Study on warfarin dose adjustment strategy at different stages after mechanical valve replacement of mitral valve_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

CHEN Li ^1,2 , CHEN Sai ¹ , LI Tao ¹ , ZHAO Tingting ^1,2 , TONG Qi ¹ ,  QIAN Yongjun ¹

1. Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, 610041, P.R.China;
2. West China School of Nursing, Sichuan University, Chengdu, 610041, P.R.China;

Corresponding author：

QIAN Yongjun, Email: qianyongjun@scu.edu.cn

Keywords：

Warfarin; mechanical valve replacement of mitral valve; anticoagulant therapy; international normalized ratio; time in therapeutic range; fraction of time in therapeutic range

DOI：

10.7507/1007-4848.202105053

Video：

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Objective To explore the anticoagulant strategy of adjusting the dose of warfarin at different stages after mechanical valve replacement of mitral valve.Methods Clinical data of a total of 302 patients, including 76 males and 226 females, with an average age of 50.1±10.1 years, who underwent mechanical mitral valve replacement in the Chinese adult cardiac surgery database from 2013 to 2017 were retrospectively analyzed. According to the dose adjustment strategy of taking warfarin, the patients were divided into a D group (adjusting warfarin dose in days) and a W group (adjusting warfarin dose in weeks) to evaluate the anti-coagulation effect of warfarin.Results The total follow-up time was 423277 d (1159.7 years). There was no significant difference in the overall anticoagulant strength, and the warfarin dose adjusted in days was better in the early postoperative period (P<0.05), especially in patients over 60 years. It was better to adjust warfarin dose in weeks in the middle and long periods (P<0.05), especially in patients ≤40 years. In terms of the stability of anticoagulation, it was better to adjust the dosage of warfarin in weeks (P<0.05). It was better to adjust the dosage of warfarin in weeks for early, middle- and long-term anticoagulant therapy after operation (P<0.05), especially in the females aged >40 and ≤50 years.Conclusion Within the target range of international normalized ratio (1.5-2.5), the anticoagulant strategy of adjusting warfarin dose in days after mechanical valve replacement of mitral valve can achieve a better anticoagulant strength, and adjusting the dosage of warfarin in weeks is better in the middle- and long-term after operation. In general, the anticoagulant effect is more stable in the short term when warfarin dose is adjusted on a weekly basis.

Citation： CHEN Li, CHEN Sai, LI Tao, ZHAO Tingting, TONG Qi, QIAN Yongjun. Study on warfarin dose adjustment strategy at different stages after mechanical valve replacement of mitral valve. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2021, 28(8): 945-953. doi: 10.7507/1007-4848.202105053 Copy

1.	Oh EM, Lee OS, Jang BM, et al. Effect of post-operative anticoagulation management in patients who have undergone On-X mechanical heart valve replacement surgery on post-discharge warfarin therapy. J Clin Pharm Ther, 2020, 45(4): 767-773.
2.	Yan H, Yin JY, Zhang W, et al. Possible strategies to make warfarin dosing algorithm prediction more accurately in patients with extreme dose. Clin Pharmacol Ther, 2018, 103(2): 184.
3.	Witt DM, Clark NP, Kaatz S, et al. Guidance for the practical management of warfarin therapy in the treatment of venous thromboembolism. J Thromb Thrombolysis, 2016, 41(1): 187-205.
4.	Ho KM, Bham E, Pavey W. Incidence of venous thromboembolism and benefits and risks of thromboprophylaxis after cardiac surgery: A systematic review and meta-analysis. J Am Heart Assoc, 2015, 4(10): e002652.
5.	Zhang F, Huang J, He RJ, et al. Herb-drug interaction between Styrax and warfarin: Molecular basis and mechanism. Phytomedicine, 2020, 77: 153287.
6.	Gemmati D, Burini F, Talarico A, et al. The active metabolite of warfarin (3'-Hydroxywarfarin) and correlation with INR, warfarin and drug weekly dosage in patients under oral anticoagulant therapy: A pharmacogenetics study. PLoS One, 2016, 11(9): e0162084.
7.	Yu HY, Lin MH, Lin LY, et al. Do patients with high CHA 2 DS 2-VASc scores need high intensity of anticoagulants after valve surgery? Circ J, 2018, 82(4): 1186-1194.
8.	Kose E, Arai S, An T, et al. Analysis of factors affecting time in therapeutic range control after warfarin administration. Pharmazie, 2015, 70(7): 494-498.
9.	Kodani E, Atarashi H, Inoue H, et al. Target intensity of anticoagulation with warfarin in Japanese patients with valvular atrial fibrillation–subanalysis of the J-RHYTHM Registry. Circ J, 2015, 79(2): 325-330.
10.	Siddiqui S, DeRemer CE, Waller JL, et al. Variabilityfarin. J Innov Card Rhythm Manag, 2018, 9(12): 3428-3434.
11.	Pokorney SD, Simon DN, Thomas L, et al. Patients' time in therapeutic range on warfarin among US patients with atrial fibrillation: Results from ORBIT-AF Registry. Am Heart J, 2015, 170(1): 141-148.
12.	Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J, 2016, 37(38): 2893-2962.
13.	Yu HY, Tsai HE, Chen YS, et al. Comparison of warfarin dosage fluctuation with time in therapeutic range for bleeding or thromboembolism rate in Chinese patients. J Formos Med Assoc, 2019, 118(2): 611-618.
14.	Fenta TG, Assefa T, Alemayehu B. Quality of anticoagulation management with warfarin among outpatients in a tertiary hospital in Addis Ababa, Ethiopia: A retrospective cross-sectional study. BMC Health Serv Res, 2017, 17(1): 389.
15.	Grzymala-Lubanski B, Labaf A, Englund E, et al. Mechanical heart valve prosthesis and warfarin-treatment quality and prognosis. Thromb Res, 2014, 133(5): 795-798.
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.
17.	任荣, 钱永军, 黄云, 等. 机械瓣膜置换术后稳定期华法林抗凝治疗质量评价及其基因学研究. 中国胸心血管外科临床杂志, 2019, 26(7): 681-687.
18.	Hao Y, Yang J, Zheng X, et al. Chinese patients with heart valve replacement do not benefit from warfarin pharmacogenetic testing on anticoagulation outcomes. Ther Drug Monit, 2019, 41(6): 748-754.
19.	Horstkotte D, Schulte H, Bircks W, et al. Unexpected findings concerning thromboembolic complications and anticoagulation after complete 10 year follow up of patients with St. Jude Medical prostheses. J Heart Valve Dis, 1993, 2(3): 291-301.

