Analysis of factors for international normalized ratio levels>3.0 in patients undergoing warfarin anticoagulation therapy after mechanical heart valve replacement_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHAO Shengmin ^1,2 , FU Bo ³ , ZHANG Fengying ⁴ , MA Weijie ² , HUANG Shourui ⁵ , LI Qian ⁶ , TAO Huan ⁷ , DONG Li ¹ ,  CHEN Jin ^1,2

1. Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China;
2. Clinical Epidemiology and Evidence-based Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China;
3. Department of Cardiovascular Surgery, Tianjin Chest Hospital, Tianjin, 300222, P. R. China;
4. Hospital of Chengdu Office of People’s Government of Tibetan Autonomous Region, Chengdu, 610041, P. R. China;
5. West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, P. R. China;
6. Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China;
7. Department of Hematology and Research Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China;

Corresponding author：

CHEN Jin, Email: ebm_chenjin@126.com

Keywords：

Mechanical heart valve replacement; warfarin; anticoagulation therapy; international normalized ratio

DOI：

10.7507/1007-4848.202402023

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Objective To investigate the factors influencing international normalized ratio (INR)>3.0 in patients undergoing warfarin anticoagulation therapy after mechanical heart valve replacement. Methods A retrospective analysis was performed on the clinical data of patients who underwent mechanical heart valve replacement surgery and received warfarin anticoagulation therapy at West China Hospital of Sichuan University from January 1, 2011 to June 30, 2022. Based on the discharge INR values, patients were divided into two groups: an INR≤3.0 group and an INR>3.0 group. The factors associated with INR>3.0 at the time of discharge were analyzed. Results A total of 8901 patients were enrolled, including 3409 males and 5492 females, with a median age of 49.3 (43.5, 55.6) years. The gender, body mass index (BMI), New York Heart Association (NYHA) cardiac function grading, INR, glutamic oxaloacetic transaminase, and preoperative prothrombin time (PT) were statistically different between the two groups (P<0.05). Multivariate logistic regression analysis revealed that lower BMI, preoperative PT>15 s, and mitral valve replacement were independent risk factors for INR>3.0 at discharge (P<0.05). Conclusion BMI, preoperative PT, and surgical site are factors influencing INR>3.0 at discharge in patients undergoing warfarin anticoagulation therapy after mechanical heart valve replacement. Special attention should be given to patients with lower BMI, longer preoperative PT, and mitral valve replacement to avoid excessive anticoagulation therapy.

