Chest ACCP Education Calendar
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stein, P. D.
Right arrow Articles by Turpie, A. G.G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stein, P. D.
Right arrow Articles by Turpie, A. G.G.
(Chest. 2001;119:220S-227S.)
© 2001 American College of Chest Physicians

Antithrombotic Therapy in Patients With Mechanical and Biological Prosthetic Heart Valves

Paul D. Stein, MD, FCCP; Joseph S. Alpert, MD, FCCP; Henry I. Bussey, Pharm D; James E. Dalen, MD, MPH, FCCP and Alexander G.G. Turpie, MD

Correspondence to: Paul D. Stein, MD, FCCP, Director of Research, St. Joseph Mercy-Oakland Hospital, 44555 Woodward Avenue (Suite 107), Pontiac, MI 48341-2964; e-mail:steinp{at}trinity-health.org


   Introduction
TOP
 Introduction
Mechanical Prosthetic Valves
 Bioprosthetic Valves
 Summary
 Recommendations
 References
 
In the present consensus report, we continue to address literature that may permit a more refined assessment of the optimal level of the international normalized ratio (INR) for patients with modern mechanical prosthetic heart valves. We address whether treatment with low doses of aspirin or other antithrombotic drugs, in combination with oral anticoagulants, may be beneficial. Investigations of low levels of warfarin are also assessed. Investigations included in the present report are generally limited to those that report antithrombotic prophylaxis in terms of the INR. Some investigations that relied on an estimation of the INR were also included, and these studies are identified.

Most of the published investigations lack data that would permit a firm conclusion about the optimal antithrombotic regimen for specific patients. Patients rarely were stratified according to additional risk factors associated with the type and location of prosthetic valves. Most results of antithrombotic prophylaxis are from nonrandomized case series without controls. The safety and efficacy of a given range of INR are usually reported on the basis of an intention-to-treat analysis rather than on the basis of the intensity of anticoagulation actually achieved. In some important investigations, less than half of the INRs were in the target range.1 2 These limitations weaken the basis on which therapeutic recommendations can be made. They also indicate a need for further research in this area. Prospective studies that address both the risk factors among patients with each type and location of prosthetic valve and the level of anticoagulation actually achieved are needed before controversy regarding prophylaxis can be resolved.


   Mechanical Prosthetic Valves
TOP
 Introduction
 Mechanical Prosthetic Valves
Bioprosthetic Valves
 Summary
 Recommendations
 References
 
St. Jude Medical Bileaflet Mechanical Valve
Experience with St. Jude Medical bileaflet mechanical valves is shown in Table 1 .3 4 5 6 Lack of prophylaxis gave unacceptable results.7 Horstkotte et al,3 in a study of patients with St. Jude Medical valves in the aortic position, showed that less intense anticoagulation, at an estimated INR of 1.8 to 2.8, in comparison to an estimated INR of 2.5 to 3.5, resulted in only a mild increase in the rate of thromboemboli (3.9%/yr vs 2.8%/yr) but a prominent reduction in the rate of major bleeding (0.4%/yr vs 1.2%/yr). Loss of atrial contraction had a pronounced effect on thromboembolic rates.8 Among patients, 86% of whom had St. Jude Medical valves, 96% of which were in the aortic position, thromboemboli were not more frequent at an INR of 2.0 to 3.0 than at an INR of 3.0 to 4.5, providing they were in sinus rhythm with a normal-sized left atrium.6


View this table:
[in this window]
[in a new window]

  		Table 1.. Thromboemboli With St. Jude Medical Bileaflet Mechanical Valves in Patients Who Received Prophylaxis With Coumarin Derivatives*

 
A case series by Cannegieter and associates,9 which included bileaflet valves in the aortic, mitral, or both positions, showed the fewest adverse effects, at an INR of 2.0 to 2.9.

A retrospective case series by Arom and associates,10 of patients age >= 70 years with St. Jude Medical aortic valves, showed a frequency of thromboemboli of 0.7%/yr, at an INR of 1.8 to 2.5. The INR was measured only during the later years of the investigation. The prevalence of atrial fibrillation was not stated.

Based on an analysis of published data, David et al11 concluded that there was no clinically important difference in the rate of systemic embolism among patients with the St. Jude Medical bileaflet valve and those with the CarboMedics bileaflet valve.

Tilting Disk Valves
In the aortic position, a low level of the INR (2.0 to 3.0) gave good results in a case series of patients with Medtronic-Hall valves.12 Regarding the Björk-Shiley spherical disk valve and the Björk-Shiley Convexo Concave valve, to our knowledge, there are no investigations that use an INR of 2.0 to 3.0. Therefore, whether a low level of INR can be used safely with such valves, particularly in the aortic position, is undetermined.

Tilting disk valves showed more thromboemboli when in the mitral position than in the aortic position (Table 2 ).12 13 14 15 16 Withholding prophylaxis, or the use of prophylaxis with antiplatelet agents alone in patients with the Björk-Shiley spherical disk valve, showed unsatisfactory results.17


View this table:
[in this window]
[in a new window]

  		Table 2.. Thromboemboli in Patients With Tilting Disk Valves Treated With Oral Anticoagulants*

 
Various Valves
Saour and associates,18 in a randomized trial among patients with various types of mechanical valves, did not show fewer thromboembolic events in patients treated with oral anticoagulants at an estimated INR of 7.4 to 10.8 than at an estimated INR of 1.9 to 3.6. More frequent minor bleeding, however, was shown at the higher INR, and a trend suggested more frequent major bleeding.

Pengo and associates,19 in a study of patients with various valves (estimated 74% tilting disk valves, 25% bileaflet valves, 1% ball valves) in the aortic, mitral, or both positions, reported a rate of thromboemboli of 1.8%/yr with an INR of 2.5 to 3.5 and a comparable rate of 2.1%/yr with an of INR 3.5 to 4.5.

