Should warfarin be routinely prescribed for the first three months after a bioprosthetic valve replacement
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《血管的通路杂志》
a Department of Cardiothoracic Surgery, Queen Elizabeth Building, Alexandra Parade, Glasgow Royal Infirmary, G31 2ER, Glasgow, UK
b Department of Cardiothoracic Surgery, James Cook University Hospital, Middlesbrough, UK
Abstract
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether warfarin should be routinely prescribed for the first three months after a bioprosthetic valve replacement either for the aortic or mitral position. Altogether 620 papers were identified using the below-mentioned search. In addition, all major international guidelines were included. Fifteen papers presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group, relevant outcomes and weaknesses were tabulated. We conclude that all guidelines, the available evidence and current practice support the use of warfarin at an INR of 2–3 for 3 months for bioprosthetic mitral valve replacement (MVR). However, it must be acknowledged that this recommendation is based on only a small number of non-randomized cohort studies and on expert consensus. For patients without high risk factors undergoing a bioprosthetic aortic valve replacement (AVR), the European Society of Cardiology (ESC), the American College of Chest Physicians (ACCP) and the Scottish Intercollegiate Guidelines Network (SIGN) all recommend warfarin for 3 months after surgery. However, the American Heart Association (AHA/ACC) guidelines and the British Society for Haematology (BSH) regard aspirin alone as adequate therapy. In addition, two large surveys show that the majority of surgeons worldwide now use only antiplatelet therapy. The evidence from clinical studies to support the use of warfarin post-bioprosthetic AVR is very weak and out-dated, and therefore, we feel that it is certainly safe to use antiplatelet therapy alone post-bioprosthetic AVR.
Key Words: Warfarin; Bioprosthesis; Aortic valve; Mitral valve; Anticoagulants
1. Introduction
A best evidence topic was constructed according to the structured protocol. This protocol is fully described in the ICVTS [1].
2. Clinical scenario
You are consenting a 64-year-old lady for AVR. She is quite keen to go for a bioprosthesis as her mother was on warfarin in the past and it had ‘never agreed with her’. She is then quite disappointed when you tell her that she will actually have to be on warfarin for 3 months after the operation, and asks what would happen if she didn't take it. You can't quote her a figure of increased risk and therefore, resolve to look up the answer.
3. Three-part question
In patients undergoing a [bioprosthetic valve replacement] is [anticoagulation superior to antiplatelet therapy] for the prevention of [thromboembolism]
4. Search strategy
Medline 1966–May 2006
[exp. warfarin/OR exp. anticoagulants/OR anticoagulation.mp. OR antithrombo$.mp OR warfarin.mp OR vitaminK antagonist$.mp] AND [bioprosthesis.mp OR bioprostheses.mp OR bioprosthetic.mp OR tissue.mp] AND [exp. mitral valve/OR exp. aortic valve/OR exp. heart valve prosthesis/OR exp. heart valve prosthesis implantation/OR valve replacement.mp. OR AVR.mp OR MVR.mp] limit to humans.
5. Search outcome
A total of 620 abstracts were found. All major guidelines were also included and their reference lists searched. Fifteen papers were deemed to represent the best evidence on the topic (Table 1).
6. Discussion
The most recent guidelines have come from the European Society of Cardiologists in 2005 [2]. They recommend that due to the absence of studies that demonstrate the safety of omitting anticoagulation for 3 months post-bioprosthesis, warfarinisation with a target INR of 2.5 or 3.0 in higher risk patients should be given.
The ACCP guidelines from 2001 and updated in 2004 [3,4] recommend warfarin for 3 months for mitral bioprostheses, giving this a grade 1C+ recommendation, and in the aortic position they also recommend warfarin but give this a grade 2C recommendation. They recommend targeting an INR of 2.0–3.0 (Grade 1C).