1.	高润霖. 中国心瓣膜病现状. 华西医学, 2018, 33(2): 127-131.Gao RL. Current status of valvular heart disease in China. West China Med J, 2018, 33(2): 127-131.
2.	Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: Executive summary: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation, 2021, 143(5): e35-e71.
3.	International Warfarin Pharmacogenetics Consortium, Klein TE, Altman RB, et al. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med, 2009, 360(8): 753-764.
4.	Bourgeois S, Jorgensen A, Zhang EJ, et al. A multi-factorial analysis of response to warfarin in a UK prospective cohort. Genome Med, 2016, 8(1): 2.
5.	Spina E, Barbieri MA, Cicala G, et al. Clinically relevant drug interactions between newer antidepressants and oral anticoagulants. Expert Opin Drug Metab Toxicol, 2020, 16(1): 31-44.
6.	Wang M, Zeraatkar D, Obeda M, et al. Drug-drug interactions with warfarin: A systematic review and meta-analysis. Br J Clin Pharmacol, 2021, 87(11): 4051-4100.
7.	Wysowski DK, Nourjah P, Swartz L. Bleeding complications with warfarin use: A prevalent adverse effect resulting in regulatory action. Arch Intern Med, 2007, 167(13): 1414-1419.
8.	Loebstein R, Yonath H, Peleg D, et al. Interindividual variability in sensitivity to warfarin: Nature or nurture? Clin Pharmacol Ther, 2001, 70(2): 159-164.
9.	中华医学会心血管病学分会, 中国老年学学会心脑血管病专业委员会. 华法林抗凝治疗的中国专家共识. 中华内科杂志, 2013, 52(1): 76-82.Chinese Society of Cardiology, Chinese Geriatrics Society. Chinese expert consensus on warfarin anticoagulation therapy. Chin J Intern Med, 2013, 52(1): 76-82.
10.	Cheng TO. Chinese patients require lower dosage of warfarin. Int J Cardiol, 2010, 139(1): 1.
11.	Zhou XM, Zhuang W, Hu JG, et al. Low-dose anticoagulation in Chinese patients with mechanical heart valves. Asian Cardiovasc Thorac Ann, 2005, 13(4): 341-344.
12.	Cheung YF, Leung MP. Low dose oral anticoagulation therapy in Chinese children with congenital heart disease. J Paediatr Child Health, 1998, 34(6): 563-567.
13.	中华医学会胸心血管外科分会瓣膜病外科学组. 心脏瓣膜外科抗凝治疗中国专家共识. 中华胸心血管外科杂志, 2022, 38(3): 164-174.The Group of Valve Surgery, Chinese Society for Thoracic and Cardiovascular Surgery. Consensus of Chinese experts on anticoagulant therapy in cardiac valve surgery. Chin J Thorac Cardiovasc Surg, 2022, 38(3): 164-174.
14.	洪珊珊, 严美华, 傅新阳, 等. 心脏瓣膜置换术后服用华法林致出血的危险因素分析. 中外医疗, 2022, 41(35): 54-58.Hong SS, Yan MH, Fu XY, et al. Risk factors of warfarin bleeding after heart valve replacement. Chin Foreign Med Res, 2022, 41(35): 54-58.
15.	张进华, 刘茂柏, 蔡铭智, 等. 模型引导的华法林精准用药: 中国专家共识(2022版). 中国临床药理学与治疗学, 2022, 27(11): 1201-1212.Zhang JH, Liu MB, Cai MZ, et al. Model informed precision dosing of warfarin: China expert consensus re-port (2022 version). Chin J Clin Pharmacol Ther, 2022, 27(11): 1201-1212.
16.	屈清荣, 凡中霞, 李颖颖, 等. 心脏机械瓣膜置换术后患者华法林抗凝并发症的发生率及其影响因素分析. 护士进修杂志, 2014, 29(6): 518-521.Qu QR, Fan ZX, Li YY, et al. Analysis of the incidence and influencing factors of warfarin anticoagulation complications in patients after mechanical heart valve replacement. J Nurses Train, 2014, 29(6): 518-521.
17.	贾晓英, 韩艳艳, 王晓锋. 心脏机械瓣膜置换术后华法林抗凝治疗效果及INR抗凝强度范围分析. 现代诊断与治疗, 2020, 31(12): 1918-1920.Jia XY, Han YY, Wang XF. Analysis of the efficacy of warfarin anticoagulation therapy and INR anticoagulation intensity range after mechanical heart valve replacement. Mod Diagn Treat, 2020, 31(12): 1918-1920.
18.	许建屏, 石应康, 董力, 等. 中国人心脏瓣膜置换术后低强度抗凝治疗3000例随访1年报告. 四川大学学报(医学版), 2016, 47(1): 90-92.Xu JP, Shi YK, Dong L, et al. Low intensity anticoagulation therapy for chinese population with heart valve replacement: 3 000 cases follow-up. J Sichuan Univ (Med Sci Ed), 2016, 47(1): 90-92.
19.	董力, 石应康, 许建屏, 等. 中国心脏瓣膜术后多中心低强度抗凝治疗注册登记及随访研究. 中华医学杂志, 2016, 96(19): 1489-1494.Dong L, Shi YK, Xu JP, et al. The multicenter study on the registration and follow-up of low anticoagulation therapy for the heart valve operation in China. Natl Med J China, 2016, 96(19): 1489-1494.
20.	Wei M, Ye F, Xie D, et al. A new algorithm to predict warfarin dose from polymorphisms of CYP4F2, CYP2C9 and VKORC1 and clinical variables: Derivation in Han Chinese patients with non valvular atrial fibrillation. Thromb Haemost, 2012, 107(6): 1083-1091.
21.	Wells PS, Majeed H, Kassem S, et al. A regression model to predict warfarin dose from clinical variables and polymorphisms in CYP2C9, CYP4F2, and VKORC1: Derivation in a sample with predominantly a history of venous thromboembolism. Thromb Res, 2010, 125(6): e259-e264.
22.	Tao Y, Chen YJ, Fu X, et al. Evolutionary ensemble learning algorithm to modeling of warfarin dose prediction for Chinese. IEEE J Biomed Health Inform, 2019, 23(1): 395-406.
23.	张春雨. PT、APTT、TT、Fg检测及临床应用. 中国实用医药, 2015, 10(7): 108-109.Zhang CY. Detection and clinical application of PT, APTT, TT, and Fg. China Pract Med, 2015, 10(7): 108-109.
24.	徐博, 刘金成, 俞世强, 等. 人工机械心脏瓣膜置换术后抗凝治疗强度与并发症发生率的关系. 心脏杂志, 2012, 24(6): 749-752.Xu B, Liu JC, Yu SQ, et al. Clinical study of warfarin anticoagulant therapy in Chinese patients aftermechanical heart valve replacement. Chin Heart J, 2012, 24(6): 749-752.
25.	Rosove MH, Grody WW. Should we be applying warfarin pharmacogenetics to clinical practice? No, not now. Ann Intern Med, 2009, 151(4): 270-273.

