Several studies comparing different intensities of oral
anticoagulant treatment have clearly shown a relationship between
bleeding complications and prolongation of prothrombin time. In the early '50s, de Takats suggested that low-dose oral
anticoagulants might be as effective as higher doses in preventing
thrombosis, at a lower risk of
bleeding. This review article examines the potential of low dose
warfarin therapy.
INFORMATION SOURCES: The authors have been working in this field, contributing original papers. In addition, the material examined in this article includes articles published in the journals covered by the Science Citation Index and MedLine.
STATE OF ART AND PERSPECTIVES: The hypothesis that low-dose oral
anticoagulants can be effective in preventing
thrombosis was first proven by experiments in animal models, and showed that a prothrombin time ratio as low as 1.14 using rabbit brain
thromboplastin was still able to confer some inhibition of experimental
thrombosis. Low-dose or very low-dose
warfarin were subsequently demonstrated to be effective in patients with
morbid obesity and decreased
antithrombin III functional and antigenic levels, in patients with
indwelling catheters, in patients undergoing
gynecological surgery, as well as in patients with stage IV
breast cancer. Low-dose
warfarin is also effective in the prevention of
embolic strokes in patients with non-rheumatic
atrial fibrillation. However, older patients (> 75 years), who have a very high risk of
bleeding, might be safer taking a very low dose of
warfarin (i.e., a daily dose of 1-1.25 mg). Moreover, after a period of run-in, a fixed, very low-dose
warfarin schedule does not need further laboratory control, which is
a factor that could contribute to the full acceptance of treatment by patients and could stimulate a broader prescription of
warfarin for the primary prevention of
stroke in older patients with nonrheumatic
atrial fibrillation. Therefore, we have organized a multicenter clinical trial in which 1000 patients with non-rheumatic
atrial fibrillation will be randomized to receive either a fixed mini-dose of
warfarin or a standard dose. Positive results might permit the treatment of most older patients with non-rheumatic
atrial fibrillation, creating a benefit for the community as a consequence of its effective prevention of disabling
strokes.