Early evaluation of quality of anticoagulant therapy in patients with mechanical prosthetic valve replacement through TTR and FTTR_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

HEFan ^1,2 , RENRong ¹ , LIUGuanjian ³ , DENGYundan ¹ , LINFushun ¹ ,  XIAOXijun ¹

1. Division of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, 610041, P.R.China;
2. Cardiovascular Surgery Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310020, P.R.China;
3. Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu, 610041, P.R.China;

Corresponding?author：

XIAOXijun, Email: xijun.xiao@yahoo.com.cn

Keywords：

Mechanical heart valve replacement; early anticoagulation; warfarin; time in therapeutic range; fraction of time in therapeutic range

DOI：

10.7507/1007-4848.201502022

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Objective To evaluate the quality of anticoagulant therapy in patients with mechanical prosthetic valve replacement during early period through time in therapeutic range(TTR) and fraction of time in therapeutic range(FTTR), and to provide an objective evidence for further improving quality of anticoagulant therapy. Methods All the patients were followed and registered in hospital and at outpatient clinic from July 2012 through April 2014, with a maximum of 6 months after surgery. Targeted international normalized rate (INR) was 1.60 to 2.20, acceptable INR was 1.50 to 2.30. And warfarin weekly dosage adjustment was used as the strategy of anticoagulation management. Adjusting the warfarin dosage when INR was beyond acceptable INR. Events of bleeding, thrombogenesis and thromboembolism, TTR and FTTR of these patients during the follow-up were collected to evaluate quality of anticoagulant therapy in these patients. Results A total 477 patients and 2 755 reports of INR values were included for data analysis. The follow-up time was 78 918 days. Values of INR varied from 0.92 to 7.72(1.83±0.64). Required weekly doses of warfarin in target INR and acceptable INR were 5.00–35.00(18.15±3.99) mg/week and 5.00–39.38(18.29±4.08) mg/week. TTR of target INR and acceptable INR was 36.85%(27 079.5 d/78 918.0 d) and 49.84% (39 331.5 d/78 918.0 d), respectively. FTTR of target INR and acceptable INR was 37.31% (1 028 times/2 755 times), 50.01% (1 378 times/2 755 times), respectively. TTR of target INR and acceptable INR was 46.04%(3 902.5 d/8 475.5 d), 59.49%(5 042 d/8 475.5 d) when the patients’ follow-up was up to six months and FTTR of target INR and acceptable INR value of these patients was 46.81%(206 times/440 times), 60.45%(266 times/440 times). During the follow-up, there were 3 thromboembolism events, 1 transient physical abnormal activity, and 1 thrombogenesis in the left atrium, and there was no bleeding and death events. Conclusion The strategy of anticoagulation management used in our study is reasonable. In order to further improve the patients’ quality of anticoagulant therapy, it is necessary to start anticoagulation after operation as soon as possible, to strengthen the education of patients with anticoagulant knowledge and to increase INR test frequency properly.

Citation： HEFan, RENRong, LIUGuanjian, DENGYundan, LINFushun, XIAOXijun. Early evaluation of quality of anticoagulant therapy in patients with mechanical prosthetic valve replacement through TTR and FTTR. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2017, 24(2): 110-117. doi: 10.7507/1007-4848.201502022 Copy

