[New perspectives for anticoagulation in non-rheumatic atrial fibrillation: oral antithrombins]

Non-rheumatic atrial fibrillation (NRAF) is one among the major public health problems, because it is associated with a high incidence of stroke or systemic thromboembolism. Warfarin significantly reduces cerebral/systemic events mainly in high-risk patients; unfortunately such drug is often as well under-used in eligible patients as under-dosed in treated patients. Traditional therapy with oral anticoagulants has several disadvatages: narrow therapeutic window, and often unpredictable dose-response so that frequent monitoring of the INR is required. It is therefore crucial that patients preferences and education be integrated into the decision-making process. Physicians often underprescribe oral anticoagulants since they perceive the risk of major bleeding as unacceptable because of some well known risk factors (e.g. previous bleedings, severe hypertension), and of qualms about drug interactions or alleged poor compliance. Therefore, the development of easy-to-use antithrombotic agents is still a challenge. New agents such as oral direct thrombin inhibitors are going to hold the promise for the next future. Ximelagatran is an orally active small molecule; being the first new oral anticoagulant used in large clinical trials. This molecule has many advantages in comparison to warfarin, such as the rapid onset/offset of action, the fixed oral dose, the no need of dose adjustment or of anticoagulation monitoring, as well the lack of food/alcohol intake interference as of drug interactions. The SPORTIF III and V trials have shown that ximelagatran is not inferior to warfarin in the prevention of strokes in patients with NRAF (both persistent and paroxysmal), but a side effect--consisting in the significant elevation of liver enzymes (> 3 times the upper limit of normal) in 6% of patients--was found. Further randomized trials are clearly needed, while current data suggest that ximelagatran will be able to represent a future viable therapeutic option for prevention of thromboembolism in patients with NRAF, offering huge advantages with respect to classic oral anticoagulants.