The AHA/ACC guidelines published in 1998 [5,6] recommended that the highest risk of thromboembolism is in the days immediately post-operatively and thus heparin should be started followed by warfarin for 3 months. However, for patients with a bioprosthesis with no risk factors such as AF, EF<30%, thromboembolism, hypercoagulable state, aspirin with a dose of 80–100 mg/day may be given. This is a grade 1 recommendation.
In 1998 the Scottish Intercollegiate Guideline Network [7] recommended warfarin for 3 months for aortic bioprostheses (Grade C) and 3–6 months of warfarin for mitral bioprostheses (Grade A). They recommend an INR target of 2–3.
The British Society of Haematology produced guidelines in 1998 (that were unchanged in an update in 2005) [8] recommending that mitral bioprostheses receive 3–6 months of anticoagulation. However, they did not recommend warfarin for aortic bioprostheses although they acknowledged that many institutions did do this.
In contrast to the above guidelines that advise 3 months of warfarin therapy, two large surveys have shown that this is not routine practice for aortic valves. In 2004 CTSNet (www.ctsnet.org) [9] performed a survey, with 726 respondents worldwide and found that while 80% of surgeons were aware of current guidelines, 60% did not routinely give 3 months of warfarin. In addition, only 15% of surgeons felt that antiplatelets were not an acceptable alternative to warfarin and over 60% of surgeons thought that warfarin was no longer the standard of care for tissue aortic valves.
In 2005 Vaughan and Waterworth [10] performed a survey of UK surgeons. They found that 53% of consultants never use warfarin for bioprosthetic aortic valves, and 33% do not anticoagulate tissue valve replacements. Only 16% of surgeons followed ACCP guidelines.
Turning to the original papers, most recently Sundt et al. [11] from the Mayo Clinic in 2005 published a retrospective review of their practice with 1151 patients undergoing tissue AVR, half of whom were anticoagulated. In the 90-days post-surgery, 2.4% of those who were anticoagulated had a stroke compared to 1.9% of patients who were not anticoagulated. There was no difference in bleeding rates or reopening rates. They conclude that while they showed no significant benefit, they also showed no harm due to bleeding rates and acknowledged the underpowered nature of their study.
Gherli et al. [12] in 2004 published a study advocating the use of aspirin for tissue aortic valve replacements. They reported that in a study of 249 patients (of whom 108 patients received warfarin according to surgeon's preference) there was no difference in stroke rate. There was also no difference in bleeding rates. Of note only 4 aspirin and 8 warfarin patients had a stroke.
Heras et al. [13] reporting from the Mayo Clinic in 1995 provide much of the evidence quoted by the ACCP guidelines. They quote a rate of 50% thromboembolic events per year in the first 10 days after AVR without warfarin but none with warfarin, and for overall follow up for tissue MVR the event rate of 2.5%/year was significantly lower than 3.9%/year without warfarin. However, the significance of the data pertaining to AVRs has been called into question by authors from the same institution. Sundt et al. [11] stated that of the 424 patients who had a tissue AVR only 5 patients had a thromboembolic event in the first 10 days, and thereafter none of the AVR data demonstrated a significant difference.
Moinudeen et al. [14] reported in 185 patients that the rate of CVA/TIAs was 18% in both the aspirin and warfarin groups after a mean 5-year follow up. The bleeding rate was not significantly different. They concluded that warfarin was not required for AVR although again this study is too small to exclude the benefit of warfarin in this situation.
Mistiaen et al. [15] in 2004 analysed 500 elderly patients receiving a Carpentier–Edwards valve and found on multivariate analysis that use of warfarin actually increased the risk of thromboembolism with a risk ratio of 3.0 after 4-year follow up. While this was a study of 500 patients, only 30 patients in sinus rhythm actually received long-term warfarin, to form this high risk group (7 had a CVA).
Yao et al. [16] in 2003 reported that the 10-year freedom from thromboembolism for biological MVRs was 100% if they were anticoagulated for the whole period but only 71% if anticoagulation was not given. Of note there were only 22 patients in the anticoagulation group.