1.	Khoury G, Sheikh-Taha M. Effect of age and sex on warfarin dosing. Clin Pharmacol, 2014, 6: 103-106.
2.	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.
3.	Herijgers P, Verhamme P. Improving the quality of anticoagulant therapy in patients with mechanical heart valves: what are we waiting for? Eur Heart J, 2007, 28(20): 2424-2426.
4.	Koertke H, Minami K, Boethig D,et al. INR self-management permits lower anticoagulation levels after mechanical heart valve replacement. Circulation, 2003, 108(10 suppl 1): II75-II78.
5.	Kulik A, Rubens FD, Wells PS,et al. Early postoperative anticoagulation after mechanical valve replacement: a systematic review. Ann Thorac Surg, 2006, 81(2): 770-781.
6.	肖錫俊, 劉關鍵, 梁茂植, 等. 機械瓣置換術后患者目標INR 1.60~2.20及以每周為單位華法林劑量調整合理性的初步評價. 中國循證醫學雜志, 2014, 14(1): 16-20.
7.	Heras M, Chesebro JH, Fuster V,et al. High risk of thromboemboli early after bioprosthetic cardiac valve replacement. J Am Coll Cardiol, 1995, 25(5): 1111-1119.
8.	Senning A. Alterations in Valvular Surgery: Biologic Valves. In Cohn LA, Gallucci V, Chief editor. Cardiac Bioprostheses: Proceedings of the Second International Symposium. New York: Yorke Medical Books. 1982.
9.	Meijer K, Kim YK, Schulman S. Decreasing warfarin sensitivity during the first three months after heart valve surgery: Implications for dosing. Throm Res, 2010, 125(3): 224-229.
10.	Butchart EG, Lewis PA, Kulatilake EN,et al. Anticoagulation variability between centres: implications for comparative prosthetic valve assessment. Eur J Cardiothorac Surg, 1987, 2(2): 72-81.
11.	Butchart EG, Lewis PA, Bethel JA,et al. Adjusting anticoagulation to prosthesis thrombogenicity and patient risk factors. Recommendations for the Medtronic Hall valve. Circulation, 1991, 84(5 Suppl): III61-III69.
12.	Kuntze CE, Ebels T, Eijgelaar A,et al. Rates of thromboembolism with three different mechanical heart valve prostheses: randomised study. Lancet, 1989, 333(8637): 514-517.
13.	刁明強, 董力. 心臟機械瓣膜置換術后早期抗凝及監測. 中國胸心血管外科臨床雜志, 2005, 12(2): 110-113.
14.	聶艷霞, 張志彪, 李娟, 等. 影響華法林抗凝作用的因素. 血栓與止血學, 2007, 13(4): 170-172.
15.	Chuan Q, Xiao YB, Chen L,et al. Anticoagulation early after mechanical heart valve replacement. J Med Coll PLA, 2010, 25(1): 24-28.
16.	Emery RW, Erickson CA, Arom KV,et al. Replacement of the aortic valve in patients under 50 years of age: long-term follow-up of the St.Jude Medical prosthesis. Ann Thorac Surg, 2003, 75(6): 1815-1819.
17.	Ageno W, Turpie AG. Exaggerated initial response to warfarin following heart valve replacement. Am J Cardiol, 1999, 84(8): 905-908.
18.	American College of Cardiology/American Heart Association Task Force on Practice Guidelines, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons,et al. 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) developed in collaboration with the Society of Cardiovascular Anesthesiologists endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. J Am Coll Cardiol, 2006, 48(3): e1-e148.
19.	Bayliss A, Faber P, Dunning J,et al. What is the optimal level of anticoagulation in adult patients receiving warfarin following implantation of a mechanical prosthetic mitral valve? Interact Cardiovasc Thorac Surg, 2007, 6(3): 390-396.
20.	Fukui T, Shibata T, Sasaki Y,et al. Long-term experience with the Sorin Bicarbon and Edwards Mira mechanical valve prostheses in the mitral position. Gen Thorac Cardiovasc Surg, 2007, 55(3): 91-97.
21.	Eriksson N, Wadelius M. Prediction of warfarin dose: why, when and how? Pharmacogenomics, 2012, 13(4): 429-440.
22.	Emery RW, Emery AM, Raikar GV,et al. Anticoagulation for mechanical heart valves: a role for patient based therapy. J Thromb Thrombolysis, 2008, 25(1): 18-25.