1. 高润霖. 中国心瓣膜病现状. 华西医学, 2018, 33(2): 127-131.Gao RL. Current status of valvular heart disease in China. West China Med J, 2018, 33(2): 127-131.
2. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: Executive summary: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation, 2021, 143(5): e35-e71.
3. International Warfarin Pharmacogenetics Consortium, Klein TE, Altman RB, et al. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med, 2009, 360(8): 753-764.
4. Bourgeois S, Jorgensen A, Zhang EJ, et al. A multi-factorial analysis of response to warfarin in a UK prospective cohort. Genome Med, 2016, 8(1): 2.
5. Spina E, Barbieri MA, Cicala G, et al. Clinically relevant drug interactions between newer antidepressants and oral anticoagulants. Expert Opin Drug Metab Toxicol, 2020, 16(1): 31-44.
6. Wang M, Zeraatkar D, Obeda M, et al. Drug-drug interactions with warfarin: A systematic review and meta-analysis. Br J Clin Pharmacol, 2021, 87(11): 4051-4100.
7. Wysowski DK, Nourjah P, Swartz L. Bleeding complications with warfarin use: A prevalent adverse effect resulting in regulatory action. Arch Intern Med, 2007, 167(13): 1414-1419.
8. Loebstein R, Yonath H, Peleg D, et al. Interindividual variability in sensitivity to warfarin: Nature or nurture? Clin Pharmacol Ther, 2001, 70(2): 159-164.
9. 中华医学会心血管病学分会, 中国老年学学会心脑血管病专业委员会. 华法林抗凝治疗的中国专家共识. 中华内科杂志, 2013, 52(1): 76-82.Chinese Society of Cardiology, Chinese Geriatrics Society. Chinese expert consensus on warfarin anticoagulation therapy. Chin J Intern Med, 2013, 52(1): 76-82.
10. Cheng TO. Chinese patients require lower dosage of warfarin. Int J Cardiol, 2010, 139(1): 1.
11. Zhou XM, Zhuang W, Hu JG, et al. Low-dose anticoagulation in Chinese patients with mechanical heart valves. Asian Cardiovasc Thorac Ann, 2005, 13(4): 341-344.
12. Cheung YF, Leung MP. Low dose oral anticoagulation therapy in Chinese children with congenital heart disease. J Paediatr Child Health, 1998, 34(6): 563-567.
13. 中华医学会胸心血管外科分会瓣膜病外科学组. 心脏瓣膜外科抗凝治疗中国专家共识. 中华胸心血管外科杂志, 2022, 38(3): 164-174.The Group of Valve Surgery, Chinese Society for Thoracic and Cardiovascular Surgery. Consensus of Chinese experts on anticoagulant therapy in cardiac valve surgery. Chin J Thorac Cardiovasc Surg, 2022, 38(3): 164-174.
14. 洪珊珊, 严美华, 傅新阳, 等. 心脏瓣膜置换术后服用华法林致出血的危险因素分析. 中外医疗, 2022, 41(35): 54-58.Hong SS, Yan MH, Fu XY, et al. Risk factors of warfarin bleeding after heart valve replacement. Chin Foreign Med Res, 2022, 41(35): 54-58.
15. 张进华, 刘茂柏, 蔡铭智, 等. 模型引导的华法林精准用药: 中国专家共识(2022版). 中国临床药理学与治疗学, 2022, 27(11): 1201-1212.Zhang JH, Liu MB, Cai MZ, et al. Model informed precision dosing of warfarin: China expert consensus re-port (2022 version). Chin J Clin Pharmacol Ther, 2022, 27(11): 1201-1212.