The ACCP guidelines quote the paper by Turpie et al. [17] from 1988 to demonstrate that 5% (2/40) of patients with an INR=2.5–4.0 and 5.1% (2/39) with an INR=2.0–2.3 had a thromboembolus after tissue MVR, but the bleeding rate was lower in the low INR group. This paper did not have a ‘no-anticoagulation’ arm. The study by Ionescu et al. from 1982 [18] is also quoted as evidence in favour of anticoagulation for tissue MVR. In this series of patients from 1971–1981, 5.9% (4/68) who did not receive anticoagulants and 0% (0/182) of patients who received warfarin had an ischemic event during the first 3 months.
7. Clinical bottom line
Patients post-bioprosthetic MVR should have warfarin for 3 months with an INR of 2–3. For patients post-bioprosthetic AVR without additional risk factors, antiplatelet therapy alone is adequate.
References
Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact Cardiovasc Thorac Surg 2003; 2:405–409.
Butchart EG, Gohlke-Barwolf C, Antunes MJ, Tornos P, De Caterina R, Cormier B, Prendergast B, Iung B, Bjornstad H, Leport C, Hall RJ, Vahanian A. Working groups on valvular heart disease, thrombosis, and cardiac rehabilitation and exercise physiology, European Society of Cardiology. Recommendations for the management of patients after heart valve surgery. Eur Heart J 2005; 26:2463–2471.
Stein PD, Alpert JS, Bussey HI, Dalen JE, Turpie AG. Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves. Chest 2001; 119:220S–227S.
Salem DN, Stein PD, Al-Ahmad A, Bussey HI, Horstkotte D, Miller N, Pauker SG. Antithrombotic therapy in valvular heart disease – native and prosthetic: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126:457S–482S.
Bonow RO, Carabello B, de Leon AC, Edmunds LH Jr, Fedderly BJ, Freed MD, Gaasch WH, McKay CR, Nishimura RA, O'Gara PT, O'Rourke RA, Rahimtoola SH, Ritchie JL, Cheitlin MD, Eagle KA, Gardner TJ, Garson A Jr, Gibbons RJ, Russell RO, Ryan TJ, Smith SC Jr. ACC/AHA Guidelines for the management of patients with valvular heart disease. Executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on management of patients with valvular heart disease). J Heart Valve Dis 1998; 7:672–707.
Bonow RO, Carabello B, de Leon AC Jr, Edmunds LH Jr, Fedderly BJ, Freed MD, Gaasch WH, McKay CR, Nishimura RA, O'Gara PT, O'Rourke RA, Rahimtoola SH, Ritchie JL, Cheitlin MD, Eagle KA, Gardner TJ, Garson A Jr, Gibbons RJ, Russell RO, Ryan TJ, Smith SC Jr. Guidelines for the management of patients with valvular heart disease: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on management of patients with valvular heart disease). Circulation 1998; 98:1949–1984.
Lowe G, Belch J, Burton C, Cachia P, Cook M, Cooke T, Forbes C, Greer I, Irving J, Ludlam C, McInnes G, Murray P, Sandercock P, Treasure I, Walker I, Webster J. Antithrombotic therapy. Scottish Intercollegiate Guidelines Network (SIGN), 1999;.
. British Society of Haematologists. Guidelines on oral anticoagulation: Third edition. Br J Haematol 1998; 101:374–387.
CTSNet editors. . Valve technology center. Anticoagulation therapy after aortic tissue valve replacement. The Cardiothoracic Surgery Network (CTSNet) 2004;.
Vaughan P, Waterworth PD. An audit of anticoagulation practice among UK cardiothoracic consultant surgeons following valve replacement/repair. J Heart Valve Dis 2005; 14:576–582.
Sundt TM, Zehr KJ, Dearani JA, Daly RC, Mullany CJ, McGregor CG, Puga FJ, Orszulak TA, Schaff HV. Is early anticoagulation with warfarin necessary after bioprosthetic aortic valve replacement J Thorac Cardiovasc Surg 2005; 129:1024–1031.