23.	Dunning J, Versteegh M, Fabbri A,et al. Guideline on antiplatelet and anticoagulation management in cardiac surgery. Eur J Cardio-Thorac Surg, 2008, 34(1): 73-92.
24.	Hirsh J, Dalen JE, Anderson DR,et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest, 1998, 114(5 Suppl): 445S-469S.
25.	Yamaguchi T. Optimal intensity of warfarin therapy for secondary prevention of stroke in patients with nonvalvular atrial fibrillation a multicenter, prospective, randomized trial. Stroke, 2000, 31(4): 817-821.
26.	Yu HC, Chan TY, Critchley JA,et al. Factors determining the maintenance dose of warfarin in Chinese patients. QJM, 1996, 89(2): 127-136.
27.	Gan GG, Teh A, Goh KY,et al. Racial background is a determinant factor in the maintenance dosage of warfarin. Int J Hematol, 2003, 78(1): 84-86.
28.	Cheung Y, Leung M. Low dose oral anticoagulation therapy in Chinese children with congenital heart disease. J Paediatr Child Health, 1998, 34(6): 563-567.
29.	Chenhsu RY, Chiang SC, Chou MH,et al. Long-term treatment with warfarin in Chinese population. Ann Pharmacother, 2000, 34(12): 1395-1401.
30.	劉美明, 吳樹明, 張希全. 心臟瓣膜置換術后早期抗凝劑量相關因素分析及臨床意義. 實用醫學雜志, 2005, 21(3): 273-274.
31.	Sun X, Hu S, Qi G,et al. Low standard oral anticoagulation therapy for Chinese patients with St.Jude mechanical heart valves. Chin Med J (Engl), 2003, 116(8): 1175-1178.
32.	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.
33.	唐躍, 吳清玉, 董超, 等. 機械瓣置換術后抗凝方法和凝血酶元國際標準化比值監測的臨床研究. 中華心血管病雜志, 2003, 31(6): 427-430.
34.	董力, 石應康, 田子樸, 等. 心臟機械瓣膜替換術后低強度抗凝治療. 中華外科雜志, 2004, 41(4): 250-252.
35.	Piper C, Horstkotte D. State of the art anticoagulation management. J Heart Valve Dis, 2004, 13(Suppl 1): S76-S80.
36.	Koudstaal P. Optimal oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and recent cerebral ischemia. N Engl J Med, 1995, 333(1): 5-10.
37.	Koertke H, Zittermann A, Wagner O,et al. Efficacy and safety of very low-dose self-management of oral anticoagulation in patients with mechanical heart valve replacement. Ann Thorac Surg, 2010, 90(5): 1487-1493.
38.	Samsa GP, Matchar DB. Relationship between test frequency and outcomes of anticoagulation: a literature review and commentary with implications for the design of randomized trials of patient self-management. J Thromb Thrombolysis, 2000, 9(3): 283-292.
39.	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.
40.	Njaastad AM, Abildgaard U, Lassen JF. Gains and losses of warfarin therapy as performed in an anticoagulation clinic. J Intern Med, 2006, 259(3): 296-304.
41.	Horstkotte D, Piper C, Wiemer M. Optimal frequency of patient monitoring and intensity of oral anticoagulation therapy in valvular heart disease. J Thromb Thrombolysis, 1998, 5(1): 19-24.
42.	Haibo Z, Jinzhong L, Yan L,et al. Low-intensity international normalized ratio (INR) oral anticoagulant therapy in Chinese patients with mechanical heart valve prostheses. Cell Biochem Biophys, 2012, 62(1): 147-151.
43.	Brehm K, Schack J, Heilmann C,et al. Mechanical heart valve recipients: anticoagulation in patients with genetic variations of phenprocoumon metabolism. Eur J Cardiothorac Surg, 2013, 44(2): 309-315.
44.	Zhou L, Wang S, Zhang Z,et al. Pharmacokinetic and pharmacodynamic interaction of Danshen-Gegen extract with warfarin and aspirin. J Ethnopharmacol, 2012, 143(2): 648-655.
45.	Chan K, Lo AC, Yeung JH,et al. The effects of Danshen (Salvia miltiorrhiza) on pharmacokinetics and pharmacodynamics of warfarin in rats. J Pharm Pharmacol, 1995, 47(5): 402-406.
46.	Hirsh J, Fuster V, Ansell J,et al. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. J Am Coll Cardiol, 2003, 41(9): 1633-1652.
47.	Du Breuil AL, Umland EM. Outpatient management of anticoagulation therapy. Am Fam Physician, 2007, 75(7): 1031-1042.