An INR of 2.5 to 4.9 was optimal in a case series reported by Cannegieter et al.9 Most patients (77%) described by Cannegieter and associates had tilting disk valves. Some (3%) had caged ball or caged disk valves.9 The INR associated with the fewest adverse events was dependent on the number of valves, the location of the valve (mitral or aortic), and the type of valve (caged ball or disk, tilting disk, or bileaflet).

An analysis of results of several investigations of patients with various types of valves, based on estimates of the INR, suggests that an INR of 2.5 to 3.5 is satisfactory.20 The analysis demonstrated that a low thromboembolic rate with an acceptable hemorrhagic rate can be achieved at a minimum INR range of 2.5 to 3.0 and a maximum INR range of 2.5 to 3.6. Increasing the INR beyond 3.6 did not reduce the thromboembolic rates, but did increase the risk of hemorrhage.

Valve Position and Number of Valves
The prevalence of thromboemboli is higher with tilting disk prosthetic valves in the mitral position than in the aortic position (Table 2) . This is probably true with bileaflet mechanical valves as well, but data that used strict criteria for the measurement of the INR are sparse (Table 1) . Cannegieter et al,9 in a case series, showed an incidence of thromboembolism of 0.5%/yr with prosthetic aortic valves, 0.9%/yr with prosthetic mitral valves, and 1.2%/yr with both aortic and mitral valves. Irrespective of the type of mechanical valve, if the valve was in the aortic position, an INR of 2.0 to 2.9 gave results comparable to an INR of 3.0 to 3.9.9

Higher rates of thromboembolic complications with valves in the mitral position may be attributed to a higher incidence of atrial fibrillation, left atrial enlargement, and perhaps endocardial damage from rheumatic mitral valve disease.8 21 A low left ventricular ejection fraction, old age, and history of prior thromboembolism also are associated with thromboembolic complications.21

First-Generation Valves Compared With Modern Valves
The frequency of thromboemboli is lower with modern valves than with first-generation valves.9 The overall frequency of thromboemboli was 0.5%/yr with bileaflet valves, 0.7%/yr with tilting disk valves, and 2.5%/yr with caged ball and caged disk valves.9 Trends suggested that patients with bileaflet valves showed fewest adverse effects, with an INR of 2.0 to 2.9, whereas patients with tilting disk valves had fewest adverse effects at an INR of 3.0 to 3.9.9 Trends in patients with caged ball or caged disk valves showed the lowest frequency of adverse effects at an INR of 4.0 to 4.9.9 It has been suggested that such levels of the INR might be recommended in patients with caged ball or caged disk valves, but randomized trials are required to clarify this issue.9

Elderly Patients
Cannegieter and associates9 showed that the risk of thromboembolism was small among patients < 50 years of age (0.1%/yr). The frequency increased among patients 50 to 69 years of age (0.8%/yr), and the incidence was highest among patients >= 70 years of age (1.1%/yr).9 Even so, among elderly patients (>= 70 years of age), a retrospective case series suggested that a low level of oral anticoagulants was satisfactory with St. Jude Medical valves in the aortic position.10 Many of these patients were treated before the INR was in use, but in recent years, an INR of 1.8 to 2.5 resulted in a rate of thromboemboli of 0.7%/yr.

Children
Antithrombotic therapy in children with prosthetic heart valves is discussed in this supplement in an article entitled "Antithrombotic Therapy in Children" by Monagle et al (see page 344).

Anticoagulants and Bleeding
Data from several individual reports show varying frequencies of bleeding with increasing levels of the INR (Table 3 ).1 2 5 6 9 13 15 19 22 23 Cannegieter and associates9 showed that the incidence of hemorrhagic stroke increased once the INR rose to >= 4.0, and a sharp increase occurred at an INR of 5.0. Van der Meer and associates24 showed a sequentially increased rate of bleeding as the INR increased from 3.0 to 6.0. Among women, a sharp increased rate of bleeding occurred at an INR of 6.0 and higher.24 An observational study from a large anticoagulation clinic, where anticoagulants were used for a variety of indications in addition to prosthetic valves, showed that the risk of intracranial hemorrhage increased dramatically at an estimated INR of 4.0.25 The incidence of bleeding was higher among patients >= 70 years of age than in younger patients.9


View this table:
[in this window]
[in a new window]

  		Table 3.. Major Hemorrhage in Patients With Prosthetic Valves Treated With Oral Anticoagulants

 
Aspirin in Combination With Oral Anticoagulants
Turpie and associates,1 in a randomized trial, showed that aspirin 100 mg/d, in combination with oral anticoagulants at an INR of 3.0 to 4.5, was associated with fewer major systemic thromboemboli or death from vascular causes than oral anticoagulants alone, 1.9%/yr vs 8.5%/yr (p < 0.001). The rate of major bleeding, 8.5%/yr with aspirin plus oral anticoagulants vs 6.6%/yr with oral anticoagulants alone, was not statistically significantly different.

Meschengieser and associates,2 in a randomized trial, showed that aspirin 100 mg/d, in combination with oral anticoagulants at an INR of 2.5 to 3.5, was as effective as oral anticoagulants at an INR of 3.5 to 4.5. The frequency of thromboemboli or valve thrombosis was 1.3%/yr with aspirin in combination with the lower-intensity anticoagulation, and 1.5%/yr with the more intense anticoagulation without aspirin. Major bleeding was comparable—1.1%/yr with aspirin in combination with the lower-intensity anticoagulation, and 2.3%/yr with the more intense anticoagulation alone.

Meta-analysis supports the observation that the rate of thromboemboli is diminished with aspirin.26 Among the investigations reviewed in this meta-analysis, however, major bleeding was increased.