Gherli T, Colli A, Fragnito C, Nicolini F, Borrello B, Saccani S, D'Amico R, Beghi C. Comparing warfarin with aspirin after biological aortic valve replacement: a prospective study. Circulation 2004; 110:496–500.
Heras M, Chesebro JH, Fuster V, Penny WJ, Grill DE, Bailey KR, Danielson GK, Orszulak TA, Pluth JR, Puga FJ, Schaff HV, Larsonkeller JJ. High risk of thromboemboli early after bioprosthetic cardiac valve replacement. J Am Coll Cardiol 1995; 25:1111–1119.
Moinuddeen K, Quin J, Shaw R, Dewar M, Tellides G, Kopf G, Elefteriades J. Anticoagulation is unnecessary after biological aortic valve replacement. Circulation 1998; 98:II95–98. discussion II98–99.
Mistiaen W, Van Cauwelaert P, Muylaert P, Sys SU, Harrisson F, Bortier H. Thromboembolic events after aortic valve replacement in elderly patients with a Carpentier-Edwards Perimount pericardial bioprosthesis. J Thorac Cardiovasc Surg 2004; 127:1166–1170.
Yao H, Miyamoto T, Mukai S, Yamamura M, Tanaka H, Nakagawa T, Ryomoto M, Inai Y, Yoshioka Y, Kaji M. Long-term results of mitral valve replacement: biological xenograft versus mechanical valves. J Artif Organs 2003; 6:30–36.
Turpie AG, Gunstensen J, Hirsh J, Nelson H, Gent M. Randomised comparison of two intensities of oral anticoagulant therapy after tissue heart valve replacement. Lancet 1988; 1:1242–1245.
Ionescu MI, Smith DR, Hasan SS, Chidambaram M, Tandon AP. Clinical durability of the pericardial xenograft valve: ten years experience with mitral replacement. Ann Thorac Surg 1982; 34:265–277.(Moataz El-Husseiny, Karee)
b Department of Cardiothoracic Surgery, James Cook University Hospital, Middlesbrough, UK
Abstract
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether warfarin should be routinely prescribed for the first three months after a bioprosthetic valve replacement either for the aortic or mitral position. Altogether 620 papers were identified using the below-mentioned search. In addition, all major international guidelines were included. Fifteen papers presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group, relevant outcomes and weaknesses were tabulated. We conclude that all guidelines, the available evidence and current practice support the use of warfarin at an INR of 2–3 for 3 months for bioprosthetic mitral valve replacement (MVR). However, it must be acknowledged that this recommendation is based on only a small number of non-randomized cohort studies and on expert consensus. For patients without high risk factors undergoing a bioprosthetic aortic valve replacement (AVR), the European Society of Cardiology (ESC), the American College of Chest Physicians (ACCP) and the Scottish Intercollegiate Guidelines Network (SIGN) all recommend warfarin for 3 months after surgery. However, the American Heart Association (AHA/ACC) guidelines and the British Society for Haematology (BSH) regard aspirin alone as adequate therapy. In addition, two large surveys show that the majority of surgeons worldwide now use only antiplatelet therapy. The evidence from clinical studies to support the use of warfarin post-bioprosthetic AVR is very weak and out-dated, and therefore, we feel that it is certainly safe to use antiplatelet therapy alone post-bioprosthetic AVR.
Key Words: Warfarin; Bioprosthesis; Aortic valve; Mitral valve; Anticoagulants
1. Introduction
A best evidence topic was constructed according to the structured protocol. This protocol is fully described in the ICVTS [1].
2. Clinical scenario
You are consenting a 64-year-old lady for AVR. She is quite keen to go for a bioprosthesis as her mother was on warfarin in the past and it had ‘never agreed with her’. She is then quite disappointed when you tell her that she will actually have to be on warfarin for 3 months after the operation, and asks what would happen if she didn't take it. You can't quote her a figure of increased risk and therefore, resolve to look up the answer.
