Guideline 36: Antithrombotic Therapy

Antithrombotic Therapy
Section 4: Other cardiac causes of systemic embolism

In patients in sinus rhythm, systemic emboli may arise from mural thrombi in the left atrium or left ventricle, from prosthetic valves, or from infected valves in bacterial endocarditis. High, moderate and low risk groups may be defined (see table 6). Echocardiography is helpful in defining risk, particularly in the diagnosis of dilated cardiomyopathy, valve abnormalities, intracardiac thrombus, and left atrial enlargement. As for non-valvular AF, prophylaxis is usually with warfarin for higher-risk patients, and with aspirin or no treatment for lower-risk patients. Intravenous heparin may be indicated in acute thrombosis (see section 6.2), or if warfarin has to be stopped, e.g. for elective surgery (see section 13.4). In high-risk patients, anticoagulants should be discontinued only if justified by emergencies. Anticoagulants should generally be avoided in patients with active bacterial endocarditis.

The evidence for thrombotic risk and for efficacy of antithrombotic therapy in patients with cardiac sources of systemic embolism has recently been reviewed in detail in consensus statements^{84,
85, 86} and is summarised here.

4.1 Rheumatic mitral valve disease

Well-conducted observational studies, extrapolation of randomised controlled studies in non rheumatic AF,⁸² and the recommendations of expert bodies^{84,
85, 86} indicate that warfarin prophylaxis is indicated in patients with rheumatic mitral valve disease (especially mitral stenosis), who have a high risk of systemic embolism. This risk increases in the presence of previous systemic embolism; atrial fibrillation; heart failure; or the presence of atrial thrombi, increased atrial size or possibly spontaneous echo contrast at echocardiography. Evidence level II, III and IV

Long-term warfarin prophylaxis (target INR 2.5, range 2.0-3.0) is recommended in patients with rheumatic mitral valve disease.

Long-term warfarin prophylaxis (target INR 2.5, range 2.0-3.0) is recommended in patients with rheumatic mitral stenosis with atrial fibrillation.

4.2 Mitral valve prolapse, mitral annular calcification, and isolated aortic valve disease

These patient groups appear to have a low risk of systemic embolism in the absence of previous systemic embolism or atrial fibrillation. Extrapolation of studies in non rheumatic AF and the recommendations of expert bodies^{84,
85, 86} indicate that warfarin prophylaxis is only indicated in the presence of previous systemic embolism or atrial fibrillation.

Long-term warfarin prophylaxis (target INR 2.5, range 2.0-3.0) is recommended for patients with mitral valve prolapse, mitral annular calcification, or isolated aortic valve disease only in the presence of previous systemic embolism or atrial fibrillation.

Table 6

Risk of systemic embolism in cardiac conditions other than atrial fibrillation

High risk

Rheumatic heart valve disease (especially mitral stenosis)

Prosthetic heart valves

mechanical
bioprosthetic, if:
- atrial fibrillation
- previous systemic embolism
- left atrial thrombus at surgery
- mitral, for first three months

Left ventricular mural thrombus

acute myocardial infarction (especially anterior Q wave)
left ventricular aneurysm

Moderate risk

Dilated cardiomyopathy
Non-rheumatic heart valve disease with atrial fibrillation
Congestive cardiac failure

Low risk

Uncomplicated acute myocardial infarction, other than large anterior Q-wave infarctions
Minor valve abnormalities in sinus rhythm
Hypertropic cardiomyopathy

The risk of embolism increases in the presence of atrial fibrillation or previous history of embolism

4.3 Cardiomyopathies and cardiac failure

Studies indicate that dilated cardiomyopathy and cardiac failure carry a risk of embolism of 2.0-2.4% per annum in the absence of previous systemic embolism or atrial fibrillation.⁸⁸

Hypertrophic cardiomyopathy carries a low embolic risk.

The benefits and risks of warfarin, aspirin or no antithrombotic therapy in cardiac failure with sinus rhythm are not well-established, and are currently being assessed in the Warfarin/Aspirin/Heart Failure (WASH) study. (See the SIGN guideline on Diagnosis and Treatment of Heart Failure due to Left Ventricular Systolic Dysfunction.⁸⁹)

Long-term warfarin prophylaxis (target INR 2.5, range 2.0-3.0) is recommended for patients with dilated cardiomyopathy or cardiac failure only in the presence of previous systemic embolism or atrial fibrillation.

4.4 Mechanical heart valves

Well-conducted observational studies show that patients with mechanical heart valves have a high risk of embolism which is reduced by long term oral anticoagulation.^{10,
11, 85,
86} Evidence level II, III and IV

Patients with mechanical heart valves should receive long-term prophylaxis with warfarin.

A target INR of 3.5, range 3.0-4.0, has traditionally been recommended for patients with mechanical heart valves and is appropriate for first generation valves (e.g. Starr-Edwards, Bjork Shiley standard).

More recent studies support a reduction in target INR to 3.0, range 2.5-3.5, for patients with second generation mechanical heart valves (e.g. St. Jude, Medtronic, Monostrut).^{85,
86}

The addition of aspirin (100 mg/day) reduced vascular mortality in one study,⁹⁰ but increased the risk of bleeding. Dipyridamole is also effective, without increased risk of bleeding.^{85, 86} Evidence level Ib

Addition of aspirin or dipyridamole should be considered in patients who suffer systemic embolism despite adequate-intensity warfarin. ⁸⁵

4.5 Bioprosthetic heart valves

Patients with bioprosthetic heart valves have a high risk of embolism if they have atrial fibrillation, a history of systemic embolism, evidence of left atrial thrombus at surgery, persistent left atrial enlargement, or persistent heart failure.^{85,
86}

Patients with bioprosthetic heart valves who have additional thrombotic risk factors should receive long term prophylaxis with warfarin (INR 2.5, range 2.0-3.0).

The addition of aspirin (100 mg/day) reduced vascular mortality in one study, but increased the risk of bleeding.⁹⁰ Evidence level Ib

Selected patients may receive aspirin as additional therapy.

Other patients with mitral bioprosthetic valves should receive:

warfarin for 3-6 months (target INR 2.5, range 2.0-3.0)

followed by long-term aspirin (300 mg/day).

In other patients with isolated aortic or tricuspid bioprosthetic valves, warfarin is recommended for three months only, in the absence of atrial fibrillation or a history of systemic embolism.

4.6 Reconstructive valve procedures

The recommendations of the European Consensus Statement should be consulted.⁸⁶

4.7 Pregnancy in patients with heart valve disease or prostheses

Guidance is available from expert consensus statements.^{6, 70,
84, 85,
86}