LOW-INTENSITY WARFARIN THERAPY

Background and Objective. Several studies comparing different intensit ies of oral anticoagulant treatment have clearly shown a relationship between bleeding complications and prolongation of prothrombin time. I n the early '50s, de Takats suggested that low-dose oral anticoagulant s 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(R) and Medline(R). Stat e of art and Perspectives. The hypothesis that low-dose oral anticoagu lants can be effective in preventing thrombosis was first proven by ex periments in animal models, and showed that a prothrombin time ratio a s low as 1.14 using rabbit brain thromboplastin was still able to conf er some inhibition of experimental thrombosis. Low-dose or very low-do se warfarin were subsequently demonstrated to be effective in patients with morbid obesity and decreased antithrombin III functional and ant igenic levels, in patients with indwelling catheters, in patients unde rgoing gynecological surgery, as well as in patients with stage IV bre ast cancer. Low-dose warfarin is also effective in the prevention of e mbolic strokes in patients with non-rheumatic atrial fibrillation. How ever, older patients (>75 years), who have a very high risk of bleedin g, might be safer taking a very low dose of warfarin (i.e., a daily do se of 1-1.25 mg). Moreover, after a period of run-in, a fixed, very lo w-dose warfarin schedule does not need further laboratory control, whi ch is a factor that could contribute to the full acceptance of treatme nt by patients and could stimulate a broader prescription of warfarin for the primary prevention of stroke in older patients with nonrheumat ic atrial fibrillation. Therefore, we have organized a multicenter cli nical trial in which 1000 patients with non-rheumatic atrial fibrillat ion will be randomized to receive either a fixed mini-dose of warfarin or a standard dose. Positive results might permit the treatment of mo st older patients with non-rheumatic atrial fibrillation, creating a b enefit for the community as a consequence of its effective prevention of disabling strokes. (C) 1997, Ferrata Storti Foundation.