With an INR of 2.0 to 3.0 or 2.5 to 3.5, the frequency of bleeding is no greater with aspirin 325 mg to 660 mg/d than with 100 mg/d (Table 4 ).2 27 28 29 With an INR of 3.0 to 4.5, the risk of major hemorrhage may be high, irrespective of the use of aspirin.1 Low doses of aspirin did not increase the risk of major bleeding, but high doses of aspirin (660 mg/d) with an INR of 3.0 to 4.5 caused the risk of bleeding to be unacceptable.27 The combination of oral anticoagulants and aspirin may be particularly useful in patients with prosthetic valves who have coronary artery disease or stroke.2


View this table:
[in this window]
[in a new window]

  		Table 4.. Oral Anticoagulant Plus Aspirin and/or Dipyridamole in Patients With Aortic, Mitral, and Multiple Valves*

 
Dipyridamole in Combination With Oral Anticoagulants
We are aware of only one study in which dipyridamole was used in combination with warfarin at a known INR.30 Dipyridamole 300 mg/d was used in combination with warfarin (INR, 2.0 to 2.5) in a case series that included St. Jude Medical aortic, mitral, and two valves.30 The frequency of thromboemboli was 1.5%/yr.30 There was no control arm of that investigation.

A meta-analysis of six trials performed between 1971 and 1982, in which the INR is unknown, showed a reduction of fatal and nonfatal thromboemboli with dipyridamole in combination with oral anticoagulants.31

Katircioglu and associates32 used a fixed dose of warfarin, 2.5 mg/d, in combination with aspirin 100 mg/d and dipyridamole 225 mg/d. In patients with St. Jude Medical valves in the aortic position, they showed thromboemboli at a rate of 1.4%/yr and no valve thrombosis. Using somewhat more aspirin (250 mg/d), but otherwise the same regimen among patients with St. Jude Medical aortic valves, mitral valves, or two St. Jude valves, Yamak and associates33 showed a rate of 0.3%/yr valve thrombosis and 0.8%/yr thromboemboli. Others used dipyridamole in combination with aspirin, but no warfarin, in patients with St. Jude Medical aortic valves. They observed 1.6 to 2.1%/yr valve thrombosis and 0 to 1.6%/yr thromboemboli.34 35

Interruption of Anticoagulant Therapy, Major Surgery, Management of Patients Including Home Monitoring of INR, Management of Major Bleeding, Reversal of Anticoagulation With Vitamin K1, and Management of Pregnancy
These subjects are discussed in an article entitled "Oral Anticoagulants: Mechanism of Action, Clinical Effectiveness and Optimal Therapeutic Range" by Hirsh et al, in this supplement (see page 8), in the article "Use of Antithrombotic Agents During Pregnancy" by Ginsberg, Greer, Hirsh (see page 122), and in the article by Ansell et al, "Managing Oral Anticoagulant Therapy" (see page 22).


   Bioprosthetic Valves
TOP
 Introduction
 Mechanical Prosthetic Valves
 Bioprosthetic Valves
Summary
 Recommendations
 References
 
First 3 Months After Insertion in the Mitral Position
The frequency of thromboemboli has been high in the first 3 months after bioprosthetic valve insertion among patients not receiving antithrombotic therapy, particularly among patients with bioprosthetic valves in the mitral position.36 37 Among patients with bioprosthetic valves in the mitral position, Ionescu et al37 reported thromboemboli during the first 3 months after operation in 4 of 68 patients (5.9%) who did not receive anticoagulants and in 0 of 182 patients (0%) who received anticoagulants.

Heras and associates36 showed that oral anticoagulants (estimated INR, 3.0 to 4.5) in patients with bioprosthetic valves in the mitral position decreased the frequency of thromboemboli. However, the frequency remained high during the first 10 postoperative days.36 This may have been due to delay in achieving therapeutic levels of the INR. It was suggested that the early administration of heparin might explain why some groups observed lower rates of thromboemboli in patients who received short-term oral anticoagulants.36

Among patients with bioprosthetic valves in the mitral position, thromboemboli during the first 3 months occurred in 2 of 40 patients (5.0%), with an INR of 2.5 to 4.0 and in 2 of 39 patients (5.1%), with an INR of 2.0 to 2.3.38 These patients also received heparin 5,000 U every 12 h. All of the patients with thromboemboli had atrial fibrillation.38 Fewer bleeding complications occurred in the group that received oral anticoagulants at the lower INR. Other studies have shown that thromboemboli during the first 3 months after operation occurred despite adequate anticoagulation in patients with atrial fibrillation.39 Those with atrial fibrillation, a history of prior thromboembolism, or thrombi in the left atrium had higher rates of thromboemboli than patients with atrial fibrillation alone.39

First 3 Months After Insertion in the Aortic Position
Among patients with bioprosthetic valves in the aortic position, who received subcutaneous heparin 22,500 IU/d and aspirin 100 mg/d for the first 14 to 22 days after operation, but did not receive oral anticoagulants, the frequency of thromboemboli during the first 6 months was 1 occurrence out of 57 subjects (1.8%).40 Among patients who received oral anticoagulants and heparin 5,000 U subcutaneously every 12 h, 0 of 109 patients with prosthetic valves in the aortic position had thromboemboli during the first 3 months.38 However, some showed no advantage of early anticoagulation among patients with bioprosthetic valves in the aortic position.41 With no anticoagulation, 5 of 76 patients (6.6%) suffered cerebral ischemic events during the first 3 months after valve insertion, vs 8 of 109 patients (7.3%) among those who received postoperative heparin followed by warfarin.41

Long-term Results
Patients with bioprosthetic valves, whether porcine or pericardial, have a long term-risk for thromboemboli of 0.2 to 2.6%/yr (Table 5 ).42 43 44 45 46 47 48 49 50 51 52 The risk of thromboembolic stroke in patients with bioprosthetic valves in the aortic position is higher in patients with atrial fibrillation than in patients in sinus rhythm.53 In addition to atrial fibrillation, a low ejection fraction, large left atrium, and history of thromboembolism may be considered as potential risk factors for late-occurring thromboemboli in patients with all types of prosthetic valves.21 The need for pacemaker cardiostimulation also appears to increase the risk of thromboemboli in patients with bioprosthetic valves.54


View this table:
[in this window]
[in a new window]

