Mechanical and Bioprosthetic Heart Valves
In a prospective, randomized, open-label, positive-controlled study9 in 254 patients, the thromboembolic-free interval was found to be significantly greater in patients with mechanical prosthetic heart valves treated with warfarin alone compared with dipyridamole-aspirin (p < 0.005) and pentoxifylline-aspirin (p < 0.05) treated patients. Rates of thromboembolic events in these groups were 2.2, 8.6 and 7.9/100 patient years, respectively. Major bleeding rates were 2.5, 0.0 and 0.9/100 patient years, respectively.

In a prospective, open-label, clinical trial comparing moderate (INR 2.65) vs. high intensity (INR 9.0) warfarin therapies in 258 patients with mechanical prosthetic heart valves, thromboembolism occurred with similar frequency in the two groups (4.0 and 3.7 events/100 patient years, respectively). Major bleeding was more common in the high intensity group (2.1 events/100 patient years) vs. 0.95 events/100 patient years in the moderate intensity group.10

In a randomized trial in 210 patients comparing two intensities of warfarin therapy (INR 2.0 to 2.25 vs. INR 2.5 to 4.0) for a 3-month period following tissue heart valve replacement, thromboembolism occurred with similar frequency in the two groups (major embolic events 2% vs. 1.9%, respectively, and minor embolic events 10.8% vs. 10.2%, respectively). Major bleeding complications were more frequent with the higher intensity (major hemorrhages 4.6%) vs. none in the lower intensity.11

INDICATIONS AND USAGE
Warfarin sodium tablets are indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism.

Warfarin sodium tablets are indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement.

Warfarin sodium tablets are indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction.

CONTRAINDICATIONS
Anticoagulation is contraindicated in any localized or general physical condition or personal circumstance in which the hazard of hemorrhage might be greater than the potential clinical benefits of anticoagulation, such as:

Pregnancy: Warfarin sodium tablets are contraindicated in women who are or may become pregnant because the drug passes through the placental barrier and may cause fatal hemorrhage to the fetus in utero. Furthermore, there have been reports of birth malformations in children born to mothers who have been treated with warfarin during pregnancy.

Embryopathy characterized by nasal hypoplasia with or without stippled epiphyses (chondrodysplasia punctata) has been reported in pregnant women exposed to warfarin during the first trimester. Central nervous system abnormalities also have been reported, including dorsal midline dysplasia characterized by agenesis of the corpus callosum, Dandy-Walker ma