Antithrombotic Therapy in Valvular Heart Disease—Native and Prosthetic: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy

doi:10.1378/chest.126.3_suppl.457S

Chest

Volume 126, Issue 3, Supplement, September 2004, Pages 457S-482S

https://doi.org/10.1378/chest.126.3_suppl.457S Get rights and content

This chapter about antithrombotic therapy in native and prosthetic valvular heart disease is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S–187S). Among the key recommendations in this chapter are the following: For patients with rheumatic mitral valve disease and atrial fibrillation (AF), or a history of previous systemic embolism, we recommend long-term oral anticoagulant (OAC) therapy (target international normalized ratio [INR], 2.5; range, 2.0 to 3.0) [Grade 1C+]. For patients with rheumatic mitral valve disease with AF or a history of systemic embolism who suffer systemic embolism while receiving OACs at a therapeutic INR, we recommend adding aspirin, 75 to 100 mg/d (Grade 1C). For those patients unable to take aspirin, we recommend adding dipyridamole, 400 mg/d, or clopidogrel (Grade 1C). In people with mitral valve prolapse (MVP) without history of systemic embolism, unexplained transient ischemic attacks (TIAs), or AF, we recommended against any antithrombotic therapy (Grade 1C). In patients with MVP and documented but unexplained TIAs, we recommend long-term aspirin therapy, 50 to 162 mg/d (Grade 1A). For all patients with mechanical prosthetic heart valves, we recommend vitamin K antagonists (Grade 1C+). For patients with a St. Jude Medical (St. Paul, MN) bileaflet valve in the aortic position, we recommend a target INR of 2.5 (range, 2.0 to 3.0) [Grade 1A]. For patients with tilting disk valves and bileaflet mechanical valves in the mitral position, we recommend a target INR of 3.0 (range, 2.5 to 3.5) [Grade 1C+]. For patients with caged ball or caged disk valves, we suggest a target INR of 3.0 (range, 2.5 to 3.5) in combination with aspirin, 75 to 100 mg/d (Grade 2A). For patients with bioprosthetic valves, we recommend vitamin K antagonists with a target INR of 2.5 (range, 2.0 to 3.0) for the first 3 months after valve insertion in the mitral position (Grade 1C+) and in the aortic position (Grade 2C). For patients with bioprosthetic valves who are in sinus rhythm and do not have AF, we recommend long-term (> 3 months) therapy with aspirin, 75 to 100 mg/d (Grade 1C+).

Section snippets

1.0 Rheumatic Mitral Valve Disease

The incidence of systemic embolism is greater in rheumatic mitral valve disease than in any other common form of valvular heart disease. While surgery and the frequent use of long-term anticoagulant therapy have altered the natural history of this disease during the past 40 years, Wood² cited a prevalence of systemic emboli of 9 to 14% in several large early series of mitral stenosis; in 1961, Ellis and Harken³ reported that 27% of 1,500 patients undergoing mitral valvuloplasty had a history of

Recommendations

For patients with rheumatic mitral valve disease and AF, or a history of previous systemic embolism:

1.1.1. We recommend long-term OAC therapy (target INR, 2.5; range, 2.0 to 3.0) [Grade 1C+].

For patients with rheumatic mitral valve disease and AF, or a history of previous systemic embolism:

1.1.2. We suggest clinicians not use concomitant therapy with an OAC and an antiplatelet agent (APA) [Grade 2C].

Underlying values and preferences: This recommendation places a relatively high value on

Recommendations

1.2.1. In patients with rheumatic mitral valve disease and normal sinus rhythm with a left atrial diameter > 5.5 cm, we suggest long-term OAC therapy (target INR, 2.5; range, 2.0 to 3.0) [Grade 2C].

Underlying values and preferences: This recommendation places a relatively high value on avoiding systemic embolism and its consequences, and a relatively low value on avoiding the bleeding risk and inconvenience associated with OAC therapy.

1.2.2. In patients with rheumatic mitral valve disease and

Recommendation

1.3.1. For patients undergoing mitral valvuloplasty, we suggest anticoagulation with vitamin K antagonists with a target INR of 2.5 (range, 2.0 to 3.0) for 3 weeks prior to the procedure and for 4 weeks after the procedure (Grade 2C).