  		Table 5.. Thromboemboli with Bioprosthetic Valves After the First 3 Months*

 
In a case series of 185 patients with bioprosthetic valves in the mitral or mitral-plus-aortic position who were in sinus rhythm and were treated long-term with aspirin 1 g daily or 500 mg every other day, no thromboemboli occurred in an average of 32 months.55 Also, no thromboemboli occurred in 31 patients, who had giant left atriums, who received aspirin.55 In a more recent case series in which 145 patients in sinus rhythm with porcine aortic valves received aspirin 75 mg/d, the rate of thromboemboli was 0.7%/yr.56

Thromboembolism in patients with bioprosthetic valves who are in atrial fibrillation presumably relates to both the bioprosthetic valve and the atrial fibrillation (see "Antithrombotic Therapy in Atrial Fibrillation," page 194, by Albers et al) The occurrence of thromboemboli in mostly untreated patients with bioprosthetic valves and atrial fibrillation was reported to be as high as 16% at36 months.57 Randomized trials in patients with atrial fibrillation who did not have prosthetic valves showed that long-term oral anticoagulants are effective, and they are more effective than aspirin (see article by Albers et al).


   Summary
TOP
 Introduction
 Mechanical Prosthetic Valves
 Bioprosthetic Valves
 Summary
Recommendations
 References
 

  1. Permanent therapy with oral anticoagulants offers the most consistent protection in patients with mechanical heart valves.
  2. Antiplatelet agents alone do not consistently protect patients with mechanical prosthetic heart valves, including patients in sinus rhythm with St. Jude Medical valves in the aortic position.
  3. Levels of oral anticoagulants that prolong the INR to 2.0 to 3.0 appear satisfactory for patients with St. Jude Medical bileaflet and Medtronic-Hall tilting disk mechanical valves in the aortic position, provided they are in sinus rhythm and the left atrium is not enlarged.3 6 12 Presumably, this is also true for the CarboMedics bileaflet valve, based on the observation of no clinically important difference in the rate of systemic embolism with this valve and the St. Jude Medical bileaflet valve.11
  4. Levels of oral anticoagulants that prolong the INR to 2.5 to 3.5 are satisfactory for tilting disk valves and bileaflet prosthetic valves in the mitral position.3 12 19 20
  5. Experience in patients with caged ball valves who had prothrombin time ratios reported in terms of the INR is sparse, because few such valves have been inserted in recent years.9 18 The number of surviving patients with caged ball valves continues to decrease. It has been suggested that the most advantageous level of the INR in patients with caged ball or caged disk valves should be as high as 4.0 to 4.9.9 However, others have shown a high rate of major hemorrhage with an INR that is even somewhat lower, 3.0–4.5.1 The problem is self-limited, however, because few such valves are being inserted.
  6. In patients with mechanical heart valves, aspirin, in addition to oral anticoagulants, has been shown to diminish the frequency of thromboemboli. The risk of bleeding is somewhat increased if the INR is 2.0 to 3.0 or 2.5 to 3.5. However, if the INR is 3.0 to 4.5, the risk of bleeding becomes excessive with aspirin. There are no investigations in which aspirin 80 mg/d in combination with oral anticoagulants was evaluated
  7. Data are insufficient to recommend dipyridamole over low doses of aspirin in combination with warfarin. Whether dipyridamole plus aspirin is more effective than aspirin alone when used with warfarin is undetermined.
  8. Patients with bioprosthetic valves in the mitral position as well as patients with bioprosthetic valves in the aortic position may be at risk for thromboemboli during the first 3 months after operation.36
  9. Among patients with bioprosthetic valves in the mitral position, oral anticoagulants at an INR of 2.0 to 2.3 were as effective as an INR of 2.5 to 4.0 and were associated with fewer bleeding complications during the first 3 months after operation.38
  10. Aspirin may reduce the long-term frequency of thromboembolism in patients with bioprosthetic valves.55 56


   Recommendations
TOP
 Introduction
 Mechanical Prosthetic Valves
 Bioprosthetic Valves
 Summary
 Recommendations
References
 
The following recommendations, in many instances, are made on the basis of sparse or incomplete data. As new data become available, the consensus recommendations may change. Treatment should always be based on appraisal of the individual patient, and it may properly differ from these consensus recommendations. The recommendations made by this committee differ somewhat from the recommendations of the European Society of Cardiology.58 In general, we recommend lower levels of the INR.

Mechanical Prosthetic Heart Valves

  1. We recommend that all patients with mechanical prosthetic heart valves receive oral anticoagulants (grade 1C+ recommendation)
  2. We recommend that unfractionated heparin or low molecular weight heparin be used until the INR is at a therapeutic level for 2 consecutive days (grade 2C)
  3. A target INR of 2.5 (range, 2.0 to 3.0) is recommended for patients with a St. Jude Medical bileaflet valve (grade 1A), Carbomedics bileaflet valve (grade 1C+) or Medtronic-Hall tilting disk mechanical valve (grade 1C+) in the aortic position, provided the left atrium is of normal size and the patient is in sinus rhythm.3 6 11 12
  4. Levels of oral anticoagulants that prolong the INR to a target of 3.0 (range, 2.5 to 3.5) are recommended for patients with tilting disk valves and bileaflet mechanical valves in the mitral position. (grade 1C+ recommendation)
  5. Levels of oral anticoagulants that prolong the INR to a target of 3.0 (range, 2.5 to 3.5) are recommended for patients with bileaflet mechanical aortic valves, who have atrial fibrillation (grade 1C+ recommendation, based on extrapolation of results in patients with atrial fibrillation who do not have prosthetic heart valves, and based on investigations in patients with mechanical heart valves who do not have atrial fibrillation).
  6. An alternative recommendation for patients with tilting disk valves, bileaflet mechanical valves in the mitral position, or bileaflet mechanical valves in the aortic position plus atrial fibrillation is a target INR of 2.5 (range, 2.0 to 3.0), in combination with aspirin 80 to 100 mg/d28 (grade 2C recommendation).
  7. A target INR of 3.0 (range, 2.5 to 3.5) in combination with aspirin 80 to 100 mg/d is recommended for patients with caged ball or caged disk valves (grade 2A recommendation, based on results of one randomized trial with various types of valves, one fourth of which were caged ball valves).2
  8. In patients who have mechanical valves and additional risk factors, we recommend a target INR of 3.0 (range, 2.5 to 3.5), combined with low doses of aspirin (80 to 100 mg/d) (grade 1C+ recommendation based on extrapolation of data from investigations, one of which used a different level of the INR, and the patients may not have had additional risk factors1 2 ).
  9. In view of the advantageous effects of low-dose aspirin in combination with oral anticoagulants, the indications for dipyridamole require further evaluation
  10. For patients with mechanical prosthetic heart valves who suffer systemic embolism despite adequate therapy with oral anticoagulants, we recommend aspirin 80 to 100 mg/d, in addition to oral anticoagulants, and maintenance of the INR at target of 3.0 (range 2.5 to 3.5) (grade 1C+ recommendation based on extrapolation of data, in which aspirin 100 mg/d was used, sometimes with a higher INR, in patients who did not have emboli1 2 ).

