Warfarin is an oral anticoagulant drug, and remains the most widely used in its category. Its primary use is to prevent and treat venous thrombosis, and to prevent and stop the extension of clots. This is also the rationale for its use in atrial fibrillation.

Common indications

The most common indications for warfarin are:

• Prevention of deep vein thrombosis such as may occur following major gynecologic or hip surgery, which often causes prolonged immobilization. It is also sometimes associated with chemotherapy for some malignancies. An International Normalized Ratio (INR) of 2 to 3 with warfarin is usually sufficient. The duration of warfarin prophylaxis in such cases is usually three months.
• Treatment of venous thrombosis, whether spontaneous, recurrent or associated with risk factors, such as the antiphospholipid antibody syndrome or other thrombophilias. Proximal venous thrombosis, and recurrent thrombosis, warrant prolonged therapy for 6-12 months, while thrombosis secondary to thrombophilic conditions requires lifelong therapy.
• Prevention of pulmonary embolism is as above.
• Prevention of systemic embolism in atrial fibrillation, which predisposes to cardiac chamber thrombosis and embolic stroke, has been proved to occur to a significant extent with warfarin. Therapy is usually lifelong.
• Prevention of systemic embolism in mechanical heart valves which are prone to develop thrombosis seems to be a well-established benefit of warfarin, though with increased bleeding complications, when compared to antiplatelet drugs. Lifelong warfarin treatment is recommended, compared to three months of therapy with low-risk bioprosthetic valves.

Other indications

More doubtful indications include:

• Primary prevention of acute myocardial infarction in patients with peripheral arterial disease or other high-risk factors – trials have not provided unequivocal evidence of any significant benefit from the use of low-dose warfarin prophylaxis.
• More doubtful indications such as prevention of recurrent transient ischemic attacks, and repeated myocardial infarction, stroke, or death in patients with an acute myocardial infarction. The choice of aspirin alone seems to be preferable to aspirin in combination with low-, moderate- or high-intensity warfarin, when the treatment efficacy and incidence of bleeding complications are compared with the reduction in relative risk of these conditions.
• Prevention of systemic embolism in mitral stenosis with sinus rhythm, and atrial fibrillation associated with valvular heart disease
• Treatment of patients diagnosed to have systemic embolism because of a congenital heart defect such as patent foramen ovale, or other unknown cause.
• Prevention of systemic embolism in dilated cardiomyopathy.

In most situations, the dose of warfarin is adjusted in the individual patient to maintain an INR of 2 to 3. Warfarin dosage and maintenance is a problem because of its narrow threshold of safety and long half-life in circulation. This leads to a dose-response relationship which makes toxicity as well as ineffective treatment a frequent possibility. The aim of therapy is to make sure the patient receives the dose of warfarin that is the lowest possible to keep clots from forming or extending.

References

• http://www.aafp.org/afp/1999/0201/p635.html#sec-2
• https://www.health.qld.gov.au/publications/clinical-practice/guidelines-procedures/medicines/warfarin-guidelines.pdf
• http://circ.ahajournals.org/content/107/12/1692.full