. Apixaban compared with warfarin for stroke prevention in atrial fibrillation: implications of time in therapeutic range. Circulation. 2013;127:2163–65

9. 9. Farsad FB,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 Sep; 10(9): FC04–FC06.
10. 10. Schmitt L, Speckman J, Ansell J. Quality assessment of anticoagulation dose management: comparative evaluation of measures of time-in-therapeutic range. Journal of Thrombosis and Thrombolysis. 2003;15:213–16.
11. 11. Rosendaal F, Cannegieter S, Van der Meer F, et al.A method to determine the optimal intensity of oral anticoagulant therapy. Thrombosis and haemostasis 1993;69:236-9.
12. 12. Tan CSY, Fong AYY, Jong YH, et al. INR Control of Patients with Mechanical Heart Valve on Long-Term Warfarin Therapy. Glob Heart. 2018 Dec;13(4):241-4.)
13. 13. Boonyawat K, Wang L, Lazo-Langner A, et al. The effect of low-dose oral vitamin K supplementation on INR stability in patients receiving warfarin. A randomised trial. Thromb Haemost. 2016 Aug ;116(3):480-5.
14. 14. Garrison SR, Green L, Kolber MR, et al. The Effect of Warfarin Administration Time on Anticoagulation Stability (INRange): A Pragmatic Randomized Controlled Trial. The Annals of Family Medicine 2020;18:42-9.
15. 15. Demirbağ R, Sade LE, Aydın M, et al. The Turkish registry of heart valve disease. Turk Kardiyol Dern Ars. 2013 Jan;41(1):1-10
16. 16. Ozer S, Hallioglu O, Ozkutlu S, et al.Childhood acute rheumatic fever in Ankara. Turk J Pediatr 2005 ;47:120–4
17. 17. Avarello I, Bianchi S, Toschi V, et al.Time in therapeutic range is lower in women than in men and is not explained by differences in age or comorbidity. Thromb Res. 2021 Jul;203:18-21
18. 18. Holford NH. Clinical pharmacokinetics and pharmacodynamics of warfarin. Understanding the dose-effect relationship. Clin Pharmacokinet. 1986 Nov-Dec;11(6):483-504.