1. Khoury G, Sheikh-Taha M. Effect of age and sex on warfarin dosing. Clin Pharmacol, 2014, 6: 103-106.
2. 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.
3. Herijgers P, Verhamme P. Improving the quality of anticoagulant therapy in patients with mechanical heart valves: what are we waiting for? Eur Heart J, 2007, 28(20): 2424-2426.
4. Koertke H, Minami K, Boethig D,et al. INR self-management permits lower anticoagulation levels after mechanical heart valve replacement. Circulation, 2003, 108(10 suppl 1): II75-II78.
5. Kulik A, Rubens FD, Wells PS,et al. Early postoperative anticoagulation after mechanical valve replacement: a systematic review. Ann Thorac Surg, 2006, 81(2): 770-781.
6. 肖錫俊, 劉關鍵, 梁茂植, 等. 機械瓣置換術后患者目標INR 1.60~2.20及以每周為單位華法林劑量調整合理性的初步評價. 中國循證醫學雜志, 2014, 14(1): 16-20.
7. Heras M, Chesebro JH, Fuster V,et al. High risk of thromboemboli early after bioprosthetic cardiac valve replacement. J Am Coll Cardiol, 1995, 25(5): 1111-1119.
8. Senning A. Alterations in Valvular Surgery: Biologic Valves. In Cohn LA, Gallucci V, Chief editor. Cardiac Bioprostheses: Proceedings of the Second International Symposium. New York: Yorke Medical Books. 1982.
9. Meijer K, Kim YK, Schulman S. Decreasing warfarin sensitivity during the first three months after heart valve surgery: Implications for dosing. Throm Res, 2010, 125(3): 224-229.
10. Butchart EG, Lewis PA, Kulatilake EN,et al. Anticoagulation variability between centres: implications for comparative prosthetic valve assessment. Eur J Cardiothorac Surg, 1987, 2(2): 72-81.
11. Butchart EG, Lewis PA, Bethel JA,et al. Adjusting anticoagulation to prosthesis thrombogenicity and patient risk factors. Recommendations for the Medtronic Hall valve. Circulation, 1991, 84(5 Suppl): III61-III69.
12. Kuntze CE, Ebels T, Eijgelaar A,et al. Rates of thromboembolism with three different mechanical heart valve prostheses: randomised study. Lancet, 1989, 333(8637): 514-517.
13. 刁明強, 董力. 心臟機械瓣膜置換術后早期抗凝及監測. 中國胸心血管外科臨床雜志, 2005, 12(2): 110-113.
14. 聶艷霞, 張志彪, 李娟, 等. 影響華法林抗凝作用的因素. 血栓與止血學, 2007, 13(4): 170-172.
15. Chuan Q, Xiao YB, Chen L,et al. Anticoagulation early after mechanical heart valve replacement. J Med Coll PLA, 2010, 25(1): 24-28.
16. Emery RW, Erickson CA, Arom KV,et al. Replacement of the aortic valve in patients under 50 years of age: long-term follow-up of the St.Jude Medical prosthesis. Ann Thorac Surg, 2003, 75(6): 1815-1819.
17. Ageno W, Turpie AG. Exaggerated initial response to warfarin following heart valve replacement. Am J Cardiol, 1999, 84(8): 905-908.
18. American College of Cardiology/American Heart Association Task Force on Practice Guidelines, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons,et al. 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) developed in collaboration with the Society of Cardiovascular Anesthesiologists endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. J Am Coll Cardiol, 2006, 48(3): e1-e148.
19. Bayliss A, Faber P, Dunning J,et al. What is the optimal level of anticoagulation in adult patients receiving warfarin following implantation of a mechanical prosthetic mitral valve? Interact Cardiovasc Thorac Surg, 2007, 6(3): 390-396.
20. Fukui T, Shibata T, Sasaki Y,et al. Long-term experience with the Sorin Bicarbon and Edwards Mira mechanical valve prostheses in the mitral position. Gen Thorac Cardiovasc Surg, 2007, 55(3): 91-97.
21. Eriksson N, Wadelius M. Prediction of warfarin dose: why, when and how? Pharmacogenomics, 2012, 13(4): 429-440.
22. Emery RW, Emery AM, Raikar GV,et al. Anticoagulation for mechanical heart valves: a role for patient based therapy. J Thromb Thrombolysis, 2008, 25(1): 18-25.
23. Dunning J, Versteegh M, Fabbri A,et al. Guideline on antiplatelet and anticoagulation management in cardiac surgery. Eur J Cardio-Thorac Surg, 2008, 34(1): 73-92.