1. Oh EM, Lee OS, Jang BM, et al. Effect of post-operative anticoagulation management in patients who have undergone On-X mechanical heart valve replacement surgery on post-discharge warfarin therapy. J Clin Pharm Ther, 2020, 45(4): 767-773.
2. Yan H, Yin JY, Zhang W, et al. Possible strategies to make warfarin dosing algorithm prediction more accurately in patients with extreme dose. Clin Pharmacol Ther, 2018, 103(2): 184.
3. Witt DM, Clark NP, Kaatz S, et al. Guidance for the practical management of warfarin therapy in the treatment of venous thromboembolism. J Thromb Thrombolysis, 2016, 41(1): 187-205.
4. Ho KM, Bham E, Pavey W. Incidence of venous thromboembolism and benefits and risks of thromboprophylaxis after cardiac surgery: A systematic review and meta-analysis. J Am Heart Assoc, 2015, 4(10): e002652.
5. Zhang F, Huang J, He RJ, et al. Herb-drug interaction between Styrax and warfarin: Molecular basis and mechanism. Phytomedicine, 2020, 77: 153287.
6. Gemmati D, Burini F, Talarico A, et al. The active metabolite of warfarin (3'-Hydroxywarfarin) and correlation with INR, warfarin and drug weekly dosage in patients under oral anticoagulant therapy: A pharmacogenetics study. PLoS One, 2016, 11(9): e0162084.
7. Yu HY, Lin MH, Lin LY, et al. Do patients with high CHA 2 DS 2-VASc scores need high intensity of anticoagulants after valve surgery? Circ J, 2018, 82(4): 1186-1194.
8. Kose E, Arai S, An T, et al. Analysis of factors affecting time in therapeutic range control after warfarin administration. Pharmazie, 2015, 70(7): 494-498.
9. Kodani E, Atarashi H, Inoue H, et al. Target intensity of anticoagulation with warfarin in Japanese patients with valvular atrial fibrillation–subanalysis of the J-RHYTHM Registry. Circ J, 2015, 79(2): 325-330.
10. Siddiqui S, DeRemer CE, Waller JL, et al. Variabilityfarin. J Innov Card Rhythm Manag, 2018, 9(12): 3428-3434.
11. Pokorney SD, Simon DN, Thomas L, et al. Patients' time in therapeutic range on warfarin among US patients with atrial fibrillation: Results from ORBIT-AF Registry. Am Heart J, 2015, 170(1): 141-148.
12. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J, 2016, 37(38): 2893-2962.
13. Yu HY, Tsai HE, Chen YS, et al. Comparison of warfarin dosage fluctuation with time in therapeutic range for bleeding or thromboembolism rate in Chinese patients. J Formos Med Assoc, 2019, 118(2): 611-618.
14. Fenta TG, Assefa T, Alemayehu B. Quality of anticoagulation management with warfarin among outpatients in a tertiary hospital in Addis Ababa, Ethiopia: A retrospective cross-sectional study. BMC Health Serv Res, 2017, 17(1): 389.
15. Grzymala-Lubanski B, Labaf A, Englund E, et al. Mechanical heart valve prosthesis and warfarin-treatment quality and prognosis. Thromb Res, 2014, 133(5): 795-798.
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.
17. 任荣, 钱永军, 黄云, 等. 机械瓣膜置换术后稳定期华法林抗凝治疗质量评价及其基因学研究. 中国胸心血管外科临床杂志, 2019, 26(7): 681-687.
18. Hao Y, Yang J, Zheng X, et al. Chinese patients with heart valve replacement do not benefit from warfarin pharmacogenetic testing on anticoagulation outcomes. Ther Drug Monit, 2019, 41(6): 748-754.
19. Horstkotte D, Schulte H, Bircks W, et al. Unexpected findings concerning thromboembolic complications and anticoagulation after complete 10 year follow up of patients with St. Jude Medical prostheses. J Heart Valve Dis, 1993, 2(3): 291-301.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Study on warfarin dose adjustment strategy at different stages after mechanical valve replacement of mitral valve

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