3. Three-part question
In patients undergoing a [bioprosthetic valve replacement] is [anticoagulation superior to antiplatelet therapy] for the prevention of [thromboembolism]
4. Search strategy
Medline 1966–May 2006
[exp. warfarin/OR exp. anticoagulants/OR anticoagulation.mp. OR antithrombo$.mp OR warfarin.mp OR vitaminK antagonist$.mp] AND [bioprosthesis.mp OR bioprostheses.mp OR bioprosthetic.mp OR tissue.mp] AND [exp. mitral valve/OR exp. aortic valve/OR exp. heart valve prosthesis/OR exp. heart valve prosthesis implantation/OR valve replacement.mp. OR AVR.mp OR MVR.mp] limit to humans.
5. Search outcome
A total of 620 abstracts were found. All major guidelines were also included and their reference lists searched. Fifteen papers were deemed to represent the best evidence on the topic (Table 1).
6. Discussion
The most recent guidelines have come from the European Society of Cardiologists in 2005 [2]. They recommend that due to the absence of studies that demonstrate the safety of omitting anticoagulation for 3 months post-bioprosthesis, warfarinisation with a target INR of 2.5 or 3.0 in higher risk patients should be given.
The ACCP guidelines from 2001 and updated in 2004 [3,4] recommend warfarin for 3 months for mitral bioprostheses, giving this a grade 1C+ recommendation, and in the aortic position they also recommend warfarin but give this a grade 2C recommendation. They recommend targeting an INR of 2.0–3.0 (Grade 1C).
The AHA/ACC guidelines published in 1998 [5,6] recommended that the highest risk of thromboembolism is in the days immediately post-operatively and thus heparin should be started followed by warfarin for 3 months. However, for patients with a bioprosthesis with no risk factors such as AF, EF<30%, thromboembolism, hypercoagulable state, aspirin with a dose of 80–100 mg/day may be given. This is a grade 1 recommendation.
In 1998 the Scottish Intercollegiate Guideline Network [7] recommended warfarin for 3 months for aortic bioprostheses (Grade C) and 3–6 months of warfarin for mitral bioprostheses (Grade A). They recommend an INR target of 2–3.
The British Society of Haematology produced guidelines in 1998 (that were unchanged in an update in 2005) [8] recommending that mitral bioprostheses receive 3–6 months of anticoagulation. However, they did not recommend warfarin for aortic bioprostheses although they acknowledged that many institutions did do this.
In contrast to the above guidelines that advise 3 months of warfarin therapy, two large surveys have shown that this is not routine practice for aortic valves. In 2004 CTSNet (www.ctsnet.org) [9] performed a survey, with 726 respondents worldwide and found that while 80% of surgeons were aware of current guidelines, 60% did not routinely give 3 months of warfarin. In addition, only 15% of surgeons felt that antiplatelets were not an acceptable alternative to warfarin and over 60% of surgeons thought that warfarin was no longer the standard of care for tissue aortic valves.
In 2005 Vaughan and Waterworth [10] performed a survey of UK surgeons. They found that 53% of consultants never use warfarin for bioprosthetic aortic valves, and 33% do not anticoagulate tissue valve replacements. Only 16% of surgeons followed ACCP guidelines.
Turning to the original papers, most recently Sundt et al. [11] from the Mayo Clinic in 2005 published a retrospective review of their practice with 1151 patients undergoing tissue AVR, half of whom were anticoagulated. In the 90-days post-surgery, 2.4% of those who were anticoagulated had a stroke compared to 1.9% of patients who were not anticoagulated. There was no difference in bleeding rates or reopening rates. They conclude that while they showed no significant benefit, they also showed no harm due to bleeding rates and acknowledged the underpowered nature of their study.