24. Hirsh J, Dalen JE, Anderson DR,et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest, 1998, 114(5 Suppl): 445S-469S.
25. Yamaguchi T. Optimal intensity of warfarin therapy for secondary prevention of stroke in patients with nonvalvular atrial fibrillation a multicenter, prospective, randomized trial. Stroke, 2000, 31(4): 817-821.
26. Yu HC, Chan TY, Critchley JA,et al. Factors determining the maintenance dose of warfarin in Chinese patients. QJM, 1996, 89(2): 127-136.
27. Gan GG, Teh A, Goh KY,et al. Racial background is a determinant factor in the maintenance dosage of warfarin. Int J Hematol, 2003, 78(1): 84-86.
28. Cheung Y, Leung M. Low dose oral anticoagulation therapy in Chinese children with congenital heart disease. J Paediatr Child Health, 1998, 34(6): 563-567.
29. Chenhsu RY, Chiang SC, Chou MH,et al. Long-term treatment with warfarin in Chinese population. Ann Pharmacother, 2000, 34(12): 1395-1401.
30. 劉美明, 吳樹明, 張希全. 心臟瓣膜置換術后早期抗凝劑量相關因素分析及臨床意義. 實用醫學雜志, 2005, 21(3): 273-274.
31. Sun X, Hu S, Qi G,et al. Low standard oral anticoagulation therapy for Chinese patients with St.Jude mechanical heart valves. Chin Med J (Engl), 2003, 116(8): 1175-1178.
32. 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.
33. 唐躍, 吳清玉, 董超, 等. 機械瓣置換術后抗凝方法和凝血酶元國際標準化比值監測的臨床研究. 中華心血管病雜志, 2003, 31(6): 427-430.
34. 董力, 石應康, 田子樸, 等. 心臟機械瓣膜替換術后低強度抗凝治療. 中華外科雜志, 2004, 41(4): 250-252.
35. Piper C, Horstkotte D. State of the art anticoagulation management. J Heart Valve Dis, 2004, 13(Suppl 1): S76-S80.
36. Koudstaal P. Optimal oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and recent cerebral ischemia. N Engl J Med, 1995, 333(1): 5-10.
37. Koertke H, Zittermann A, Wagner O,et al. Efficacy and safety of very low-dose self-management of oral anticoagulation in patients with mechanical heart valve replacement. Ann Thorac Surg, 2010, 90(5): 1487-1493.
38. Samsa GP, Matchar DB. Relationship between test frequency and outcomes of anticoagulation: a literature review and commentary with implications for the design of randomized trials of patient self-management. J Thromb Thrombolysis, 2000, 9(3): 283-292.
39. 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.
40. Njaastad AM, Abildgaard U, Lassen JF. Gains and losses of warfarin therapy as performed in an anticoagulation clinic. J Intern Med, 2006, 259(3): 296-304.
41. Horstkotte D, Piper C, Wiemer M. Optimal frequency of patient monitoring and intensity of oral anticoagulation therapy in valvular heart disease. J Thromb Thrombolysis, 1998, 5(1): 19-24.
42. Haibo Z, Jinzhong L, Yan L,et al. Low-intensity international normalized ratio (INR) oral anticoagulant therapy in Chinese patients with mechanical heart valve prostheses. Cell Biochem Biophys, 2012, 62(1): 147-151.
43. Brehm K, Schack J, Heilmann C,et al. Mechanical heart valve recipients: anticoagulation in patients with genetic variations of phenprocoumon metabolism. Eur J Cardiothorac Surg, 2013, 44(2): 309-315.
44. Zhou L, Wang S, Zhang Z,et al. Pharmacokinetic and pharmacodynamic interaction of Danshen-Gegen extract with warfarin and aspirin. J Ethnopharmacol, 2012, 143(2): 648-655.
45. Chan K, Lo AC, Yeung JH,et al. The effects of Danshen (Salvia miltiorrhiza) on pharmacokinetics and pharmacodynamics of warfarin in rats. J Pharm Pharmacol, 1995, 47(5): 402-406.
46. Hirsh J, Fuster V, Ansell J,et al. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. J Am Coll Cardiol, 2003, 41(9): 1633-1652.
47. Du Breuil AL, Umland EM. Outpatient management of anticoagulation therapy. Am Fam Physician, 2007, 75(7): 1031-1042.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Early evaluation of quality of anticoagulant therapy in patients with mechanical prosthetic valve replacement through TTR and FTTR

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