Recent issues on the initial phase of warfarin treatment [Attuali problemi nella fase iniziale dei trattamenti con warfarin]

Warfarin is the most commonly used vitamin K antagonist (VKA), based on its demonstrated efficacy in the prevention and treatment of venous and arterial thromboembolism. Optimal management of warfarin therapy is a daily challenge, mainly because of its complex pharmacokinetics and pharmacodynamics. In particular, the induction phase of warfarin treatment is unpredictable, thus placing patients to an increased risk of excessive anticoagulation, which predisposes to bleeding, or to prolonged subtherapeutic anticoagulation, which predisposes to thrombosis and often mandates extended therapy with parenteral anticoagulants. A number of algorithms has been developed to initiate warfarin therapy. Unfortunately, most have failed to gain widespread acceptance. In this review we briefly discuss the results of published clinical trials that assessed different initial approaches to warfarin therapy, their main findings and limitations. In summary, we can conclude that there is sufficient evidence to support the use of different starting doses of warfarin based on both individual and disease-specific factors. In particular, younger outpatients require higher starting doses of warfarin (7.5-10 mg) than older and hospitalized patients (2.5-5 mg), and than patients following cardiopulmonary by-pass surgery. However, further clinical studies are necessary to identify the best strategy to individualize warfarin initiation therapy.