Gherli et al. [12] in 2004 published a study advocating the use of aspirin for tissue aortic valve replacements. They reported that in a study of 249 patients (of whom 108 patients received warfarin according to surgeon's preference) there was no difference in stroke rate. There was also no difference in bleeding rates. Of note only 4 aspirin and 8 warfarin patients had a stroke.
Heras et al. [13] reporting from the Mayo Clinic in 1995 provide much of the evidence quoted by the ACCP guidelines. They quote a rate of 50% thromboembolic events per year in the first 10 days after AVR without warfarin but none with warfarin, and for overall follow up for tissue MVR the event rate of 2.5%/year was significantly lower than 3.9%/year without warfarin. However, the significance of the data pertaining to AVRs has been called into question by authors from the same institution. Sundt et al. [11] stated that of the 424 patients who had a tissue AVR only 5 patients had a thromboembolic event in the first 10 days, and thereafter none of the AVR data demonstrated a significant difference.
Moinudeen et al. [14] reported in 185 patients that the rate of CVA/TIAs was 18% in both the aspirin and warfarin groups after a mean 5-year follow up. The bleeding rate was not significantly different. They concluded that warfarin was not required for AVR although again this study is too small to exclude the benefit of warfarin in this situation.
Mistiaen et al. [15] in 2004 analysed 500 elderly patients receiving a Carpentier–Edwards valve and found on multivariate analysis that use of warfarin actually increased the risk of thromboembolism with a risk ratio of 3.0 after 4-year follow up. While this was a study of 500 patients, only 30 patients in sinus rhythm actually received long-term warfarin, to form this high risk group (7 had a CVA).
Yao et al. [16] in 2003 reported that the 10-year freedom from thromboembolism for biological MVRs was 100% if they were anticoagulated for the whole period but only 71% if anticoagulation was not given. Of note there were only 22 patients in the anticoagulation group.
The ACCP guidelines quote the paper by Turpie et al. [17] from 1988 to demonstrate that 5% (2/40) of patients with an INR=2.5–4.0 and 5.1% (2/39) with an INR=2.0–2.3 had a thromboembolus after tissue MVR, but the bleeding rate was lower in the low INR group. This paper did not have a ‘no-anticoagulation’ arm. The study by Ionescu et al. from 1982 [18] is also quoted as evidence in favour of anticoagulation for tissue MVR. In this series of patients from 1971–1981, 5.9% (4/68) who did not receive anticoagulants and 0% (0/182) of patients who received warfarin had an ischemic event during the first 3 months.
7. Clinical bottom line
Patients post-bioprosthetic MVR should have warfarin for 3 months with an INR of 2–3. For patients post-bioprosthetic AVR without additional risk factors, antiplatelet therapy alone is adequate.
References
Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact Cardiovasc Thorac Surg 2003; 2:405–409.
Butchart EG, Gohlke-Barwolf C, Antunes MJ, Tornos P, De Caterina R, Cormier B, Prendergast B, Iung B, Bjornstad H, Leport C, Hall RJ, Vahanian A. Working groups on valvular heart disease, thrombosis, and cardiac rehabilitation and exercise physiology, European Society of Cardiology. Recommendations for the management of patients after heart valve surgery. Eur Heart J 2005; 26:2463–2471.
Stein PD, Alpert JS, Bussey HI, Dalen JE, Turpie AG. Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves. Chest 2001; 119:220S–227S.
Salem DN, Stein PD, Al-Ahmad A, Bussey HI, Horstkotte D, Miller N, Pauker SG. Antithrombotic therapy in valvular heart disease – native and prosthetic: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126:457S–482S.
Bonow RO, Carabello B, de Leon AC, Edmunds LH Jr, Fedderly BJ, Freed MD, Gaasch WH, McKay CR, Nishimura RA, O'Gara PT, O'Rourke RA, Rahimtoola SH, Ritchie JL, Cheitlin MD, Eagle KA, Gardner TJ, Garson A Jr, Gibbons RJ, Russell RO, Ryan TJ, Smith SC Jr. ACC/AHA Guidelines for the management of patients with valvular heart disease. Executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on management of patients with valvular heart disease). J Heart Valve Dis 1998; 7:672–707.