Bioprosthetic Heart Valves

  1. We recommend that patients with bioprosthetic valves in the mitral position be treated for the first 3 months after valve insertion with oral anticoagulants (grade 1C+ recommendation). We also recommend that patients with bioprosthetic valves in the aortic position be treated for the first 3 months after valve insertion with oral anticoagulants, but the evidence is less compelling (grade 2C recommendation).
  2. In view of the high risk of thromboembolism during the first 3 months after valve replacement, heparin (low molecular weight or unfractionated) might be used until the INR is at therapeutic levels for 2 consecutive days, but there is no evidence for this recommendation (grade 2C recommendation).
  3. We recommend a target INR of 2.5 (range, 2.0 to 3.0) during the first 3 months after operation in patients with bioprosthetic valves in the mitral or aortic position (grade 1A recommendation based on an investigation that used an INR of 2.0 to 2.3).38
  4. We recommended that patients with bioprosthetic valves who have atrial fibrillation be treated with long-term oral anticoagulants, at a dose sufficient to prolong the INR to 2.0 to 3.0 (goal 2.5). This 1C+ recommendation is based on randomized trials of patients with atrial fibrillation who did not have prosthetic heart valves (see article on atrial fibrillation). The need for anticoagulants is clear, based on these investigations. The dose of anticoagulants has not been established for patients with bioprosthetic valves and atrial fibrillation.
  5. In patients with bioprosthetic valves who have evidence of a left atrial thrombus at surgery, the consensus is to treat with long-term oral anticoagulants with a dose sufficient to prolong the INR to a target of 2.5 (range, 2.0 to 3.0)(grade 1C). The duration is uncertain. This grade 1C recommendation is not based on published studies. Patients with bioprosthetic valves who have a permanent pacemaker are also at high risk for thromboemboli, but there is no evidence that oral anticoagulants are protective.54 We suggest that anticoagulants (target INR 2.5; range, 2.0 to 3.0) are optional in such patients (grade 2C recommendation).
  6. It is recommended that patients with bioprosthetic valves who have a history of systemic embolism be treated with long-term oral anticoagulants. The INR and duration are uncertain. The consensus is to treat with oral anticoagulants 3 to 12 months, at doses sufficient to prolong the target INR to 2.5 (range, 2.5 to 3.0). This grade 2C recommendation is not based on published studies.
  7. Among patients with bioprosthetic valves who are in sinus rhythm, we recommend long-term therapy with aspirin 80 mg/d as protection against thromboembolism (grade 2C).56


   Footnotes
 
Abbreviation: INR = international normalized ratio


   References
TOP
 Introduction
 Mechanical Prosthetic Valves
 Bioprosthetic Valves
 Summary
 Recommendations
 References
 

