Ximelagatran (Exanta) - nové antikoagulans v léčbě fibrilace síní

Cor Vasa 2004, 45(12):582-586

Ximelagatran (Exanta) -a novel anticoagulant in the treatment of atrial fibrillation

Otto Mayer: Oddělení klinické farmakologie, Fakultní nemocnice Plzeň, Plzeň, Česká republika

Ximelagatran is a novel oral thrombin inhibitor. The therapeutic range of ximelagatran-unlike the commonly used warfarin-allows to use the former without laboratory monitoring of the anticoagulant effect. The present text is an overview of results of clinical trials designed to test the efficacy and safety of ximelagatran use in preventing central and peripheral embolic complications in atrial fibrillation.
SPORTIF (Stroke Prevention using an ORal Trombin Inhibitor in atrial Fibrillation) II was a "dose finding" trial demonstrating no significant difference in the effect of oral ximelagatran if administered twice a day over a range of 20-60 mg.
SPORTIF III was a multicenter trial conducted in a total of 3,407 patients with atrial fibrillation in a number of European centers. Ximelagatran was administered at a uniform dose of 36 mg twice a day (without anticoagulant effect monitoring) as against warfarin whose dose was (by contrast) adjusted to the International Normalized Ratio (INR). Two-year therapy revealed ximelagatran was not inferior to warfarin in its ability to prevent cerebral and periphery-related embolism while showing a comparable and relatively low tendency (less than 2%) to massive bleeding complications. As a result, the benefit is not ximelagatran's higher efficacy but the fact the same effect is accomplished without laboratory monitoring. The need to determine INR so the dose of warfarin can be regularly adjusted makes warfarin therapy fairly difficult. Under controlled conditions in SPORTIF trials, INR levels of 2-3 were only obtained in 60-80% of patients; the success rate in practice is substantially lower with its clinical implications.
SPORTIF V was conducted in the USA and, in terms of methodology, it only differed in the INR of warfarin set in the core laboratory (in Europe, INR was set locally). The trial included fewer than 4,000 patients, with average treatment duration of 18 months. It again showed that ximelagatran was not inferior to warfarin both in its desirable anticoagulant action (1.6% vs 1.2% embolic events) and in the incidence of undesirable bleeding episodes.
Investigators are still puzzled by the transient increases in circulating aminotransferase levels whose clinical relevance remains unclear (6% of ximelagatran-treated patients vs 1% of patients receiving warfarin).
Another series of trials referred to as THRIVE was designed to assess the antithrombotic efficacy of ximelagatran in secondary prevention and treatment of deep vein thrombosis with encouraging results. Ximelagatran has also been used with success in secondary prevention after myocardial infarction (ESTEEM trial).
Data emerging from trials with ximelagatran suggest the agent is a future alternative to warfarin with the additional plus no laboratory monitoring of the anticoagulant effect is required.