Bonow RO, Carabello B, de Leon AC Jr, Edmunds LH Jr, Fedderly BJ, Freed MD, Gaasch WH, McKay CR, Nishimura RA, O'Gara PT, O'Rourke RA, Rahimtoola SH, Ritchie JL, Cheitlin MD, Eagle KA, Gardner TJ, Garson A Jr, Gibbons RJ, Russell RO, Ryan TJ, Smith SC Jr. Guidelines for the management of patients with valvular heart disease: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on management of patients with valvular heart disease). Circulation 1998; 98:1949–1984.
Lowe G, Belch J, Burton C, Cachia P, Cook M, Cooke T, Forbes C, Greer I, Irving J, Ludlam C, McInnes G, Murray P, Sandercock P, Treasure I, Walker I, Webster J. Antithrombotic therapy. Scottish Intercollegiate Guidelines Network (SIGN), 1999;.
. British Society of Haematologists. Guidelines on oral anticoagulation: Third edition. Br J Haematol 1998; 101:374–387.
CTSNet editors. . Valve technology center. Anticoagulation therapy after aortic tissue valve replacement. The Cardiothoracic Surgery Network (CTSNet) 2004;.
Vaughan P, Waterworth PD. An audit of anticoagulation practice among UK cardiothoracic consultant surgeons following valve replacement/repair. J Heart Valve Dis 2005; 14:576–582.
Sundt TM, Zehr KJ, Dearani JA, Daly RC, Mullany CJ, McGregor CG, Puga FJ, Orszulak TA, Schaff HV. Is early anticoagulation with warfarin necessary after bioprosthetic aortic valve replacement J Thorac Cardiovasc Surg 2005; 129:1024–1031.
Gherli T, Colli A, Fragnito C, Nicolini F, Borrello B, Saccani S, D'Amico R, Beghi C. Comparing warfarin with aspirin after biological aortic valve replacement: a prospective study. Circulation 2004; 110:496–500.
Heras M, Chesebro JH, Fuster V, Penny WJ, Grill DE, Bailey KR, Danielson GK, Orszulak TA, Pluth JR, Puga FJ, Schaff HV, Larsonkeller JJ. High risk of thromboemboli early after bioprosthetic cardiac valve replacement. J Am Coll Cardiol 1995; 25:1111–1119.
Moinuddeen K, Quin J, Shaw R, Dewar M, Tellides G, Kopf G, Elefteriades J. Anticoagulation is unnecessary after biological aortic valve replacement. Circulation 1998; 98:II95–98. discussion II98–99.
Mistiaen W, Van Cauwelaert P, Muylaert P, Sys SU, Harrisson F, Bortier H. Thromboembolic events after aortic valve replacement in elderly patients with a Carpentier-Edwards Perimount pericardial bioprosthesis. J Thorac Cardiovasc Surg 2004; 127:1166–1170.
Yao H, Miyamoto T, Mukai S, Yamamura M, Tanaka H, Nakagawa T, Ryomoto M, Inai Y, Yoshioka Y, Kaji M. Long-term results of mitral valve replacement: biological xenograft versus mechanical valves. J Artif Organs 2003; 6:30–36.
Turpie AG, Gunstensen J, Hirsh J, Nelson H, Gent M. Randomised comparison of two intensities of oral anticoagulant therapy after tissue heart valve replacement. Lancet 1988; 1:1242–1245.
Ionescu MI, Smith DR, Hasan SS, Chidambaram M, Tandon AP. Clinical durability of the pericardial xenograft valve: ten years experience with mitral replacement. Ann Thorac Surg 1982; 34:265–277.(Moataz El-Husseiny, Karee)