  1. Turpie, AGG, Gent, M, Laupacis, A, et al (1993) Comparison of aspirin with placebo in patients treated with warfarin after heart-valve replacement. N Engl J Med 329,524-529[Abstract/Free Full Text]
  2. Meschengieser, SS, Carlos, GF, Santarelli, MT, et al (1997) Low-intensity oral anticoagulation plus low-dose aspirin versus high-intensity oral anticoagulation alone: a randomized trial in patients with mechanical prosthetic heart valves. J Thorac Cardiovasc Surg 113,910-916[Abstract/Free Full Text]
  3. Horstkotte, D, Schulte, HD, Bircks, W, et al (1994) Lower intensity anticoagulation therapy results in lower complication rates with the St. Jude Medical Prosthesis. J Thorac Cardiovasc Surg 107,1136-1145[Abstract/Free Full Text]
  4. Fiore, AC, Barner, HB, Swartz, MT, et al (1998) Mitral valve replacement: randomized trial of St. Jude and Medtronic Hall prostheses. Ann Thorac Surg 66,707-713[Abstract/Free Full Text]
  5. Vogt, S, Hoffmann, A, Roth, J, et al (1990) Heart valve replacement with the Björk-Shiley and St. Jude Medical prostheses: a randomized comparison in 178 patients. Eur Heart J 11,583-591[Abstract/Free Full Text]
  6. Acar, J, Iung, B, Boissel, JP, et al (1996) AREVA: Multicenter randomized comparison of low-dose versus standard dose anticoagulation in patients with mechanical prosthetic heart valves. Circulation 94,2107-2112[Abstract/Free Full Text]
  7. Baudet, EM, Oca, CC, Roques, XF, et al (1985) A 5 1/2 year experience with the St. Jude Medical cardiac valve prosthesis: early and late results of 737 valve replacements in 671 patients. J Thorac Cardiovasc Surg 90,137-144[Abstract]
  8. Horstkotte, D, Schulte, H, Bircks, W, et al (1993) Unexpected findings concerning thromboembolic complications and anticoagulation after complete 10 year follow up of patients with St. Jude Medical Prostheses. J Heart Valve Dis 2,291-301[Medline]
  9. Cannegieter, SC, Rosendaal, FR, Wintzen, AR, et al (1995) Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med 333,11-17[Abstract/Free Full Text]
  10. Arom, KV, Emery, RW, Nicoloff, DM, et al (1996) Anticoagulant related complications in elderly patients with St. Jude mechanical valve prostheses. J Heart Valve Dis 5,505-510[ISI][Medline]
  11. David, TE, Gott, VL, Harker, LA, et al (1996) Mechanical valves. Ann Thorac Surg 62,1567-1569[Free Full Text]
  12. Akins, CW (1996) Long-term results with the Medtronic-Hall valvular prosthesis. Ann Thorac Surg 61,806-813[Abstract/Free Full Text]
  13. Bloomfield, P, Wheatley, DJ, Prescott, RJ, et al (1991) Twelve-year comparison of a Björk-Shiley mechanical heart valve with porcine bioprostheses. N Engl J Med 324,573-579[Abstract]
  14. Sethia, B, Turner, MA, Lewis, S, et al (1986) Fourteen years’ experience with the Björk-Shiley tilting disc prosthesis. J Thorac Cardiovasc Surg 91,350-361[Abstract]
  15. Vallejo, JL, Gonzalez-Santos, JM, Albertos, J, et al (1990) Eight years’ experience with the Medtronic-Hall valve prosthesis. Ann Thorac Surg 50,429-436[Abstract]
  16. Aris, A, Igual, A, Padro, JM, et al (1996) The Spanish Monostrut Study Group: a ten-year experience with 8,599 implants. Ann Thorac Surg 62,40-47[Abstract/Free Full Text]
  17. Björk, VO, Henze, A (1975) Management of thrombo-embolism after aortic valve replacement with the Björk-Shiley tilting disc valve: medicamental prevention with dicumarol in comparison with dipyridamole-acetylsalicylic acid: surgical treatment of prosthetic thrombosis. Scand J Thorac Cardiovasc Surg 9,183-191[ISI][Medline]
  18. Saour, JN, Sieck, JO, Mamo, LAR, et al (1990) Trial of different intensities of anticoagulation in patients with prosthetic heart valves. N Engl J Med 322,428-432[Abstract]
  19. Pengo, V, Barbero, F, Banzato, A, et al (1997) A comparison of a moderate with moderate-high intensity oral anticoagulant treatment in patients with mechanical heart valve prostheses. Thromb Haemost 77,839-844[ISI][Medline]
  20. Stein, PD, Grandison, D, Hua, TA, et al (1994) Therapeutic level of oral anticoagulation with warfarin in patients with mechanical prosthetic heart valves: review of literature and recommendations based on international normalized ratio. Postgrad Med J 70(suppl 1),S72-S83
  21. Horstkotte, D, Scharf, RE, Schultheiss, HP (1995) Intracardiac thrombosis: patient-related and device-related factors. J Heart Valve Dis 4,114-120[Medline]
  22. Butchart, EG, Lewis, PA, Grunkemeier, GL, et al (1988) Low risk of thrombosis and serious embolic events despite low-intensity anticoagulation. Circulation 78(suppl I),I66-I77
  23. Gossinger, H, Neissner, H, Grubeck, B, et al (1986) Thromboembolism in patients with prosthetic heart valves: an adequately controlled intense anticoagulant therapy and its influence on the occurrence of thromboembolism in relation to valve type. Thorac Cardiovasc Surg 34,283-286[ISI][Medline]
  24. van der Meer, FJM, Rosendaal, FR, Vandenbroucke, JP, et al (1993) Bleeding complications in oral anticoagulant therapy: an analysis of risk factors. Arch Intern Med 153,1557-1562[Abstract]
  25. Hylek, EM, Singer, DE (1994) Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 120,897-902[Abstract/Free Full Text]
  26. Cappelleri, JC, Fiore, L, Brophy, M, et al (1995) Efficacy and safety of combined anticoagulant and antiplatelet therapy versus anticoagulant monotherapy after mechanical heart-valve replacement: a meta-analysis. Am Heart J 130,547-552[CrossRef][ISI][Medline]
  27. Altman, R, Rouvier, J, Gurfinkel, E, et al (1991) Comparison of two levels of anticoagulant therapy in patients with substitute heart valves. J Thorac Cardiovasc Surg 101,427-431[Abstract]
  28. Altman, R, Rouvier, J, Gurfinkel, E, et al (1996) Comparison of high-dose with low-dose aspirin in patients with mechanical heart valve replacement treated with oral anticoagulant. Circulation 94,2113-2116[Abstract/Free Full Text]