16. 屈清荣, 凡中霞, 李颖颖, 等. 心脏机械瓣膜置换术后患者华法林抗凝并发症的发生率及其影响因素分析. 护士进修杂志, 2014, 29(6): 518-521.Qu QR, Fan ZX, Li YY, et al. Analysis of the incidence and influencing factors of warfarin anticoagulation complications in patients after mechanical heart valve replacement. J Nurses Train, 2014, 29(6): 518-521.
17. 贾晓英, 韩艳艳, 王晓锋. 心脏机械瓣膜置换术后华法林抗凝治疗效果及INR抗凝强度范围分析. 现代诊断与治疗, 2020, 31(12): 1918-1920.Jia XY, Han YY, Wang XF. Analysis of the efficacy of warfarin anticoagulation therapy and INR anticoagulation intensity range after mechanical heart valve replacement. Mod Diagn Treat, 2020, 31(12): 1918-1920.
18. 许建屏, 石应康, 董力, 等. 中国人心脏瓣膜置换术后低强度抗凝治疗3000例随访1年报告. 四川大学学报(医学版), 2016, 47(1): 90-92.Xu JP, Shi YK, Dong L, et al. Low intensity anticoagulation therapy for chinese population with heart valve replacement: 3 000 cases follow-up. J Sichuan Univ (Med Sci Ed), 2016, 47(1): 90-92.
19. 董力, 石应康, 许建屏, 等. 中国心脏瓣膜术后多中心低强度抗凝治疗注册登记及随访研究. 中华医学杂志, 2016, 96(19): 1489-1494.Dong L, Shi YK, Xu JP, et al. The multicenter study on the registration and follow-up of low anticoagulation therapy for the heart valve operation in China. Natl Med J China, 2016, 96(19): 1489-1494.
20. Wei M, Ye F, Xie D, et al. A new algorithm to predict warfarin dose from polymorphisms of CYP4F2, CYP2C9 and VKORC1 and clinical variables: Derivation in Han Chinese patients with non valvular atrial fibrillation. Thromb Haemost, 2012, 107(6): 1083-1091.
21. Wells PS, Majeed H, Kassem S, et al. A regression model to predict warfarin dose from clinical variables and polymorphisms in CYP2C9, CYP4F2, and VKORC1: Derivation in a sample with predominantly a history of venous thromboembolism. Thromb Res, 2010, 125(6): e259-e264.
22. Tao Y, Chen YJ, Fu X, et al. Evolutionary ensemble learning algorithm to modeling of warfarin dose prediction for Chinese. IEEE J Biomed Health Inform, 2019, 23(1): 395-406.
23. 张春雨. PT、APTT、TT、Fg检测及临床应用. 中国实用医药, 2015, 10(7): 108-109.Zhang CY. Detection and clinical application of PT, APTT, TT, and Fg. China Pract Med, 2015, 10(7): 108-109.
24. 徐博, 刘金成, 俞世强, 等. 人工机械心脏瓣膜置换术后抗凝治疗强度与并发症发生率的关系. 心脏杂志, 2012, 24(6): 749-752.Xu B, Liu JC, Yu SQ, et al. Clinical study of warfarin anticoagulant therapy in Chinese patients aftermechanical heart valve replacement. Chin Heart J, 2012, 24(6): 749-752.
25. Rosove MH, Grody WW. Should we be applying warfarin pharmacogenetics to clinical practice? No, not now. Ann Intern Med, 2009, 151(4): 270-273.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Latest ArticlesAnalysis of factors for international normalized ratio levels>3.0 in patients undergoing warfarin anticoagulation therapy after mechanical heart valve replacement

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