2.0 Mitral Valve Prolapse

Mitral valve prolapse (MVP) is the most common form of valve disease in adults.⁴⁴ While generally innocuous, it is sometimes annoying, and serious complications can occur. During the past 20 years, embolic phenomena have been reported in several patients with MVP in whom no other source for emboli could be found. In 1974, Barnett⁴⁵ observed four patients with MVP who suffered cerebral ischemic events. Two years later, a total of 12 patients were described with recurrent transient ischemic

Recommendations

2.0.1. In people with MVP who have not experienced systemic embolism, unexplained TIAs, or AF, we recommended against any antithrombotic therapy (Grade 1C).

2.0.2. In patients with MVP who have documented but unexplained TIAs, we recommend long-term aspirin therapy, 50 to 162 mg/d (Grade 1A).

2.0.3. In patients with MVP who have documented systemic embolism or recurrent TIAs despite aspirin therapy, we suggest long-term vitamin K antagonist therapy (target INR, 2.5; range 2.0 to 3.0) [Grade 2C].

3.0 Mitral Annular Calcification

The clinical syndrome of mitral annular calcification (MAC), first clearly described in 1962,⁶³ includes a strong female preponderance and may be associated with mitral stenosis and regurgitation, calcific aortic stenosis, conduction disturbances, arrhythmias, embolic phenomena, and endocarditis. It must be emphasized that radiographic evidence of calcium in the mitral annulus does not in itself constitute the syndrome of MAC. While the true incidence of systemic emboli in this condition is not

Recommendation

3.0.1. In patients with MAC complicated by systemic embolism, not documented to be calcific embolism, we suggest treatment with long-term OAC therapy with a target INR of 2.5 (INR range, 2.0 to 3.0) [Grade 2C].

4.0 Aortic Valve and Aortic Arch Disorders

Clinically detectable systemic emboli in isolated aortic valve disease are distinctly uncommon. However, Stein et al⁷⁶ emphasized the thromboembolic potential of severe calcific aortic valve disease, and demonstrated microthrombi in 10 of 19 calcified and stenotic aortic valves studied histologically. In only one, however, was a thrombus grossly visible on the excised valve, and clinical evidence of systemic embolism was not reported. Four cases of calcific emboli to the retinal artery in

Recommendations

4.0.1. In patients with aortic valve disease, we suggest that clinicians not use long-term vitamin K antagonist therapy unless they have another indication for anticoagulation (Grade 2C).

4.0.2. We suggest OAC therapy in patients with mobile aortic atheromas and aortic plaques > 4 mm as measured by TEE (Grade 2C).

5.0 Prosthetic Heart Valves—Mechanical Prosthetic Heart Valves

It is well established that patients with all types of mechanical valves require antithrombotic prophylaxis. Lack of prophylaxis in patients with St. Jude Medical bileaflet valves gave unacceptable results (embolism or valve thrombosis in 12%/yr with aortic valves and 22%/yr with mitral valves).⁹³ Among patients with the Bjork Shiley spherical disk valves who received no prophylaxis or prophylaxis with APAs alone, thromboemboli occurred in 23%/yr.⁹⁴ In the present consensus report, we continue

Recommendations

5.1. For all patients with mechanical prosthetic heart valves, we recommend vitamin K antagonists (Grade 1C+). We suggest administration of unfractionated heparin or LMWH until the INR is stable and at a therapeutic level for 2 consecutive days (Grade 2C).

5.2. For patients with a St. Jude Medical bileaflet valve in the aortic position, we recommend a target INR of 2.5 (range, 2.0 to 3.0) [Grade 1A].

5.3. For patients with tilting disk valves and bileaflet mechanical valves in the mitral

6.1 First 3 months after valve insertion

The frequency of thromboemboli has been reported to be 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.¹⁵⁸¹⁵⁹ Among patients with bioprosthetic valves in the mitral position, Ionescu and associates¹⁵⁹ 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

Recommendations

6.1.1. For patients with bioprosthetic valves in the mitral position, we recommend vitamin K antagonists with a target INR of 2.5 (range, 2.0 to 3.0) for the first 3 months after valve insertion (Grade 1C+).

6.1.2. For patients with bioprosthetic valves in the aortic position, we suggest vitamin K antagonists with a target INR of 2.5 (range, 2.0 to 3.0) for the first 3 months after valve insertion or aspirin 80 to 100 mg/day (Grade 1C).

6.1.3. In patients who have undergone valve replacement, we

Recommendations

6.2.1. In patients with bioprosthetic valves who have AF, we recommend long-term treatment with vitamin K antagonists with a target INR of 2.5 (range, 2.0 to 3.0) [Grade 1C+].