  29. Albertal, J, Sutton, M, Pereyra, D, et al (1993) Experience with moderate intensity anticoagulation and aspirin after mechanical valve replacement: a retrospective, non-randomized study. J Heart Valve Dis 2,302-307[Medline]
  30. Kontozis, L, Skudicky, D, Hopley, MJ, et al (1998) Long-term follow-up of St. Jude Medical prosthesis in a young rheumatic population using low-level warfarin anticoagulation: an analysis of the temporal distribution of causes of death. Am J Cardiol 81,736-739[CrossRef][ISI][Medline]
  31. Pouleur, H, Buyse, M (1995) Effects of dipyridamole in combination with anticoagulant therapy on survival and thromboembolic events in patients with prosthetic heart valves: a meta-analysis of the randomized trials. J Thorac Cardiovasc Surg 110,463-472[Abstract/Free Full Text]
  32. Katircioglu, SF, Yamak, B, Ulus, AT, et al (1997) Aortic valve replacement with the St. Jude Medical Prosthesis and fixed dose anticoagulation. J Card Surg 12,363-370[ISI][Medline]
  33. Yamak, B, Karagoz, HY, Zorlutuna, Y, et al (1993) Low-dose anticoagulant management of patients with St. Jude Medical mechanical valve prostheses. Thorac Cardiovasc Surg 41,38-42[ISI][Medline]
  34. Hartz, RS, LoCicero, J, III, Kucich, V, et al (1986) Comparative study of warfarin versus antiplatelet therapy in patients with a St. Jude Medical valve: the aortic position. J Thorac Cardiovasc Surg 92,684-690[Abstract]
  35. . et alRibeiro, PA, Al Zaibag, MA, Idris, M (1986) Antiplatelet drugs and the incidence of thromboembolic complications of the St. Jude Medical aortic prosthesis in patients with rheumatic heart disease. J Thorac Cardiovasc Surg 91,92-98[Abstract]
  36. Heras, M, Chesebro, JH, Fuster, V, et al (1995) High risk of early thromboemboli after bioprosthetic cardiac valve replacement. J Am Coll Cardiol 25,1111-1119[Abstract]
  37. Ionescu, MI, Smith, DR, Hasan, SS, et al (1982) Clinical durability of the pericardial xenograft valve: ten years experience with mitral replacement. Ann Thorac Surg 34,265-277[Abstract]
  38. Turpie, AGG, Gunstensen, J, Hirsh, J, et al (1988) Randomized comparison of two intensities of oral anticoagulant therapy after tissue heart valve replacement. Lancet 1,1242-1245[ISI][Medline]
  39. Hetzer, R, Topalidis, T, Borst, HG (1982) Thromboembolism and anticoagulation after isolated mitral valve replacement with porcine heterografts. Cohn, LH Gallucci, V eds. Proceedings, Second International Symposium on Cardiac Bioprostheses ,170-172 Yorke Medical Books New York.
  40. Babin-Ebell, J, Schmidt, W, Eigel, P, et al (1995) Aortic bioprosthesis without early anticoagulation—risk of thromboembolism. Thorac Cardiovasc Surg 43,212-214[ISI][Medline]
  41. Moinuddeen, K, Quin, J, Shaw, R, et al (1998) Anticoagulation is unnecessary after biological aortic valve replacement. Circulation 98,II-95–II-99
  42. Nakajima, H, Aupart, MR, Neville, PH, et al (1998) Twelve-year expericnce with the 19 mm Carpentier-Edwards pericardial aortic valve. J Heart Valve Dis 7,534-539[ISI][Medline]
  43. Banbury, MK, Cosgrove, DM, III, Lytle, BW, et al (1998) Long-term results of the Carpentier-Edwards pericardial aortic valve: a 12-year follow-up. Ann Thorac Surg 66(suppl),S73-S76
  44. Poirier, NC, Pelletier, LC, Pellerin, M, et al (1998) Fifteen-year experience with the Carpentier-Edwards pericardial bioprosthesis. Ann Thorac Surg 66(suppl),S57-S61
  45. Jamieson, WRE, Ling, H, Burr, LH, et al (1998) Carpentier-Edwards supraannular porcine bioprosthesis evaluation over 15 years. Ann Thorac Surg 66,S49-S52
  46. Glower, DD, Landolfo, KP, Cheruvu, S, et al (1998) Determinants of 15-year outcome with 1,119 standard Carpentier-Edwards porcine valves. Ann Thorac Surg 66(suppl),S44-S48
  47. Khan, SS, Chaux, A, Blanche, C, et al (1998) A 20-year experience with the Hancock porcine xenograft in the elderly. Ann Thorac Surg 66(suppl),S35-S39
  48. Neville, PH, Aupart, MR, Diemont, FF, et al (1998) Carpentier-Edwards pericardial bioprosthesis in aortic or mitral position: a 12-year experience. Ann Thorac Surg 66(suppl),S143-S147
  49. Jamieson, WRE, Burr, LH, Munro, AI, et al (1998) Carpentier-Edwards standard porcine bioprosthesis: a 21-year experience. Ann Thorac Surg 66(suppl),S40-S43
  50. Jamieson, WRE, Lemieux, MD, Sullivan, JA, et al (1998) Medtronic intact porcine bioprosthesis: 10 years’ experience. Ann Thorac Surg 66(suppl),S118-S121
  51. Borowiec, JW, Dubiel, TW, Hansson, H-E, et al (1998) Pericarbon pericardial valve prosthesis: midterm results of the aortic valve replacement. Angiology 49,1-11
  52. David, TE, Armstrong, S, Sun, Z (1998) The Hancock II bioprosthesis at 12 years. Ann Thorac Surg 66(suppl),S95-S98
  53. Cohn, LH, Collins, JJ, Jr, Rizzo, RJ, et al (1998) Twenty-year follow-up of the Hancock modified orifice porcine aortic valve. Ann Thorac Surg 66(suppl),S30-S41
  54. Louagie, YA, Jamart, J, Eucher, P, et al (1993) Mitral valve Carpentier-Edwards bioprosthetic replacement, thromboembolism, and anticoagulants. Ann Thorac Surg 56,931-937[Abstract]
  55. Nunez, L, Aguado, GM, Larrea, JL, et al (1984) Prevention of thromboembolism using aspirin after mitral valve replacement with porcine bioprosthesis. Ann Thorac Surg 37,84-87[Abstract]
  56. Goldsmith, I, Lip, GYH, Mukundan, S, et al (1998) Experience with low-dose aspirin as thromboprophylaxis for the Tissuemed porcine aortic bioprosthesis: a survey of five years’ expericnce. J Heart Valve Dis 7,574-579[ISI][Medline]
  57. Williams, JB, Karp, RB, Kirklin, JW, et al (1980) Considerations in selection and management of patients undergoing valve replacement with glutaraldehyde-fixed porcine bioprostheses. Ann Thorac Surg 30,247-258[Abstract]
  58. . Study Group of the Working Group on Valvular Heart Disease of the European Society of Cardiology (1995) Guidelines for prevention of thromboembolic events in valvular heart disease. Eur Heart J 16,1320-1330[Free Full Text]