6.2.2. For patients with bioprosthetic valves who are in sinus rhythm and do not have AF, we recommend long-term therapy with aspirin, 75 to 100 mg/d (Grade 1C+).

7.0 Infective Endocarditis and Nonbacterial Thrombotic Endocarditis

With the advent of effective antimicrobial therapy, the incidence of systemic emboli in infective endocarditis has decreased. In the preantibiotic era, clinically detectable emboli occurred in 70 to 97% of patients with infective endocarditis,¹⁸⁵ while, since that time, the prevalence has been reported to be 12 to 40%.¹⁸⁶¹⁸⁷¹⁸⁸¹⁸⁹¹⁹⁰¹⁹¹ Emboli occur more frequently in patients with acute endocarditis than in those with subacute disease,¹⁹² and the incidence of pulmonary emboli in right-sided

Recommendations

7.0.1. In patients with a mechanical prosthetic valve and endocarditis who have no contraindications, we suggest continuation of long-term vitamin K antagonists (Grade 2C).

7.0.2. For patients with NBTE and systemic or pulmonary emboli, we recommend treatment with full-dose unfractionated IV or subcutaneous heparin (Grade 1C).

7.0.3. For patients with disseminated cancer or debilitating disease with aseptic vegetations, we suggest administration of full-dose unfractionated heparin (Grade 2C).

8.0 Withdrawal of Anticoagulation Therapy Prior to Surgery

Patients with valvular heart disease receiving OAC therapy who require surgical procedures present special problems related to withholding and restarting anticoagulation therapy. The risks of bleeding vs thromboembolism as well as the costs must be carefully balanced. Eckman et al²²⁶ used decision analysis to examine the cost-effectiveness of varying strategies for treating patients with prosthetic heart valves undergoing noncardiac surgery. These authors concluded the marginal cost of

Summary

The decision to initiate long-term anticoagulant therapy in a patient with valvular heart disease is frequently difficult because of the many variables that influence the risks of thromboembolism and of bleeding in a given individual. The patient's age, the specific valve lesion, the heart rhythm, the duration of the valve disease, a history of thromboembolism, patient attitude and lifestyle, associated diseases, and medications all must be considered. In addition to these factors, for patients

References (234)

LB Ellis et al.
Arterial embolization in relation to mitral valvuloplasty
Am Heart J
(1961)
RC Hinton et al.
Influence of etiology of atrial fibrillation on incidence of systemic embolism
Am J Cardiol
(1977)
R Daley et al.
Systemic arterial embolism in rheumatic heart disease
Am Heart J
(1951)
HA Fleming
Anticoagulants in rheumatic heart disease
Lancet
(1971)
D Roy et al.
Usefulness of anticoagulant therapy in the prevention of embolic complications of atrial fibrillation
Am Heart J
(1986)
S Silaruks et al.
A prognostic model for predicting the disappearance of left atrial thrombi among candidates for percutaneous transvenous mitral commissurotomy
J Am Coll Cardiol
(2002)
P Petersen et al.
Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: the Copenhagen AFASAK study
Lancet
(1989)
SJ Connolly et al.
Canadian Atrial Fibrillation Anticoagulation (CAFA) Study
J Am Coll Cardiol
(1991)
JH Chesebro et al.
Trial of combined warfarin plus dipyridamole or aspirin therapy in prosthetic heart valve replacement: danger of aspirin compared with dipyridamole
Am J Cardiol
(1983)
J Dale et al.
Prevention of arterial thromboembolism with acetylsalicylic acid: a controlled clinical study in patients with aortic ball valves
Am Heart J
(1977)

J Hayashi et al.

Combined warfarin and antiplatelet therapy after St. Jude Medical valve replacement for mitral valve disease

J Am Coll Cardiol

(1994)

RA Grimm et al.

Should all patients undergo transesophageal echocardiography before electrical cardioversion of atrial fibrillation?

J Am Coll Cardiol

(1994)

DH Kang et al.

Comparison of outcomes of percutaneous mitral valvuloplasty versus mitral valve replacement after resolution of left atrial appendage thrombi by warfarin therapy

Am J Cardiol

(1998)

PK Fulkerson et al.

Calcification of the mitral annulus: etiology, clinical associations, complications and therapy

Am J Med

(1979)

PF Nestico et al.

Mitral annular calcification: clinical, pathophysiology, and echocardiographic review

Am Heart J

(1984)

LB Brockmeier et al.