This article has been cited by other articles:


Home page
 ICVTSHome page
M. El-Husseiny, K. Salhiyyah, S. G. Raja, and J. Dunning
Should warfarin be routinely prescribed for the first three months after a bioprosthetic valve replacement?
Interactive CardioVascular and Thoracic Surgery, October 1, 2006; 5(5): 616 - 623.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
R. O. Bonow, B. A. Carabello, K. Chatterjee, A. C. de Leon Jr, D. P. Faxon, M. D. Freed, W. H. Gaasch, B. W. Lytle, R. A. Nishimura, P. T. O'Gara, 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., August 1, 2006; 48(3): e1 - e148.
[Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
F. di Marco, M. Giordan, and G. Gerosa
Early antithrombotic therapy after aortic valve replacement with tissue valves: When the practice diverges from the guidelines
J. Thorac. Cardiovasc. Surg., June 1, 2006; 131(6): 1223 - 1223.
[Full Text] [PDF]

Home page
 Med Decis MakingHome page
K. M. Shermock, J. T. Connor, N. T. Smith, J. M. Fink, and L. Bragg
Validity of Criteria Used to Evaluate Fingerstick Devices That Assess International Normalized Ratio
Med Decis Making, May 1, 2006; 26(3): 239 - 246.
[Abstract] [PDF]

Home page
 Ann. Thorac. Surg.Home page
H. U. Jones, J. B. Muhlestein, K. W. Jones, D. G. Renlund, T. L. Bair, T. J. Bunch, B. D. Horne, D. L. Lappe, J. L. Anderson, and D. B. Doty
Early Postoperative Use of Unfractionated Heparin or Enoxaparin is Associated with Increased Surgical Re-Exploration for Bleeding
Ann. Thorac. Surg., August 1, 2005; 80(2): 518 - 522.
[Abstract] [Full Text] [PDF]

Home page
 Med Decis MakingHome page
M. H. Eckman
"Bridging On the River Kwai": The Perioperative Management of Anticoagulation Therapy
Med Decis Making, July 1, 2005; 25(4): 370 - 373.
[PDF]

Home page
 Ann. Thorac. Surg.Home page
H. Koertke, A. Zittermann, K. Minami, G. Tenderich, O. Wagner, M. El-Arousy, A. Krian, J. Ennker, U. Taborski, W. P. Klovekorn, et al.
Low-Dose International Normalized Ratio Self-Management: A Promising Tool to Achieve Low Complication Rates After Mechanical Heart Valve Replacement
Ann. Thorac. Surg., June 1, 2005; 79(6): 1909 - 1914.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
C. Stefanidis, A. M. Nana, D. De Canniere, M. Antoine, J.-L. Jansens, C.-H. Huynh, and J.-L. Le Clerc
10-Year Experience With the ATS Mechanical Valve in the Mitral Position
Ann. Thorac. Surg., June 1, 2005; 79(6): 1934 - 1938.
[Abstract] [Full Text] [PDF]

Home page
 Eur. J. Cardiothorac. Surg.Home page
J. I. Aramendi, C.-A. Mestres, J. Martinez-Leon, V. Campos, G. Munoz, and C. Navas
Triflusal versus oral anticoagulation for primary prevention of thromboembolism after bioprosthetic valve replacement (trac): prospective, randomized, co-operative trial
Eur. J. Cardiothorac. Surg., May 1, 2005; 27(5): 854 - 860.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
T.M. Sundt, K.J. Zehr, J.A. Dearani, R.C. Daly, C.J. Mullany, C.G.A. McGregor, F.J. Puga, T.A. Orszulak, and H.V. Schaff
Is early anticoagulation with warfarin necessary after bioprosthetic aortic valve replacement?
J. Thorac. Cardiovasc. Surg., May 1, 2005; 129(5): 1024 - 1031.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
E. G. Butchart and C. Gohlke-Barwolf
Anticoagulation management of patients with prosthetic valves
J. Am. Coll. Cardiol., September 1, 2004; 44(5): 1143 - 1144.
[Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
A. Sedrakyan, P. Hebert, V. Vaccarino, A. D. Paltiel, J. A. Elefteriades, J. Mattera, Z. Lin, S. A. Roumanis, and H. M. Krumholz
Quality of life after aortic valve replacement with tissue and mechanical implants
J. Thorac. Cardiovasc. Surg., August 1, 2004; 128(2): 266 - 272.
[Abstract] [Full Text] [PDF]

Home page
 J CARDIOVASC PHARMACOL THERHome page
U. Elkayam, H. Singh, A. Irani, and M. W. Akhter
Anticoagulation in Pregnant Women With Prosthetic Heart Valves
Journal of Cardiovascular Pharmacology and Therapeutics, April 1, 2004; 9(2): 107 - 115.
[Abstract] [PDF]

Home page
 J Am Coll CardiolHome page
R. Vink, R. A. Kraaijenhagen, B. A. Hutten, R. B. A. van den Brink, B. A. de Mol, H. R. Buller, and M. Levi
The optimal intensity of vitamin k antagonists in patients with mechanical heart valves: A meta-analysis
J. Am. Coll. Cardiol., December 17, 2003; 42(12): 2042 - 2048.
[Abstract] [Full Text] [PDF]

Home page
 HeartHome page
I Ferreira, L Dos, P Tornos, I Nicolau, G Permanyer-Miralda, and J Soler-Soler
Experience with enoxaparin in patients with mechanical heart valves who must withhold acenocumarol
Heart, May 1, 2003; 89(5): 527 - 530.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
R. W. Emery, G. J. Van Nooten, and P. J. Tesar
The initial experience with the ATS Medical mechanical cardiac valve prosthesis
Ann. Thorac. Surg., February 1, 2003; 75(2): 444 - 452.
[Abstract] [Full Text] [PDF]

Home page
 ASH Education BookHome page
A. I. Schafer, M. N. Levine, B. A. Konkle, and C. Kearon
Thrombotic Disorders: Diagnosis and Treatment
Hematology, January 1, 2003; 2003(1): 520 - 539.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
E. G. Butchart, N. Payne, H.-H. Li, K. Buchan, K. Mandana, and G. L. Grunkemeier
Better anticoagulation control improves survival after valve replacement
J. Thorac. Cardiovasc. Surg., April 1, 2002; 123(4): 715 - 723.
[Abstract] [Full Text]

Home page