Calcium emboli to the retinal artery in calcific aortic stenosis

Am Heart J

(1981)

DD Savage et al.

Prevalence of submitral (anular) calcium and its correlates in a general population-based sample (the Framingham Study)

Am J Cardiol

(1983)

Y Adler et al.

Association between mitral annulus calcification and aortic atheroma: a prospective transesophageal echocardiographic study

Atherosclerosis

(2000)

P Stein et al.

Continuing disease process of calcific aortic stenosis

Am J Cardiol

(1977)

R Daley et al.

Systemic arterial embolism in rheumatic heart disease

Am Heart J

(1951)

PA Tunick et al.

Atheromas of the thoracic aorta: clinical and therapeutic update

J Am Coll Cardiol

(2000)

E Ferrari et al.

Atherosclerosis of the thoracic aorta and aortic debris as a marker of poor prognosis: benefit of oral anticoagulants

J Am Coll Cardiol

(1999)

FA Dressler et al.

Mobile aortic atheroma and systemic emboli: efficacy of anticoagulation and influence of plaque morphology on recurrent stroke

J Am Coll Cardiol

(1998)

PA Tunick et al.

Effect of treatment on the incidence of stroke and other emboli in 519 patients with severe thoracic aortic plaque

Am J Cardiol

(2002)

EM Baudet et al.

Long-term results of valve replacement with the St. Jude Medical prosthesis

J Thorac Cardiovasc Surg

(1995)

PD Stein et al.

Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves [erratum appears in Chest 2001 Sep;120(3): 1044]

Chest

(2001)

SS Meschengieser et al.

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

(1997)

EM Baudet et al.

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

(1985)

P Laffort et al.

Early and long-term (one-year) effects of the association of aspirin and oral anticoagulant on thrombi and morbidity after replacement of the mitral valve with the St. Jude medical prosthesis: a clinical and transesophageal echocardiographic study

J Am Coll Cardiol

(2000)

PJ Devereaux et al.

Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation: observational study

BMJ

(2001)

P Wood

Diseases of the heart and circulation

(1956)

P Szekely

Systemic embolization and anticoagulant prophylaxis in rheumatic heart disease

BMJ

(1964)

PB Deverall et al.

Incidence of systemic embolism before and after mitral valvotomy

Thorax

(1968)

HJ Levine

Which atrial fibrillation patients should be on chronic anticoagulation?

J Cardiovasc Med

(1981)

AW Harris et al.

Cerebral emboli in mitral stenosis

Ann Intern Med

(1941)

N Coulshed et al.

Systemic embolism in mitral valve disease

Br Heart J

(1970)

K Cassella et al.

Patients with mitral stenosis and systemic emboli

Arch Intern Med

(1964)

HA Dewar et al.

A study of embolism in mitral valve disease and atrial fibrillation

Br Heart J

(1983)

WE Hay et al.

Age and atrial fibrillation as independent factors in auricular mural thrombus formation

Am Heart J

(1942)

Predictors of thromboembolism in atrial fibrillation: II

Echocardiographic features of patients at risk. The Stroke Prevention in Atrial Fibrillation Investigators

Ann Intern Med

(1992)

LR Caplan et al.

Atrial size, atrial fibrillation, and stroke

Ann Neurol

(1986)

F Mounier-Vehier et al.

Silent infarcts in patients with ischemic stroke are related to age and size of the left atrium

Stroke

(1993)

Echocardiographic predictors of stroke in patients with atrial fibrillation: a prospective study of 1066 patients from 3 clinical trials

Arch Intern Med

(1998)

CW Chiang et al.

Predictors of systemic embolism in patients with mitral stenosis: a prospective study

Ann Intern Med

(1998)

CK Friedberg

Diseases of the heart.

(1966)

AB Carter

Prognosis of cerebral embolism

Lancet

(1965)

GF Adams et al.

Cerebral embolism and mitral stenosis: survival with and without anticoagulants

J Neurol Neurosurg Psychiatry

(1974)

The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation

The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators

N Engl J Med

(1990)

Preliminary report of the Stroke Prevention in Atrial Fibrillation Study

N Engl J Med

(1990)

MD Ezekowitz et al.

Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators

N Engl J Med

(1992)

Cited by (362)

Between a rock and a hard place: resumption of oral anticoagulant therapy after intracranial hemorrhage
2024, Journal of Thrombosis and Haemostasis
Intracranial hemorrhage (ICH) is the most feared and lethal complication of oral anticoagulant (OAC) therapy. Resumption of OAC after ICH has long posed a challenge for clinicians, complicated by the expanding range of anticoagulant agents available in modern clinical practice, including direct OACs and, more recently, factor XI and XII inhibitors. A review of the current literature found support for resuming OAC in the majority of patients after ICH based on pooled retrospective data showing that resumption is associated with a lower risk of mortality and thromboembolism without a significantly increased risk of recurrent hemorrhage. The optimal time to resume OAC is less clear; however, the available evidence suggests that the composite risk of both recurrent hemorrhage and thromboembolism is likely minimized, somewhere between 4 and 6 weeks, after ICH in most patients. Specific considerations to guide the optimal resumption time in the individual patient include ICH location, mechanism, and anticoagulant class. Patients with mechanical heart valves and intracerebral malignancy represent high-risk groups who require more nuanced decision making. Here, we appraise the literature with the aim of providing a practical guide for clinicians while also discussing priorities for future investigation.
2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines
2024, Journal of the American College of Cardiology
The “2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Patients With Atrial Fibrillation” provides recommendations to guide clinicians in the treatment of patients with atrial fibrillation.
A comprehensive literature search was conducted from May 12, 2022, to November 3, 2022, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through November 2022, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate.
Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally. Recommendations from the “2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation” and the “2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation” have been updated with new evidence to guide clinicians. In addition, new recommendations addressing atrial fibrillation and thromboembolic risk assessment, anticoagulation, left atrial appendage occlusion, atrial fibrillation catheter or surgical ablation, and risk factor modification and atrial fibrillation prevention have been developed.
Left Atrial Thrombus—Are All Atria and Appendages Equal?
2023, Cardiac Electrophysiology Clinics
Cancer-associated non-bacterial thrombotic endocarditis
2022, Thrombosis Research
This paper reviews the current evidence on the pathogenesis, clinical manifestations, diagnosis and management of cancer-associated non-bacterial thrombotic endocarditis (NBTE). NBTE is an underdiagnosed condition characterized by sterile valvular vegetations composed of platelets and fibrin which are susceptible to systemic embolization. Cancer is a leading cause of NBTE and should be excluded in NBTE cases without a clear etiology. Malignancies most frequently associated with NBTE are mucin-releasing adenocarcinomas of the lung, ovary, biliary system, pancreas, breast and stomach. NBTE carries a high risk of arterial thromboembolism, while cardiac valvular dysfunction is much less frequent. NBTE appears to be an important underdiagnosed cause of cancer-associated embolic stroke of undetermined source. Characteristics associated with cancer-associated NBTE include elevated D-dimer, visceral infarcts, cerebral infarcts in multiple vascular territories, transcranial doppler microembolic signals, disseminated cancer and adenocarcinoma histology. Transesophageal echocardiography is the diagnostic test of choice, and all suspected cases should be evaluated for the presence of elevated D-dimers and disseminated intravascular coagulation. Long-term anticoagulation with low molecular weight heparin should be strongly considered, and surgical intervention is usually not needed. Underlying cancer must be diagnosed swiftly (if previously undiagnosed) and anti-cancer treatment should be initiated as soon as possible. The paucity of data regarding all aspects of NBTE, and the severe clinical consequences of untreated NBTE, are an urgent call for future research.
Left Atrial Thrombus—Are All Atria and Appendages Equal?
2022, Interventional Cardiology Clinics
Tissue engineering: Relevance to neonatal congenital heart disease
2022, Seminars in Fetal and Neonatal Medicine
Congenital heart disease (CHD) represents a large clinical burden, representing the most common cause of birth defect-related death in the newborn. The mainstay of treatment for CHD remains palliative surgery using prosthetic vascular grafts and valves. These devices have limited effectiveness in pediatric patients due to thrombosis, infection, limited endothelialization, and a lack of growth potential. Tissue engineering has shown promise in providing new solutions for pediatric CHD patients through the development of tissue engineered vascular grafts, heart patches, and heart valves. In this review, we examine the current surgical treatments for congenital heart disease and the research being conducted to create tissue engineered products for these patients. While much research remains to be done before tissue engineering becomes a mainstay of clinical treatment for CHD patients, developments have been progressing rapidly towards translation of tissue engineering devices to the clinic.

View all citing articles on Scopus

View full text